Laparoscopic versus open total mesorectal excision for rectal cancer

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Authors


Abstract

Background

Colorectal cancer including rectal cancer is the third most common cause of cancer deaths in the western world. For colon carcinoma, laparoscopic surgery is proven to result in faster postoperative recovery, fewer complications and better cosmetic results with equal oncologic results. These short-term benefits are expected to be similar for laparoscopic rectal cancer surgery. However, the oncological safety of laparoscopic surgery for rectal cancer remained controversial due to the lack of definitive long-term results. Thus, the expected short-term benefits can only be of interest when oncological results are at least equal.

Objectives

To evaluate the differences in short- and long-term results after elective laparoscopic total mesorectal excision (LTME) for the resection of rectal cancer compared with open total mesorectal excision (OTME).

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013, Issue 2), MEDLINE (January 1990 to February 2013), EMBASE (January 1990 to February 2013), ClinicalTrials.gov (February 2013) and Current Controlled Trials (February 2013). We handsearched the reference lists of the included articles for missed studies.

Selection criteria

Only randomised controlled trials (RCTs) comparing LTME and OTME, reporting at least one of our outcome measures, was considered for inclusion.

Data collection and analysis

Two authors independently assessed study quality according to the CONSORT statement, and resolved disagreements by discussion. We rated the quality of the evidence using GRADE methods.

Main results

We identified 45 references out of 953 search results, of which 14 studies met the inclusion criteria involving 3528 rectal cancer patients. We did not consider the risk of bias of the included studies to have impacted on the quality of the evidence. Data were analysed according to an intention-to-treat principle with a mean conversion rate of 14.5% (range 0% to 35%) in the laparoscopic group.
There was moderate quality evidence that laparoscopic and open TME had similar effects on five-year disease-free survival (OR 1.02; 95% CI 0.76 to1.38, 4 studies, N = 943). The estimated effects of laparoscopic and open TME on local recurrence and overall survival were similar, although confidence intervals were wide, both with moderate quality evidence (local recurrence: OR 0.89; 95% CI 0.57 to1.39 and overall survival rate: OR 1.15; 95% CI 0.87 to1.52). There was moderate to high quality evidence that the number of resected lymph nodes and surgical margins were similar between the two groups.
For the short-term results, length of hospital stay was reduced by two days (95% CI -3.22 to -1.10), moderate quality evidence), and the time to first defecation was shorter in the LTME group (-0.86 days; 95% CI -1.17 to -0.54). There was moderate quality evidence that 30 days morbidity were similar in both groups (OR 0.94; 95% CI 0.8 to 1.1). There were fewer wound infections (OR 0.68; 95% CI 0.50 to 0.93) and fewer bleeding complications (OR 0.30; 95% CI 0.10 to 0.93) in the LTME group.
There was no clear evidence of any differences in quality of life after LTME or OTME regarding functional recovery, bladder and sexual function. The costs were higher for LTME with differences up to GBP 2000 for direct costs only.

Authors' conclusions

We have found moderate quality evidence that laparoscopic total mesorectal excision (TME) has similar effects to open TME on long term survival outcomes for the treatment of rectal cancer. The quality of the evidence was downgraded due to imprecision and further research could impact on our confidence in this result. There is moderate quality evidence that it leads to better short-term post-surgical outcomes in terms of recovery for non-locally advanced rectal cancer. Currently results are consistent in showing a similar disease-free survival and overall survival, and for recurrences after at least three years and up to 10 years, although due to imprecision we cannot rule out superiority of either approach. We await long-term data from a number of ongoing and recently completed studies to contribute to a more robust analysis of long-term disease free, overall survival and local recurrence.

摘要

對於大腸癌,腹腔鏡和全繫膜切除的手術比較

背景

在西方世界,大腸癌(包括直腸癌)是第三個常見的癌症死亡原因。對於結腸癌,腹腔鏡手術被證實,術後恢復快、併發症少,並在外觀上更美觀同時也達到癌症細胞切除效果。這些短期利益如預期中的和腹腔鏡直腸癌手術相似。然而,腹腔鏡手術的腫瘤安全性在直腸癌仍然有爭議,由於缺乏長期明確的結果。因此,至少在腫瘤結果一樣的情況下,短期預期的優點只能是當作附加的優勢。

目的

評估選擇腹腔鏡全直腸系膜切除術(laparoscopic total mesorectal excision)和開放的全直腸系膜切除術(open total mesorectal excision),其在短期和長期結果的差異。

搜尋策略

我們搜尋了 Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013年第二期), MEDLINE (從1990年ㄧ月到2013年二月), EMBASE (1990年ㄧ月到2013年二月),ClinicalTrials.gov( 2013年二月) 和Current Controlled Trials( 2013年二月). 我們用人工搜尋參考資料的清單,其中包含所遺漏的研究。

選擇標準

只有比較腹腔鏡全直腸系膜切除術(Laparoscopic total mesorectal excision)和開放的全直腸系膜切除術(open total mesorectal excision)的隨機對照試驗(randomised controlled trials,RCTs),至少有一個試驗結果包含在結論中。

資料收集與分析

二位獨立作者評估研究的品質,依照CONSORT的狀態和透討論解決不同意見的方式。我們透過GRADE方法評值證據的等級。

主要結果

我們確定45個參考資料,其中有953的搜索結果,有14項研究符合,包括3528位直腸癌患者符合標準。我們沒有將會影響研究品質的偏差結果納入研究的考量中。腹腔鏡組別中,研究數據會根據意向性治療的平均轉化率原則來分析,數值為14.5%(範圍從0%至35%)。
中等質量的證據顯示,腹腔鏡和開放的全直腸繫膜切除,在五年無復發生存率相似的結果(勝算比 1.02; 95%信賴區間0.76 to 1.38,4項研究中,樣本數 = 943)。評估腹腔鏡和開放的全直腸繫膜切除術在局部復發和整體生存的結果是相似的,但可信區間寬在中等質量的證據二組是相似(局部復發:勝算率0.89; 95%信賴區間 0.57 到1.39和整體總生存率:勝算率1.15; 95%信賴區間為0.87 到1.52)。有中等到高品質的證據顯示,切除的淋巴結的數目和外科手術的邊界在腹腔鏡和開放的全直腸繫膜切除術二組中有類似的結果。
對於短期結果,住院天數減少兩天(95%信賴區間為-3.22至-1.10),中等品質的證據),以及首次排便時間在腹腔鏡全直腸系膜切除術組別中,明顯縮短(-0.86天; 95 %信賴區間為-1.17至-0.54)。有中等質量的證據表明,30天發病率在兩組當中是相似(勝算率 0.94; 95%信賴區間為0.8〜1.1)。在腹腔鏡全直腸繫膜切除組別中,有較少的傷口感染(勝算率 0.68; 95%信賴區間為0.50〜0.93)和更少的出血併發症(勝算率 0.30; 95%信賴區間為0.10〜0.93)。
二組之間的生活品質,不論是在日常生活功能的恢復或是膀胱和性功能方面,沒有明顯得證據顯著不同。在成本分析上,腹腔鏡全繫膜切除術高達GBP 2000。

作者結論

我們發現中等品質的證據顯示,腹腔鏡全直腸系膜切除術具有和開方的全直腸繫膜切開術,在長期生存結果上有類似的治療效果對直腸癌。證據的質量被降級,由於不精確和進一步研究不能增加在結論上的信心。中等質量的證據顯示,對於局部非晚期直腸癌,在外科手術過後有更好的復原效果。目前的結果是呈現出類似的無復發的生存期和總生存期,而且在三年或是10年復發上也是一致的,但由於不準確,我們不能排除這兩種方法的優勢。有數個正在進行或是最近完成的研究,在長期無復發情況或是整體生存存活率上,期待未來有更多的數據和更力的分析。

譯註

翻譯者:臺北醫學大學考科藍臺灣研究中心(Cochrane Taiwan)

本翻譯計畫由臺北醫學大學考科藍臺灣研究中心(Cochrane Taiwan)、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行
聯絡E-mail:cochranetaiwan@tmu.edu.tw

Résumé scientifique

Excision mésorectale totale par technique laparoscopique versus ouverte dans le cancer rectal

Contexte

Le cancer colorectal, y compris le cancer rectal, est la troisième cause la plus fréquente de décès par cancer dans le monde occidental. Pour le carcinome du côlon, il a été démontré que la chirurgie laparoscopique résultait en une récupération postopératoire plus rapide, moins de complications et de meilleurs résultats esthétiques, pour des résultats oncologiques équivalents. Ces bénéfices à court terme sont supposés être similaires pour la chirurgie laparoscopique du cancer rectal. Cependant, l'innocuité oncologique de la chirurgie laparoscopique pour un cancer rectal est resté controversée en raison du manque de résultats définitifs à long terme. Par conséquent, les bénéfices attendus à court terme ne peuvent avoir d'intérêt que si les résultats oncologiques sont au moins équivalents.

Objectifs

Évaluer les différences de résultats à court et à long terme après l'excision mésorectale totale laparoscopique (EMTL) élective pour la résection du cancer rectal par rapport à l'excision mésorectale totale ouverte (EMTO).

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre Cochrane des essais contrôlés (CENTRAL, Bibliothèque Cochrane 2013, numéro 2), MEDLINE (de janvier 1990 à février 2013), EMBASE (de janvier 1990 à février 2013), ClinicalTrials.gov (février 2013) et Current Controlled Trials (février 2013). Nous avons effectué une recherche manuelle dans les références bibliographiques des articles inclus pour des études que nous aurions manquées.

Critères de sélection

Seuls les essais contrôlés randomisés (ECR) comparant l'EMTL et l'EMTO et rapportant au moins l'un de nos critères de jugement ont été pris en compte pour l'inclusion.

Recueil et analyse des données

Deux auteurs ont évalué la qualité des études de manière indépendante conformément à la déclaration CONSORT, et résolu les désaccords par discussion. Nous avons évalué la qualité des données au moyen de la méthode GRADE.

Résultats principaux

Nous avons identifié 45 références sur 953 résultats de recherche, dont 14 études remplissaient les critères d'inclusion, portant sur 3 528 patients atteints d'un cancer rectal. Nous avons considéré que le risque de biais des études incluses n'avait pas eu d'impact sur la qualité des preuves. Les données ont été analysées selon le principe de l'intention de traiter avec un taux de conversion moyen de 14,5 % (fourchette de 0 % à 35 %) dans le groupe laparoscopique.
Il y avait des preuves de qualité modérée indiquant que la laparoscopie et l'EMT ouverte présentaient des effets similaires sur la survie sans récidive à cinq ans (RC 1,02 ; IC à 95 % de 0,76 à 1,38 ; 4 études, N = 943). Les effets estimés de l'EMT laparoscopique et ouverte sur la récidive locale et la survie globale étaient similaires, mais les intervalles de confiance étaient larges, les deux avec des preuves de qualité modérée (récidive locale : RC 0,89 ; IC à 95 % de 0,57 à 1,39 et taux de survie globale : RC 1,15 ; IC à 95 % de 0,87 à 1,52). Il y avait des preuves de qualité modérée à élevée que le nombre de ganglions lymphatiques réséqués et les marges chirurgicales étaient similaires entre les deux groupes.
Pour les résultats à court terme, la durée de séjour à l'hôpital a été réduite de deux jours (IC à 95 % de -3,22 à -1,10 ; preuves de qualité modérée) et le temps avant la première défécation était plus courte dans le groupe EMTL (-0,86 jours ; IC à 95 % de -1,17 à -0,54). Il y avait des preuves de qualité modérée que la morbidité à 30 jours était similaire dans les deux groupes (RC 0,94 ; IC à 95 % de 0,8 à 1,1). Il y avait moins d'infections des plaies (RC 0,68 ; IC à 95 % de 0,50 à 0,93) et moins de complications hémorragiques (RC 0,30 ; IC à 95 % de 0,10 à 0,93) dans le groupe EMTL.
Il n'y avait aucune preuve solide de différence dans la qualité de vie après l'EMTL ou l'EMTO concernant la récupération fonctionnelle, la vessie et la fonction sexuelle. Les coûts étaient plus élevés pour l'EMTL, avec des différences jusqu'à 2 000 GBP pour les coûts directs uniquement.

Conclusions des auteurs

Nous avons trouvé des preuves de qualité modérée indiquant que l'excision mésorectale totale (EMT) laparoscopique a des effets similaires à l'EMT ouverte sur les résultats de survie à long terme pour le traitement d'un cancer rectal. La qualité des preuves a été abaissée en raison de l'imprécision et les futures recherches pourraient avoir un impact sur notre confiance dans ce résultat. Il existe des preuves de qualité modérée indiquant qu'elle entraîne de meilleurs résultats postopératoires à court terme en termes de rétablissement pour un cancer rectal qui n'est pas localement avancé. Actuellement les résultats sont cohérents en montrant une survie sans récidive et une survie globale similaires, ainsi que pour les récidives après au moins trois ans et jusqu'à 10 ans, mais en raison de l'imprécision nous ne pouvons pas exclure la supériorité de l'une ou l'autre approche. Nous attendons les données à long terme issues d'un certain nombre d'études en cours ou récemment achevées pour contribuer à une analyse plus robuste de la survie sans récidive à long terme, de la survie globale et de la récidive locale.

Plain language summary

Keyhole laparoscopic or open surgery for rectal cancer

Colorectal (large bowel) cancer including rectal cancer is the third most common cause of cancer deaths in the western world. The risk of developing rectal cancer increases with age and is most common in people around 70 years of age. The treatment consists of complete surgical resection of the tumour and surrounding tissue by a technique called total mesorectal excision (TME), sometimes combined with chemotherapy and radiotherapy. This surgery can be performed by either normal open abdominal surgery with a large incision or by keyhole laparoscopic surgery with several small incisions for the instruments and camera. For colon cancer, laparoscopic surgery is proven to result in faster postoperative recovery, fewer complications and better cosmetic results. These results are expected to be equal for rectal surgery. However, surgery for rectal cancer is technically more difficult than for colon cancer due to the location deeper in the pelvis and close to important nerves. Therefore a complete and safe resection of the tumour should be guaranteed, this is important to reduce the risk of recurrence of the tumour and could be tested by assessing recurrence rates and patient survival in the long term.

In this updated review, we have assessed all randomised studies of laparoscopic and open TME for rectal cancer, to compare and combine their results. We included 14 trials reporting on a total of 3528 patients undergoing rectal cancer surgery. In 14.5% of those having laparoscopic surgery needed conversion to open surgery by a large incision in the abdomen due to difficulties or problems during the procedure.

There is currently moderate quality evidence that laparoscopic total mesorectal excision (LTME) has similar effects to open TME (OTME) on long term survival outcomes for the treatment of rectal cancer. The estimated effect was imprecise and further research could impact on our confidence int this result. There is moderate quality evidence that it leads to better short-term post-surgical outcomes in terms of length of hospital stay. We found that pain was lower in the LTME group and that resumption of diet was better. We did not find clear evidence of a difference in quality of life between the two groups, but costs were higher for LTME. We await long-term data from a number of ongoing and recently completed studies to contribute to our understanding of the effects of these surgical approaches on long-term disease free, overall survival and local recurrence.

淺顯易懂的口語結論

對於直腸癌,採用腹腔鏡或是傳統的開刀手術

大腸癌是西方世界排名第三最常見致死的癌症死亡原因。直腸癌隨著年齡的增長而增加其風險,常見於70歲左右年齡的族群。治療方式,包含外科手術切除腫瘤本身和其周圍的組織,稱之為全直腸系膜切除術。有時輔以化學治療和放射線治療。這種手術可以是,傳統的大切口開腹手術或是鎖孔式腹腔鏡手術,使用幾個小切口的儀器和攝影機進行。對於結腸癌,腹腔鏡手術被證明,術後恢復快、併發症少和更美觀的皮膚外觀。以上這一些結果是被預期和傳統外科手術有一樣的效果。但是,由於腸子是在骨盆深層且靠近重要的神經,傳統的外科手術對於切除直腸癌是有技術上的困難。因此一個完整與安全的腫瘤切除應該需要被保證,減少腫瘤復發的風險是很重要的,並且可透過評估長期的復發率和患者存活率來驗證。

在這最新審查報告,我們評估了腹腔鏡全直腸繫膜手術和開放的全直腸係膜直腸癌手術,其相關的所有隨機研究,進而去比較和結合其研究結果。我們包括14項試驗,一共有3528位患者接受直腸癌手術。由於在手術當中的困難度,其中有14.5%的腹腔鏡病人需要接受傳統的外科手術。

目前中等質量的證據表明,腹腔鏡全直腸系膜切除術和開放的全直腸系膜切除術的長期生存結果對於直腸癌的治療有其類似的效果。在預估治療效果上不是很精準,進一步的研究可能會增加對於結果信心。有中等品質證據顯示,腹腔鏡在手術後,關於住院天數方面有較好的短期效果。 我們發現在腹腔鏡組在低疼痛和恢復飲食有較好的表現,然而在生活品質方面沒有明確證據顯示有所差異。但,腹腔鏡有較高的成本。我們期待一些正在進行的研究或是和最近已完成的研究之數據,以期能透過長期的數據更加了解手術對於長期無疾病、總生存率和局部復發的影響。

譯註

翻譯者:臺北醫學大學考科藍臺灣研究中心(Cochrane Taiwan)

本翻譯計畫由臺北醫學大學考科藍臺灣研究中心(Cochrane Taiwan)、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行
聯絡E-mail:cochranetaiwan@tmu.edu.tw

Résumé simplifié

Chirurgie laparoscopique mini-invasive ou chirurgie ouverte pour un cancer rectal

Le cancer colorectal (gros intestin), y compris le cancer rectal, est la troisième cause la plus fréquente de décès par cancer dans le monde occidental. Le risque de développer un cancer rectal augmente avec l'âge et est le plus fréquent chez les personnes autour de 70 ans. Le traitement consiste en une résection chirurgicale complète de la tumeur et des tissus environnants par une technique appelée excision mésorectale totale (EMT), parfois combinée à la chimiothérapie et à la radiothérapie. Cette chirurgie peut être réalisée soit par une chirurgie abdominale ouverte normale avec une grande incision ou par chirurgie laparoscopique mini-invasive avec plusieurs petites incisions pour les instruments et la caméra. Pour le cancer du côlon, il a été démontré que la chirurgie laparoscopique résultait en une récupération postopératoire plus rapide, moins de complications et de meilleurs résultats esthétiques. Ces résultats sont supposés être identiques pour la chirurgie rectale. Cependant, la chirurgie pour un cancer rectal est techniquement plus difficile que pour le cancer du côlon à cause de l'emplacement plus profondément dans le bassin, à proximité de nerfs importants. Par conséquent, la résection complète de la tumeur en toute sécurité doit être garantie. Cela est important pour réduire le risque de récidive de la tumeur et pourrait être vérifié en évaluant les taux de récidive et la survie des patients à long terme.

Dans cette revue mise à jour, nous avons évalué toutes les études randomisées sur l'EMT laparoscopique et ouverte pour un cancer rectal, afin de comparer et combiner leurs résultats. Nous avons inclus 14 essais portant sur un total de 3 528 patients subissant une opération du cancer rectal. Chez 14,5 % des patients traités par la chirurgie laparoscopique, il a été nécessaire de convertir l'opération en chirurgie ouverte par une grande incision dans l'abdomen en raison de difficultés ou de problèmes au cours de la procédure.

Il existe actuellement des preuves de qualité modérée indiquant que l'excision mésorectale totale laparoscopique (EMTL) a des effets similaires à ceux de l'EMT ouverte (EMTO) sur les résultats de survie à long terme pour le traitement d'un cancer rectal. L'effet estimé était imprécis et des recherches supplémentaires pourraient avoir un impact sur notre confiance en ce résultat. Il existe des preuves de qualité modérée indiquant qu'elle entraîne de meilleurs résultats postopératoires à court terme en termes de durée de séjour à l'hôpital. Nous avons trouvé que la douleur était plus faible dans le groupe EMTL et que la reprise du régime alimentaire était plus efficace. Nous n'avons pas trouvé de preuve claire d'une différence en termes de qualité de vie entre les deux groupes, mais les coûts étaient plus élevés pour l'EMTL. Nous attendons les données à long terme issues d'un certain nombre d'études en cours ou récemment achevées pour contribuer à notre compréhension des effets de ces approches chirurgicales sur la survie sans récidive à long terme, la survie globale et la récidive locale.

Notes de traduction

Traduit par: French Cochrane Centre 22nd July, 2014
Traduction financée par: Financeurs pour le Canada : Instituts de Recherche en Santé du Canada, Ministère de la Santé et des Services Sociaux du Québec, Fonds de recherche du Québec-Santé et Institut National d'Excellence en Santé et en Services Sociaux; pour la France : Ministère en charge de la Santé

Streszczenie prostym językiem

Operacje laparoskopowe czy chirurgia otwarta w leczeniu chorych na raka odbytnicy

Rak jelita grubego (w tym rak odbytnicy) jest trzecią co do częstości przyczyną zgonów z powodu nowotworów złośliwych w świecie zachodnim. Ryzyko zachorowania na raka odbytnicy zwiększa się z wiekiem i jest największe u osób około 70 roku życia. Leczenie składa się z całkowitej resekcji guza i otaczającej go tkanki za pomocą techniki zwanej całkowitym wycięciem mezorektum (TME), niekiedy połączonej z chemioterapią i radioterapią. Zabieg operacyjny może być wykonany zarówno poprzez otwarte dojście do jamy brzusznej z dużym rozcięciem powłok brzusznych lub przez kilka małych nacięć umożliwiających wprowadzenie do brzucha narzędzi laparoskopowych i kamery. W przypadku raka okrężnicy udowodniono, że zabiegi laparoskopowe umożliwiają szybszą rekonwalescencję, są obarczone mniejszym ryzykiem powikłań i dają lepszy efekt kosmetyczny. Podobnych wyników oczekuje się dla chirurgii odbytnicy. Jednakże ze względu na położenie w dnie miednicy i bliskość ważnych struktur nerwowych, chirurgia raka odbytnicy jest technicznie trudniejsza niż chirurgia raka okrężnicy. Niezbędne jest zatem zapewnienie całkowitej i bezpiecznej resekcji guza. Jest to ważne aby zmniejszyć ryzyko wystąpienia nawrotu nowotworu. Jakość resekcji może ocenić poprzez analizę częstości nawrotów choroby i długookresowego przeżycia chorych.

W tym zaktualizowanym przeglądzie, w celu porównania wyników leczenia oceniliśmy wszystkie badania z randomizacją dotyczące techniki laparoskopowej i otwartej TME u chorych na raka odbytnicy. Do przeglądu włączono 14 badań, w których oceniano wyniki leczenia 3528 pacjentów poddanych zabiegom chirurgicznym z powodu raka odbytnicy. Wśród chorych operowanych laparoskopowo, ze względu na trudności w trakcie zabiegu konieczne było wykonanie konwersji do zabiegu otwartego poprzez duże nacięcie powłok jamy brzusznej u 14,5% pacjentów.

Obecnie dysponujemy umiarkowanej jakości danymi, wskazującymi że laparoskopowe totalne wycięcie mezorektum (LTME) cechuje się podobnymi przeżyciami odległymi jak otwarte TME (OTME) w leczeniu raka odbytnicy. Szacowany efekt był nieprecyzyjny, a dalsze badania mogą wpłynąć na naszą pewność co do tego wyniku. Dysponujemy umiarkowanej jakości danymi, że LTME pozwala na osiągnięcie lepszych krótkoterminowych wyników okołooperacyjnych w zakresie długości pobytu w szpitalu. Stwierdziliśmy, że w grupie chorych po zabiegu LTME nasilenie bólu było mniejsze a powrót do odżywiania doustnego szybszy. Nie znaleźliśmy przekonujących dowodów świadczących o różnicy w jakości życia pomiędzy dwiema grupami. Koszty leczenia były większe dla grupy LTME. Czekamy na wyniki odległe wielu trwających i niedawno zakończonych badań. Mogą one przyczynić się do lepszego zrozumienia wpływu tych procedur chirurgicznych na odległe przeżycia wolne od objawów choroby, przeżycia całkowite i ryzyko wystąpienia wznowy miejscowej.

Uwagi do tłumaczenia

Tłumaczenie: Jerzy W. Mituś, Redakcja: Andrzej L. Komorowski

Summary of findings(Explanation)

Summary of findings for the main comparison. Laparoscopic versus open total mesorectal excision for rectal cancer
Laparoscopic versus open total mesorectal excision (TME) for rectal cancer
Patient or population: people with Rectal Cancer
Settings:
Intervention: Laparoscopic TME
Comparison: Open TME
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Assumed riskCorresponding risk
Open TME Laparoscopic TME
Disease-free survival at 5 years 718 per 1000 722 per 1000
(659 to 778)
OR 1.02
(0.76 to 1.38)
943
(4 studies)
⊕⊕⊕⊝
moderate 1
Overall survival at 5 years 679 per 1000 709 per 1000
(648 to 763)
OR 1.15
(0.87 to 1.52)
987
(4 studies)
⊕⊕⊕⊝
moderate 2
Local recurrences 54 per 1000 48 per 1000
(31 to 73)
OR 0.89
(0.57 to 1.39)
1538
(8 studies)
⊕⊕⊕⊝
moderate 3
Lymph nodes retrieved The mean number of lymph nodes retrieved in the intervention groups was
0.43 lower
(1.13 lower to 0.26 higher)
 3682
(11 studies)
⊕⊕⊕⊕
high
CRM positivity 61 per 1000 60 per 1000
(44 to 83)
OR 0.99
(0.71 to 1.4)
2313
(8 studies)
⊕⊕⊕⊝
moderate 4
30-day morbidity (total) 275 per 1000 263 per 1000
(233 to 295)
OR 0.94
(0.8 to 1.1)
3397
(11 studies)
⊕⊕⊕⊝
moderate 5
Hospital stay (days) The mean length of hospital stay in the intervention groups was
2.16 days shorter
(3.22 to 1.1 days shorter)
 3084
(11 studies)
⊕⊕⊕⊝
moderate 6
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio;
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Statistical inaccuracy with wide confidence interval at both sides

2Statistical inaccuracy with wide confidence interval at both sides, but a tendency for a higher overall survival for LTME

3Statistical inaccuracy with wide confidence interval at both sides, but a tendency for a lower recurrence rate for LTME

4Only 8 studies provided data on CRM positivity
5Definition of overall morbidity varied or was unclear
6Length of hospital stay depends on postoperative protocols and implementation of enhanced recovery programmes

Background

Description of the condition

The incidence of rectal cancer in the western world is 28% to 35% of the total colorectal cancer incidence, with 15 to 25/100,000 new patients per year for both men and women. The risk increases with age, with a median age of 70 years at the time of diagnosis; the associated mortality is between 4 and 10 per 100,000 per year (Glimelius 2013). Symptoms suggesting rectal cancer typically include changes in bowel habits, the feeling of incomplete emptying, rectal bleeding, anaemia or weight loss. The diagnosis can be made by tumour biopsy during colonoscopy or sigmoidoscopy. If rectal cancer is confirmed, the extent of the disease is examined by imaging of the chest and liver for signs of metastases, and magnetic resonance imaging (MRI) of the pelvis and/or endorectal ultrasound (ERUS) are done to determine the degree of rectal wall and mesorectal fascia invasion. The majority of rectal carcinomas are adenocarcinoma (95% to 98%), usually arising from an adenoma (Glimelius 2013; Monson 2013).

Description of the intervention

Complete resection of rectal cancer can be achieved by a sphincter-preserving anterior resection (AR, rectosigmoid resection) or an abdominoperineal resection (APR). Both had high local recurrence rates until the introduction of the total mesorectal excision (TME) (Heald 1986). Total mesorectal excision achieves a complete removal of the rectum together with its draining lymphatics, and results in low rates of recurrence. Despite the successful introduction of laparoscopic and laparoscopic-assisted procedures for the resection of colonic cancer, surgeons have been more reluctant to introduce laparoscopic TME due to the technically demanding resection plane.

How the intervention might work

Laparoscopic and laparoscopic-assisted TME offers several theoretical advantages compared to open resection. It may be associated with less blood loss, faster recovery, early feeding and a lower morbidity rate, as shown in laparoscopic colonic surgery (Braga 2002; Pikarsky 2002). The magnified view of the pelvis afforded by the laparoscope may facilitate identification of the autonomic nerves and thus prevent unintentional injury of these nerves. However, these advantages of LTME are only beneficial to people with rectal cancer when local recurrence and disease-free survival rates are at least similar to those achieved with OTME.

Why it is important to do this review

The introduction of laparoscopy 20 years ago has caused major changes in colorectal surgery. For benign disease, such as diverticulitis and inflammatory bowel disease, laparoscopy has become the surgical technique of choice for its benefits in recovery, complication rate and cosmetic results. Only recently, sufficient evidence has become available showing laparoscopic surgery is safe for the treatment of colonic cancer. Four large randomised trials (472 to 1076 participants) could not show any differences in quality of resection and long-term recurrence and survival rates between laparoscopic and open surgery for colon cancer (MRC CLASICC a 2005; COST 2007; COLOR 2009; LAPKON II 2009). Although COLOR 2009 was not able to rule out any difference with their non-inferiority design, the meta-analysis by Kuhry 2008 did not show any differences.

Despite the larger number of randomised trials on laparoscopic surgery for colon cancer, there is still limited evidence for long- and short-term outcomes after LTME due to the lack of high quality randomised controlled trials with sufficient follow up. Now the results of more well designed large randomised controlled trials (RCTs) become available, there is a need for a updated systematic review of these results.

Objectives

To evaluate the differences in short- and long-term results after elective laparoscopic total mesorectal excision (LTME) for the resection of rectal cancer compared with open total mesorectal excision (OTME).

Methods

Criteria for considering studies for this review

Types of studies

In contrast to the published protocol and previous version of this review, for this update we have only considered RCTs comparing LTME to OTME, since sufficient RCTs have become available since the publication of the original review. We did not apply any language restrictions.

Types of participants

People with rectal cancer undergoing total mesorectal excision were considered for inclusion. Studies including participants with colorectal cancer are only eligible if the results for those with rectal carcinoma were presented separately.

Types of interventions

These include laparoscopic, laparoscopic-assisted or open total mesorectal excision as (low) anterior resection or abdominoperineal resection. When a primary anastomosis was constructed, it could either be performed intraperitoneally ('double-stapled' colorectal anastomosis) or extraperitoneally (hand-sewn or stapled colorectal anastomosis).

Types of outcome measures

We sought the following outcomes in all included studies:

Primary outcomes

- Disease-free and overall survival

Secondary outcomes

- Recurrences (local, wound/port site and distant)
- Quality of resection (circumferential margin (CRM) positivity and number of lymph nodes)
- Surgical data (surgical time, incision length, conversion rate)
- Intraoperative complications, blood loss and transfusion requirement
- Postoperative morbidity and mortality (overall morbidity, need for reoperation, anastomotic leakage, wound infection, urinary complications, bleeding, chest infection)
- Postoperative pain (use of medication and visual analogue scale (VAS) score)
- Gastrointestinal recovery and hospital stay (time to first bowel movement, time to normal diet, length of hospital stay)
- Long-term morbidity (incisional herniae and bowel obstruction)
- Quality of life (functional recovery, bladder and sexual function)
- Immunologic response
- Costs

Search methods for identification of studies

Electronic searches

We followed the recommendations of the Cochrane Colorectal Cancer Group and searched the following bibliographic databases with no language restrictions in order to identify relevant primary studies:

Cochrane Central Register of Controlled Trials (CENTRAL) (January 1990 to February 2013);
MEDLINE (January 1990 to February 2013);
EMBASE (January 1990 to February 2013).

We conducted searches using medical subject headings (MeSH) and free-text words. The search has been adapted for each database search and is shown in Appendix 1 (CENTRAL), Appendix 2 (MEDLINE) and Appendix 3 (EMBASE).

Searching other resources

We handsearched the reference lists of all selected articles for further relevant studies. There was no language restriction. In addition, we searched for ongoing trials in the ClinicalTrials.gov and the Current Controlled Trials databases.

Data collection and analysis

Selection of studies

Two authors (SV and LP) independently reviewed all abstracts. We retrieved full-text copies of all studies that potentially met the inclusion criteria based on abstract review. If both authors agreed that a study did not meet the eligibility criteria, we excluded it. If we disagreed, we resolved conflicts by discussion and consensus or by consulting a third member of the review team.

Data extraction and management

We collected data according to the outcomes mentioned above. Each author extracted the data independently from each study and compared them, resolving disagreement by discussion. We used Review Manager 5 (RevMan 5.2) software for statistical analysis, provided by the Cochrane Collaboration. Data not suitable for meta-analysis is discussed in the results section.

Assessment of risk of bias in included studies

Two authors (SV and LP) have assessed all the selected studies for methodological quality according to the CONSORT Statement 2010, and have summarised the information in the 'Risk of bias' figure (Figure 2). In addition, we have used the Cochrane 'Risk of bias' tool as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Measures of treatment effect

We measured the treatment effect using the mean difference (MD) or standardised mean difference (SMD) for continuous data and the odds ratio (OR) for dichotomous data. Standardised mean differences were only used when the reported units or drugs varied between the studies, for instance the number of doses of analgesia. All outcomes included 95% confidence intervals (CI).

Unit of analysis issues

For randomised controlled trials for this surgical intervention, we would expect only a simple parallel design. The only possible cross-over would be the conversion of laparoscopy to open surgery. Because worse outcomes for this group can be expected and should be evaluated as a complication of laparoscopic-intended surgery, all analyses should be performed on the intention-to-treat principle.

Dealing with missing data

To avoid missing unpublished studies, we searched clinical trial databases as stated above. We compared reported outcomes to published protocols or to the Methods section of each article. If we found inconsistencies, this is reported in the 'Selective reporting' section of the 'Risk of bias' table. As missing postoperative and follow-up data are common in surgical studies, we assume a random pattern of missingness.

Assessment of heterogeneity

We used the Cochrane Chi² test (Q-test) to assess heterogeneity and the I² statistic to estimate the degree of heterogeneity (Higgins 2003). We considered an I² of between 0% and 40% as probably not important, between 30% and 60% as representing moderate heterogeneity, between 50% and 90% as substantial heterogeneity, and between 75% and 100% as considerable heterogeneity (Higgins 2011). We used a fixed-effect analysis for outcomes with low heterogeneity.

Assessment of reporting biases

We present an overview of all outcomes per study in the table Selective reporting (reporting bias).

Data synthesis

We analysed continuous variables using mean differences with 95% confidence intervals. For dichotomous variables we used odds ratios with 95% confidence intervals. We constructed forest plots, using the Mantel-Haenszel method (fixed- or random-effects) to combine the outcomes. In case of continuous data presented as median and range, we estimated the mean and standard deviation according to the methods described by Hozo 2005. We generated funnel plots to screen for publication bias. In case of inclusion of an original RCT and the additional publication of a subgroup of participants, we included only the most appropriate subgroup data in the meta-analyses, to avoid duplication of data.

Subgroup analysis and investigation of heterogeneity

We had planned subgroup analyses for abdominoperineal resection (APR) and anterior resection (AR), and for studies allowing and excluding neoadjuvant therapy. These analyses were not performed because too few studies presented separate data for these groups. However, we plan to explore these subgroups if possible in future updates.

Summary of Findings table

We applied methods developed by the GRADE working group to rate the quality of evidence from RCTs, starting at high quality and downgrading for risk of bias, imprecision, inconsistency, indirectness and publication bias.

We rated the quality of the evidence for the following main outcomes:

  1. Disease-free survival at 5 years

  2. Overall survival at 5 years

  3. Local recurrences

  4. Lymph nodes retrieved

  5. CRM positivity

  6. 30-day morbidity

  7. Hospital stay (days)

Results

Description of studies

See: Characteristics of included studies, Characteristics of excluded studies and Characteristics of ongoing studies.

Results of the search

Our searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE identified 90, 253 and 852 results respectively. In addition we handsearched MEDLINE for any missed publications for the included trials. After exclusion of duplicates, we screened 953 references and identified 45 eligible references, as shown in the flow chart (Figure 1).

Figure 1.

Study selection flow diagram.

Included studies

From the 29 references, we identified two ongoing trials and 14 published clinical trials. Most larger trials have published their results at several stages in different papers. Both ongoing trials (ACTRN12609000663257 and NCT00726622) are still recruiting participants and no results have been published yet. Of the 14 published trials, two (Kang 2010; COLOR 2 a 2013) completed participant recruitment but have not yet published long-term data on survival. The COLOR 2 trial has a second published paper on a local subgroup, referred to as COLOR 2 b 2011 in this review. The Hong Kong trials are divided into the low rectal cancer group in Ng 2008 and the rectosigmoid group in Hong Kong a 2004, with the last subdivided in four papers because results are published for different subgroups as shown in the Characteristics of included studies. Hong Kong a 2004 is the biggest group, presenting upper rectum and sigmoid data, Hong Kong b 2009 is the upper rectal subgroup and reports 10-year follow-up data. Hong Kong c 2000 and Hong Kong d 2003 are both small subgroups of Hong Kong a 2004 and present only short-term data on immunological response.

The UK MRC CLASICC study is presented across nine papers, with six grouped as MRC CLASICC a 2005, giving respectively the short-term, three-year, five-year and 10-year results, the costs and an analysis of long term complications of the same participant group. MRC CLASICC c 2001 (one) and MRC CLASICC b 2005 (two) include papers for a selected or local participant subgroup and are therefore reported separately. King 2006 also consists of two papers, with the second paper focusing on functional recovery in the same participant group. The remaining eight clinical trials have one reference each, with the note that Zhou 2004 and Zhou 2007 are different trials and different authors despite the coincidence of names.

All 14 clinical trials were published as full papers and involved a total of 3528 rectal cancer patients (range 19 to 1044). The characteristics of these trials are described in 20 separate data sets and thus tables to allow for sufficient details on six additional subgroup papers.

All studies had quite similar exclusion criteria. The most common were: T4 rectal cancer, rectal cancer recurrence, people with synchronous or metachronous colorectal cancer, metastatic disease, emergency surgery, intestinal obstruction or perforation, contraindication for laparoscopy and no informed consent. The majority of the studies described the technique for laparoscopic total mesorectal excision (TME). Perioperative treatment of participants was not described in most of the trials. Six studies had a standardised protocol (Hong Kong a 2004; Braga 2007; Ng 2008; Kang 2010; COLOR 2 b 2011; Liang 2011) and only two had an enhanced recovery protocol (King 2006; Lujan 2009). Data on the type of anaesthesia and analgesia were not given in most studies.

Most studies reported on a range of different outcomes. The most commonly assessed were overall and disease-free survival rates, local recurrence rates, adequacy of oncological resection (margins and number of lymph nodes removed), duration of surgery, conversion rate, mortality, morbidity, anastomotic leakage, postoperative pain, gastrointestinal recovery rate and hospital stay. Most studies lacked a definition of conversion. The most common causes for conversion to open surgery were tumour invasion of adjacent structures or bulky tumours, dense adhesions and technical failure. Few studies evaluated quality of life (MRC CLASICC a 2005; MRC CLASICC b 2005; King 2006; Braga 2007; Kang 2010), immune response (Hong Kong c 2000; MRC CLASICC c 2001; Hong Kong d 2003; Zhou 2007; COLOR 2 b 2011) or costs (Hong Kong a 2004; MRC CLASICC a 2005; King 2006; Braga 2007; Ng 2008).

Excluded studies

Sixteen papers were excluded for the following reasons: two studies were not completely randomised (Leung 1999; Mirza 2008) and two other studies presented the same data as another included study (Braga 2002; Braga 2005). Two studies included participants with benign disease (Milsom 1998; Polle 2007) and two other studies excluded people treated with TME for low rectal cancer (Schwenk 1998; Liu 2009). Four studies included colorectal cancer patients, but did not report the number of rectal cancer patients or any separate outcomes for rectal cancer (Kim 1998; JCOG 0404 2005; LAPKON II 2009; LaFa 2011). One study presented low-quality data from a period with a steep learning curve (Pan 2007). Three more studies turned out not to be prospective RCTs, but were a comparison with the national registry (Morris 2011), an economic comparison between UK and USA trials (Stead 2000), and a single-arm phase II trial (Yamamoto 2008).

Risk of bias in included studies

The risk of bias is described in the Characteristics of included studies section, and a summary is shown in Figure 2. Of the included trials, only one had a low risk of bias on all items and three scored low on six out of seven domains. Five were of unclear or low quality, with a high or unclear risk in at least five out of seven domains.

Figure 2.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

The method of randomisation was unclear in four trials, and allocation concealment was not described in seven trials. Only seven trials presented an adequate inclusion and randomisation flow diagram, including a description of the loss to follow-up.

Blinding

Because of the nature of the interventions, blinding is not an option in these trials. Instead of blinding, we assessed whether operative technique and postoperative care were standardised, and how outcome data and pathological data were registered. We assessed standardisation in three studies as inadequate. Outcome registration was adequate in eight studies and unknown in all other studies.

Incomplete outcome data

We did not detect any attrition bias. Not all studies reported on loss to follow-up. Questionnaire response rates were reported for both groups when eligible.

Selective reporting

Comparing the described protocols and methods to the reported results of the different studies, we did not find evidence of any selective reporting, although some studies did not report exact data on non-significant results mentioned in the text sections. An overview of studies and outcomes in Table 1 shows that most studies report on the same outcomes. Five papers reported only one outcome in a subgroup analysis of another trial and one study reported only one outcome for the included participant group.

Table 1. Reported outcomes
Study IDnLong-term survival30-day mortality30-day morbidityLong-term morbidityLymphnodesGastrointestinal recoveryPainBleedingLength of hospital stayImmune responseQuality of lifeCost
Araujo 200328--+-+--++---
Braga 20071685y/3y+++++-++-++
COLOR 2 a 20131044-++-+++++---
COLOR 2 b 201140-++-+--+++--
Hong Kong a 20044035y++-+++++--+
Hong Kong b 200915310y--+-+------
Hong Kong c 200034---------+--
Hong Kong d 200340---------+--
Kang 2010340-++-+++++-+-
King 200619-++----++-++
Liang 20113433y++-++-+----
Liu 2010186-++-+--++---
Lujan 20092045y++-++-++---
MRC CLASICC a 200538110y/5y/3y++-++--+-+-
MRC CLASICC b 2005148----------+-
MRC CLASICC c 2001236---------+--
Ng 2008995y++-+++++--+
Pechlivanides 200773----+-------
Zhou 2004171-++--+-++---
Zhou 200771---------+--

Other potential sources of bias

An important source of bias is the experience of the surgeons conducting LTME, because of the known steep learning curve. (Schlachta 2001; Tekkis 2005) When only one experienced surgical team is involved, this bias can be limited, but it can be extensive in large multi centre trials or less experienced teams. Only the MRC CLASICC a 2005 and Kang 2010 defined the experience of their surgeons as based on at least 20 procedures. Four other studies only stated that their surgeons were "well experienced" or "the most experienced" (Hong Kong a 2004; Braga 2007; Pechlivanides 2007; Ng 2008;). The remaining eight did not describe surgeons' experience at all or stated only a single surgeon or team performed the procedures.

Effects of interventions

See: Summary of findings for the main comparison Laparoscopic versus open total mesorectal excision for rectal cancer

Disease-free and overall survival
The disease-free and overall survival rates have been reported in only six studies including 1494 participants, because of lack of follow-up in the other eight studies. Two of these are trials that will report on these results in the near future (Kang 2010; COLOR 2 b 2011), while the other six did not mention any long-term outcomes in their Methods or protocol.

The combined data for these studies do not show statistical significant differences in disease-free survival at three ((OR 1.08; 95% CI 0.67 to 1.74), five (OR 1.02; 95% CI 0.76 to 1.38) and 10 years ((OR 1.25; 95% CI 0.51 to 3.06) Analysis 1.1) for LTME and OTME. Regarding overall survival at three (OR 1.00; 95% CI 0.70 to 1.42), five (OR 1.15; 95% CI 0.87 to 1.52) or 10 years ((OR 1.15; 95% CI 0.80 to 1.65); Analysis 1.2), again no differences could be found between the groups. Braga 2007 could not be included in the meta-analysis because data were only shown in a Kaplan-Meier curve, but did not show any differences between LTME and OTME groups. See Figure 3.

Figure 3.

Forest plot of comparison: 2 Survival and recurrences, outcome: 2.1 Disease free survival.

Ng 2012 has reported the combined 10-year follow-up of Hong Kong a 2004 and Ng 2008 (n = 278) in a conference abstract, and reported no statistically significant differences in survival and recurrences (disease-free survival 82.5% versus 77.6%, P = 0.443, overall survival 63.0% versus 61.1%, P = 0.505 and locoregional recurrences 5.5% versus 9.3%, P = 0.296).

Recurrences
There are no statistical significant differences seen in recurrence rates between LTME and OTME (local OR 0.89; 95% CI 0.57 to 1.39; Analysis 1.3, and distant OR 0.96; 95% CI 0.70 to 1.32; Analysis 1.4). As for port site metastases, only 11 participants (0.9%) in the LTME group developed a port site metastasis (Analysis 1.5). Eight were an extraction site recurrence, leaving only one true port site metastasis. The other two recurrences were not specified. Only three studies described the use of a wound protector in LTME, and reported a similar total of two (0.8%) port site recurrences (Hong Kong a 2004; Zhou 2004; Kang 2010).

Quality of resection: CRM positivity and number of lymph nodes retrieved
One of the most important variables for measuring the quality of the oncological resection and predicting recurrence and survival are circumferential margin involvement and number of lymph nodes retrieved. Eleven RCTs describe the number of retrieved lymph nodes, with no difference between both groups (MD -0.43; 95% CI -1.13 to 0.26; Analysis 2.1). Eight studies reported on circumferential margin positivity, with no difference between LTME and OTME (OR 0.99; 95% CI 0.71 to 1.40; Analysis 2.2).

Duration of surgery, incision length and conversion rate
The duration of surgery was longer for LTME in 11 out of 12 included trials for this analysis, with a difference of 37 minutes (MD 37.48; 95% CI 27.80 to 47.15; Analysis 2.3). Two other studies did not report on surgical time. Four studies reporting on incision length all found a shorter incision length for LTME with a mean difference of 12 centimetres (MD -12.83; 95% CI -14.87 to -10.80; Analysis 2.4).

All studies except two (Zhou 2004; Zhou 2007) describe the conversion rate for the laparoscopic group (Analysis 2.5). The mean conversion rate was 14.5% (0% - 34%), and as described in MRC CLASICC a 2005, is highly dependent on the location of the tumour and the experience of the surgeon. For most studies, the surgeons' experience was not clearly stated and therefore cannot be compared from these results.

Intraoperative morbidity, blood loss and transfusion requirement
Ten studies described less intraoperative blood loss or transfusion requirement for LTME with a mean difference of 102 millilitres (MD -101.78; 95% CI -147.57 to -55.98; Analysis 2.6) and an odds ratio for transfusion requirement of 0.34 (95% CI 0.19 to 0.62; Analysis 2.7). Only King 2006 described a higher transfusion requirement for LTME, but a lower percentage of participants with over 100 millilitres of blood loss during surgery (27% versus 95%, P < 0.001). The overall intraoperative morbidity was described in four studies and was 11.3% for LTME versus 12.0% for OTME (OR 0.86; 95% CI 0.62 to 1.18; Analysis 2.8). There were insufficient data to compare bowel injury, haemorrhage and solid organ injury separately but individual studies did not show any differences.

Postoperative morbidity and mortality
The overall complication rate was 29.3% (LTME) and 27.5% (OTME) (OR 0.94; 95% CI 0.80 to 1.10; Analysis 3.1), with fewer wound infections and less postoperative bleeding in the LTME group (OR 0.68; 95% CI 0.50 to 0.93 (Analysis 3.2) and OR 0.30; 95% CI 0.10 to 0.93 (Analysis 3.3)). We found no differences in urinary bladder infection or retention (OR 1.23; 95% CI 0.83 to 1.81; Analysis 3.4) and pneumonia (OR 1.32; 95% CI 0.83 to 2.09; Analysis 3.5) between both groups. See Figure 4.

Figure 4.

Forest plot of comparison: 4 Short term morbidity and mortality, outcome: 4.1 30d morbidity (total).

Ten studies described similar anastomotic leakage rate for both groups (7.7% vs 6.3% OR 1.01; 95% CI 0.73 to 1.40; Analysis 3.6), while two other trials only included abdominoperineal resection and did not have anastomotic leakage as an outcome. Consequently, the need for reoperation was 5.1% and 5.8% (OR 0.82; 95% CI 0.57 to 1.20; Analysis 3.7) in the LTME and OTME groups respectively. The anastomotic leakage rate has been corrected for participants without an anastomosis.

Data on postoperative mortality were available for 11 studies, with similar mortality rates for the two treatment groups for individual and grouped data (OR 0.81; 95% CI 0.50 to 1.32; Analysis 3.8). Four of them (Zhou 2004; Kang 2010; Liu 2010; Liang 2011) reported no 30-day mortality in either group.

Postoperative pain
Postoperative pain can be assessed in many different ways. Common measures are a visual analogical scale (VAS) score, patient-controlled anaesthesia (PCA) use, days of morphine use and epidural insufficiency requiring opioid use. Six studies reported results for pain score and analgesic use, and all reported lower analgesic use in the LTME group (standardised mean difference (SMD) -0.60; 95% CI -0.93 to -0.27; Analysis 4.1). COLOR 2 a 2013 reported on the percentage of participants using epidural, opioids or other analgesics, with less epidural use in the LTME group.Three trials reported on VAS pain scores, with a lower pain score for LTME at day one (MD -0.74; 95% CI -1.04 to -0.44; Analysis 4.2).

Gastrointestinal recovery and hospital stay
Length of hospital stay was given in 11 studies, and showed a reduction of two days for the LTME group (MD -2.16; 95% CI -3.22 to -1.10; Analysis 4.3). This is reflected in the gastrointestinal recovery rate to a faster resumption of a normal diet (MD -0.52; 95% CI -0.80 to -0.23; Analysis 4.4), and an earlier first bowel movement (MD -0.86; 95% CI -1.17 to -0.54; Analysis 4.5) in the LTME group. See Figure 5.

Figure 5.

Forest plot of comparison: 5 Post op recovery, outcome: 5.3 Hospital stay.

Long-term morbidity: Incisional herniae and bowel obstruction
Only three studies reported on long-term morbidity from incisional hernia and intestinal obstruction (MRC CLASICC a 2005; Braga 2007; Hong Kong b 2009). No statistically significant difference between OTME and LTME was seen (OR 0.84; 95% CI 0.32 to 2.21; Analysis 5.1). Intestinal obstruction occurred less frequently in the LTME group (OR 0.30; 95% CI 0.12 to 0.75; Analysis 5.2).

Quality of life: physical and sexual functioning
Four studies reported on quality of life using questionnaires (MRC CLASICC a 2005; King 2006; Braga 2007; Kang 2010). Only two reported on bladder and sexual functioning (MRC CLASICC a 2005; Kang 2010).

Of the four reporting on physical functioning, three reported significantly better functioning in the LTME group at three, six or 12 months. The MRC CLASICC a 2005 showed return to normal functioning at three months for both groups.

The reports on bladder and sexual functioning suffered from low response rates, varying from 71% overall response rate down to 10% on specific questions about sexual enjoyment and problems. Kang 2010 showed a baseline difference in sexual problems, but better sexual functioning after three months in both groups. In contrast, male sexual problems were worse three months after surgery but there was no difference between both groups. The LTME group had significantly fewer micturition, gastrointestinal and defecation problems at three months after surgery.

MRC CLASICC a 2005 and MRC CLASICC b 2005 both reported on participants in the CLASICC trial, but used different populations, questionnaires and time points. MRC CLASICC b 2005 showed worse sexual functioning after LTME, specifically for erectile dysfunction, but none were statistically significant. No differences in sexual interest, activity and enjoyment were seen at any time point, although for women there was a significant decrease compared to the preoperative baseline for both groups.

Immune response
Five studies described some short-term differences in immune response (MRC CLASICC c 2001; Hong Kong d 2003; Zhou 2007; Hong Kong c 2000; COLOR 2 b 2011). They all reported different parameters, including C-reactive protein (CRP), white blood cell count (WBC) and Interleukin-6 (IL-6). Two studies reported on B-cell, T-cell, cortisol and natural-killer cell (NK-cell) levels.

MRC CLASICC c 2001 had the largest population (n = 161), but did not show any differences in T-cell, B-cell and NK-cell levels at day three. Zhou 2007 included 71 participants and the three other studies around 40 participants each. Hong Kong c 2000 showed higher levels of IL-6 and CRP, with a peak for IL-6 at two hours (P < 0.001) and CRP at 48 hours (P < 0.01) in the OTME group. The same results were shown by Zhou 2007, but they were measured at one and three days with a difference for IL-6 at day one and for CRP at day one and three for the OTME group. Cortisol levels and WBC were also higher in the OTME group at day one. COLOR 2 b 2011 expressed results only as ratios compared to preoperative values and showed less increase in IL-6 level at two hours postoperatively in the LTME group. Cortisol, WBC and CRP did not show any differences at 2, 24 and 72 hours. Finally, Hong Kong d 2003 did not show any differences at days one and three for WBC, NK-cell, T-cell and B-cell levels, but for T-cell and B-cell levels there was less suppression in the LTME group at day eight.

Costs
An analysis of costs was included in five studies (Hong Kong a 2004; MRC CLASICC a 2005; King 2006; Braga 2007; Ng 2008). Data were too heterogeneous to be included in a meta-analysis. Braga 2007 only reported the difference in costs in which the benefits of LTME could not compensate for the additional operating room charges, with a mean difference of USD 351 more for LTME. The four other studies calculated the costs per participant randomised. King 2006 and MRC CLASICC a 2005 reported the median direct and indirect costs for LTME. King 2006 reported the costs at GBP 6344 for LTME and GBP 6786 for OTME resulting in a saving of GBP 353 for LTME while being the only study in this analysis that used a fast-track programme. MRC CLASICC a 2005 reported the opposite, with GBP 8259 for LTME and GBP 7820 for OTME, resulting in GBP 439 higher costs for LTME. Neither result achieved a statistically significant difference. Hong Kong a 2004 and Ng 2008 reported only the direct costs, with means of USD 9297 and USD 9588 for LTME and USD 7148 and USD 7517 for OTME with a significant difference of about USD 2000 in favour of OTME.

Discussion

Summary of main results

Nine studies (n = 1877) reported on at least one of the long-term survival or recurrence outcomes and the meta-analyses as well as the separate studies showed similar long-term survival and recurrence rates for laparoscopic and open total mesorectal excision.

We found a mean difference in hospital stay of two days, with individual studies reporting a 0.5- to 5-day difference in favour of LTME. Schwenk 2005 found comparable results for colon cancer with a mean difference of 1.5 days in favour of the laparoscopic group. Seven studies standardised their postoperative protocol, but only two implemented an enhanced recovery programme.

Overall completeness and applicability of evidence

Benefits of laparoscopic surgery are attributable to causing less surgical trauma to the patient, which has a positive effect on surgery-induced immunosuppression. This can be demonstrated by taking measurements after surgery, with different peak moments for several parameters. The included studies in this review did not take measurements at the same time point, which may explain why not all of them could show differences in similar parameters. Reduced immunosuppression could be related to a lower complication rate and to shorter hospital stay, and may reduce development of postoperative metastasis (although this has yet to be shown in a randomised trial (Hogan 2011)).

The included RCTs include studies and subgroups of patients with low, mid and high rectal cancer and both APR and anterior resections with and without anastomosis. These differences can affect outcomes, especially the various techniques for low rectal resections can influence the circumferential margins and therefore local recurrences and survival. Lack of reporting of the CRM is an important issue with only eight out of fourteen studies describing this outcome. The number of retrieved lymph nodes is described by eleven studies but is more dependent on difference in high and low vascular ligations of the mesentery than on open or laparoscopic surgery. (Kessler 2013)

With a mean age between 44 and 72, three studies including T4 carcinoma and six offering neoadjuvant treatment in selected cases and a tumour localisation between 15 cm and the anal verge, there is a fair amount of heterogeneity among the included studies. Especially the early and smaller studies included a younger and healthier study population compared to the average rectal cancer patient. Of the four ongoing trials (n = 470 to 1100 participants), three (Kang 2010; ACTRN12609000663257; NCT00726622) require neoadjuvant treatment for selected stages of rectal cancer and the fourth (COLOR 2 a 2013) stratifies the randomisation for neoadjuvant treatment. This might influence both long term and short term outcomes as only six offered neoadjuvant therapy in this review. All ongoing studies include abdominoperineal resections as well as (low) anterior resections, but the maximum distance from the anal verge varies between 9 cm (Kang 2010), 12 cm (NCT00726622) and 15 cm (ACTRN12609000663257; COLOR 2 a 2013).

Another important difference between the included RCTs and current practise are the fast track recovery programmes such as the enhanced recovery after surgery (ERAS) programme. Only two included studies describe an enhanced recovery programme (King 2006; Lujan 2009). COLOR 2 a 2013 referred to local protocols, whereas the other two ongoing studies do not describe their postoperative protocol in the online summary. The LAFA trial (Vlug 2011) showed laparoscopic surgery in combination with fast track recovery resulted in the fastest recovery and hospital discharge compared to regular care and open surgery.

Quality of the evidence

Since 1998, 14 RCTs have been published to answer the question whether LTME results in better short-term results and at least equal long-term oncological results. The quality of these studies varied extensively, as did the number of included participants. Although the total mesorectal excision principle has been established since 1986, treatment protocols have changed. Surgeons gained more experience in laparoscopic colon and rectal cancer surgery, fast-track protocols were introduced and neoadjuvant treatment became a standard of care in a proportion of cases. All of these factors are able to influence the long-term results of these trials; however they should influence both the laparoscopic and open groups equally, except for the learning curve for laparoscopic procedures.

The quality of the evidence for the most important outcomes was moderate (Summary of findings for the main comparison). This means that further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. The main reason is the imprecision of the confidence intervals, they allow for a variability in odds ratios up to 40% on both sides, which contributes to an absolute increase or decrease of 6% in disease free survival, 5% in overall survival, 2% in local recurrences, and 3% in 30-day morbidity. The COLOR 2 a 2013 trial used a 5% margin for local recurrences for their non-inferiority design, therefore our results remain within those limits.

Potential biases in the review process

Publication bias is a threat for any systematic review. We believe we have missed no important randomised controlled trials after screening reference lists of included trials and other relevant studies and reviews, in addition to the extensive systematic searching of electronic databases and trials registers. We have described all registered ongoing trials.

In the current literature regarding learning curves in laparoscopic colorectal surgery, a wide range of numbers of procedures is reported until a flat curve is achieve, ranging from 11 to 15 colectomies (Simons 1995), 30 colorectal resections (Schlachta 2001) and 60 to 65 colectomies (Tekkis 2005). For the open total mesorectal excision (OTME) technique, the cut-off point for percentage of clear resection margins is defined as around 50 procedures (Oh 2011). This suggests that only the surgeons in Kang 2010 are assumed to have had sufficient experience for a good laparoscopic resection and results may further improve over time.

Agreements and disagreements with other studies or reviews

A meta-analysis of RCTs on laparoscopic and open colorectal surgery (Sammour 2011) has shown a higher intraoperative complication rate for laparoscopic surgery of 6.3% versus 3.9% for open surgery (OR)1.55, 95%CI 1.12 to 2.15). The rate of bowel perforations was 2.1% versus 0.9% (OR 2.28, 95% CI 1.27 to 4.10) across 3018 participants. These differences had limited effect on the outcome, with an average postoperative complication rate of 28%. Compared to the intraoperative complication rate of 11.3% in LTME versus 12.0% in OTME in four included studies in our review (n = 1618), we cannot confirm these previously reported complication rates for LTME.

The results of this review confirm what other colorectal and rectal trials have suggested: short-term results are similar with faster recovery in the LTME group and no statistically significant differences were found in the long-term oncological results. For rectal cancer, non-randomised trials have suggested oncological safe resections as presented in the previous version of this review (Fleshman 1999; Feliciotti 2003; Breukink 2006). Since then, several other reviews have been published describing the same results. Aziz 2006, Gao 2006, Anderson 2008 and Poon 2009 included mainly non-randomised trials, and Row 2010 was a literature review. Ohtani 2011, Huang 2011 and Trastulli 2012 were the first to include only randomised trials. However, Ohtani 2011 also included three non-randomised trials, Huang 2011 included only six trials and Trastulli 2012 nine trials, whereas this systematic review was able to identify 14. In addition, the Cochrane review of laparoscopic colorectal cancer (Kuhry 2008) presented separate meta-analyses for four included rectal cancer RCTs.

Authors' conclusions

Implications for practice

There is currently moderate quality evidence that laparoscopic total mesorectal excision (TME) has similar effects to open TME on long term survival outcomes for the treatment of rectal cancer. The quality of the evidence was downgraded due to imprecision and we cannot rule out either approach being superior. There is moderate quality evidence that it leads to better short-term post-surgical outcomes in terms of recovery for non-locally advanced rectal cancer and shorter hospital stay. Currently results are consistent in showing a similar disease-free survival and overall survival, and for recurrences after at least three years and up to 10 years although due to imprecision we cannot rule out superiority of either approach. We await long-term data from a number of ongoing and recently completed studies to contribute to a more robust analysis of long-term disease free, overall survival and local recurrence.

Implications for research

The evidence presented in this systematic review is sufficient to establish the overall and long-term oncological safety of laparoscopic TME. However, at this moment the available data are still insufficient to confirm these results for subgroups such as abdominoperineal resections, following neoadjuvant therapy, in locally advanced disease and in combination with fast track recovery protocols.

Acknowledgements

The authors would like to thank Ms Marija Barbateskovic, the Trial Search Co-ordinator of the Cochrane Colorectal Cancer Group for her support with the search strategies and performing the searches for this update.

Data and analyses

Download statistical data

Comparison 1. Survival and recurrences
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Disease-free survival5 Odds Ratio (M-H, Fixed, 95% CI)Subtotals only
1.1 10-year1130Odds Ratio (M-H, Fixed, 95% CI)1.25 [0.51, 3.06]
1.2 5-year4943Odds Ratio (M-H, Fixed, 95% CI)1.02 [0.76, 1.38]
1.3 3-year1326Odds Ratio (M-H, Fixed, 95% CI)1.08 [0.67, 1.74]
2 Overall survival6 Odds Ratio (M-H, Fixed, 95% CI)Subtotals only
2.1 10-year2534Odds Ratio (M-H, Fixed, 95% CI)1.15 [0.80, 1.65]
2.2 5-year4987Odds Ratio (M-H, Fixed, 95% CI)1.15 [0.87, 1.52]
2.3 3-year2682Odds Ratio (M-H, Fixed, 95% CI)1.00 [0.70, 1.42]
3 Local recurrences81538Odds Ratio (M-H, Fixed, 95% CI)0.89 [0.57, 1.39]
3.1 5-year5963Odds Ratio (M-H, Fixed, 95% CI)0.94 [0.49, 1.81]
3.2 3-year3575Odds Ratio (M-H, Fixed, 95% CI)0.84 [0.46, 1.56]
4 Distant recurrences61341Odds Ratio (M-H, Fixed, 95% CI)0.96 [0.70, 1.32]
5 Wound/port site metastases72130Odds Ratio (M-H, Fixed, 95% CI)2.76 [0.75, 10.20]
Analysis 1.1.

Comparison 1 Survival and recurrences, Outcome 1 Disease-free survival.

Analysis 1.2.

Comparison 1 Survival and recurrences, Outcome 2 Overall survival.

Analysis 1.3.

Comparison 1 Survival and recurrences, Outcome 3 Local recurrences.

Analysis 1.4.

Comparison 1 Survival and recurrences, Outcome 4 Distant recurrences.

Analysis 1.5.

Comparison 1 Survival and recurrences, Outcome 5 Wound/port site metastases.

Comparison 2. Surgical data
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Lymph nodes retrieved113682Mean Difference (IV, Random, 95% CI)-0.43 [-1.13, 0.26]
2 CRM positivity82313Odds Ratio (M-H, Fixed, 95% CI)0.99 [0.71, 1.40]
3 Duration of surgery123840Mean Difference (IV, Random, 95% CI)37.48 [27.80, 47.15]
4 Incision length41488Mean Difference (IV, Random, 95% CI)-12.83 [-14.87, -10.80]
5 Conversion rate  Other dataNo numeric data
6 Blood loss82615Mean Difference (IV, Random, 95% CI)-101.78 [-147.57, -55.98]
7 Transfusion requirement5939Odds Ratio (M-H, Fixed, 95% CI)0.34 [0.19, 0.62]
8 Intraoperative morbidity41618Odds Ratio (M-H, Fixed, 95% CI)0.86 [0.62, 1.18]
Analysis 2.1.

Comparison 2 Surgical data, Outcome 1 Lymph nodes retrieved.

Analysis 2.2.

Comparison 2 Surgical data, Outcome 2 CRM positivity.

Analysis 2.3.

Comparison 2 Surgical data, Outcome 3 Duration of surgery.

Analysis 2.4.

Comparison 2 Surgical data, Outcome 4 Incision length.

Analysis 2.5.

Comparison 2 Surgical data, Outcome 5 Conversion rate.

Conversion rate
Study 
Araujo 20030 (0/13)
Braga 20077.2 (6/83)
COLOR 2 a 201317 (121/695)
Hong Kong a 200423.2 (47/203)
Kang 20101.2 (2/170)
King 20067.3 (3/41)
Liang 20110.5 (1/169)
Liu 20100 (0/98)
Lujan 20097.9 (8/101)
MRC CLASICC a 200533.9 (82/242)
Ng 20089.8 (5/51)
Pechlivanides 20072.9 (1/34)
Zhou 2004Unknown
Zhou 2007Unknown
Analysis 2.6.

Comparison 2 Surgical data, Outcome 6 Blood loss.

Analysis 2.7.

Comparison 2 Surgical data, Outcome 7 Transfusion requirement.

Analysis 2.8.

Comparison 2 Surgical data, Outcome 8 Intraoperative morbidity.

Comparison 3. Short-term morbidity and mortality
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 30-day morbidity (total)113397Odds Ratio (M-H, Fixed, 95% CI)0.94 [0.80, 1.10]
2 Wound infection103337Odds Ratio (M-H, Fixed, 95% CI)0.68 [0.50, 0.93]
3 Bleeding51181Odds Ratio (M-H, Fixed, 95% CI)0.30 [0.10, 0.93]
4 Urinary complications81756Odds Ratio (M-H, Fixed, 95% CI)1.23 [0.83, 1.81]
5 Pneumonia82668Odds Ratio (M-H, Fixed, 95% CI)1.32 [0.83, 2.09]
6 Anastomotic leakage102505Odds Ratio (M-H, Fixed, 95% CI)1.01 [0.73, 1.40]
7 Need for reoperation72316Odds Ratio (M-H, Fixed, 95% CI)0.82 [0.57, 1.20]
8 30-day mortality113812Odds Ratio (M-H, Fixed, 95% CI)0.81 [0.50, 1.32]
Analysis 3.1.

Comparison 3 Short-term morbidity and mortality, Outcome 1 30-day morbidity (total).

Analysis 3.2.

Comparison 3 Short-term morbidity and mortality, Outcome 2 Wound infection.

Analysis 3.3.

Comparison 3 Short-term morbidity and mortality, Outcome 3 Bleeding.

Analysis 3.4.

Comparison 3 Short-term morbidity and mortality, Outcome 4 Urinary complications.

Analysis 3.5.

Comparison 3 Short-term morbidity and mortality, Outcome 5 Pneumonia.

Analysis 3.6.

Comparison 3 Short-term morbidity and mortality, Outcome 6 Anastomotic leakage.

Analysis 3.7.

Comparison 3 Short-term morbidity and mortality, Outcome 7 Need for reoperation.

Analysis 3.8.

Comparison 3 Short-term morbidity and mortality, Outcome 8 30-day mortality.

Comparison 4. Postoperative recovery
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Analgesia use (number of doses)51199Std. Mean Difference (IV, Random, 95% CI)-0.60 [-0.93, -0.27]
2 Day 1 pain score (VAS)3776Mean Difference (IV, Fixed, 95% CI)-0.74 [-1.04, -0.44]
3 Hospital stay (days)113084Mean Difference (IV, Random, 95% CI)-2.16 [-3.22, -1.10]
4 Time to normal diet (days)82109Mean Difference (IV, Random, 95% CI)-0.52 [-0.80, -0.23]
5 Time to first defecation (days)82893Mean Difference (IV, Random, 95% CI)-0.86 [-1.17, -0.54]
Analysis 4.1.

Comparison 4 Postoperative recovery, Outcome 1 Analgesia use (number of doses).

Analysis 4.2.

Comparison 4 Postoperative recovery, Outcome 2 Day 1 pain score (VAS).

Analysis 4.3.

Comparison 4 Postoperative recovery, Outcome 3 Hospital stay (days).

Analysis 4.4.

Comparison 4 Postoperative recovery, Outcome 4 Time to normal diet (days).

Analysis 4.5.

Comparison 4 Postoperative recovery, Outcome 5 Time to first defecation (days).

Comparison 5. Long term morbidity
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Incisional hernia3508Odds Ratio (M-H, Random, 95% CI)0.84 [0.32, 2.21]
2 Intestinal obstruction3508Odds Ratio (M-H, Fixed, 95% CI)0.30 [0.12, 0.75]
Analysis 5.1.

Comparison 5 Long term morbidity, Outcome 1 Incisional hernia.

Analysis 5.2.

Comparison 5 Long term morbidity, Outcome 2 Intestinal obstruction.

Appendices

Appendix 1. Cochrane Library (CENTRAL) search strategy

#Search
1MeSH descriptor: [Laparoscopy] explode all trees
2MeSH descriptor: [Surgical Procedures, Minimally Invasive] explode all trees
3laparoscopy OR laparoscop* OR minimally invasive surgery
4(#1 or #2 or #3)
5(anterior resecti*) OR (abdominoperineal resecti*) OR (total mesorectal excisi*)
6((sexual* or gastrointestinal or urogenital or bladder) near/3 functi*):ti,ab,kw
7(quality of life or QoL or survival or recurrence):ti,ab,kw
8MeSH descriptor: [Erectile Dysfunction] explode all trees
9MeSH descriptor: [Urinary Bladder] explode all trees
10MeSH descriptor: [Quality of Life] explode all trees
11MeSH descriptor: [Survival] explode all trees
12MeSH descriptor: [Recurrence] explode all trees
13(#5 or #6 or #7 or #8 or #9 or #10 or #11 or #12)
14MeSH descriptor: [Rectal Neoplasms] explode all trees
15((rect* or anal* or anus*) near/3 (carcinom* or neoplas* or adenocarcinom* or cancer* or tumor* or tumour* or sarcom*)):ti,ab,kw
16(#14 or #15)
17(#4 and #13 and #16)

Appendix 2. MEDLINE (Ovid) search strategy

#Search
1exp Laparoscopy/
2exp Surgical Procedures, Minimally Invasive/
3(laparoscop* or minimally invasive surgery).mp.
41 or 2 or 3
5(anterior resecti* or abdominoperineal resecti* or total mesorectal excisi*).mp.
6((sexual* or gastrointestinal or urogenital or bladder) adj3 functi*).mp.
7(quality of life or QoL or survival or recurrence).mp.
8exp sexual dysfunction, physiological/ or exp urinary bladder/ or exp quality of life/ or exp survival/ or exp recurrence/
95 or 6 or 7 or 8
10exp Rectal Neoplasms/
11((rect* or anal* or anus*) adj3 (carcinom* or neoplas* or adenocarcinom* or cancer* or tumor* or tumour* or sarcom*)).mp.
1210 or 11
134 and 9 and 12
14randomized controlled trial.pt.
15controlled clinical trial.pt.
16randomized.ab.
17placebo.ab.
18clinical trial.sh.
19randomly.ab.
20trial.ti.
2114 or 15 or 16 or 17 or 18 or 19 or 20
22humans.sh.
2321 and 22
2413 and 23
25limit 24 to yr="1990 -Current"

Appendix 3. EMBASE (Ovid) search strategy

#Search
1exp LAPAROSCOPY/
2exp minimally invasive surgery/
3(laparoscop* or minimally invasive surgery).mp.
41 or 2 or 3
5exp rectum anterior resection/ or exp rectum abdominoperineal resection/ or exp sexual function/ or exp bladder/ or exp quality of life/ or exp survival/ or exp recurrent disease/
6(anterior resecti* or abdominoperineal resecti* or total mesorectal excisi* or quality of life or QoL or survival or recurrence).mp.
7((sexual* or gastrointestinal or urogenital or bladder) adj3 functi*).mp.
85 or 6 or 7
9exp rectum tumor/
10((rect* or anal* or anus*) adj3 (carcinom* or neoplas* or adenocarcinom* or cancer* or tumor* or tumour* or sarcom*)).mp.
119 or 10
124 and 8 and 11
13randomized controlled trial/
14randomization/
15controlled study/
16multicenter study/
17phase 3 clinical trial/
18phase 4 clinical trial/
19double blind procedure/
20single blind procedure/
21((singl* or doubl* or trebl* or tripl*) adj (blind* or mask*)).ti,ab.
22(random* or cross* over* or factorial* or placebo* or volunteer*).ti,ab.
2318 or 15 or 19 or 21 or 14 or 20 or 16 or 13 or 22 or 17
24"human*".ti,ab.
25(animal* or nonhuman*).ti,ab.
2625 and 24
2725 not 26
2823 not 27
2912 and 28
30limit 29 to yr="1990 -Current"

What's new

DateEventDescription
2 February 2013New citation required and conclusions have changedNew search, analysis and conclusion
2 February 2013New search has been performedIn this updated review we included 14 trials (20 comparisons) ; 46 previously included studies from the first published version in 2006 were discarded and 12 new RCTs added.

History

Protocol first published: Issue 2, 2005
Review first published: Issue 4, 2006

DateEventDescription
5 August 2008AmendedConverted to new review format.
10 August 2006New citation required and conclusions have changedSubstantive amendment

Contributions of authors

Sandra Vennix, MD: First reviewer to search literature, assess quality of trials and collect data, manage the data and write the review.
Loeki Pelzers, MD: Second reviewer to search literature, assess quality of trials and collect data.
Nicole Bouvy, MD, PhD: Providing general advice on the review, help write the review.
Geerard Beets, MD, PhD: Providing general advice on the review, help write the review.
Jean-Pierre Pierie, MD, PhD: Performing previous work that was the foundation of the current review, providing general advice on the review.
Theo Wiggers, MD, PhD: Performing previous work that was the foundation of the current review, providing general advice on the review.
Stephanie Breukink, MD, PhD: Writing the protocol, performing previous work that was the foundation of the current review, providing general advice on the review, co-ordinating the review.

Declarations of interest

No funding/conflicts of interest declared by all authors.

Differences between protocol and review

Since the published protocol and original review, in this version we only include randomised controlled trials (RCTs) which compared laparoscopic with open total mesorectal excision. This has resulted in discarding the 46 non-randomised studies of the 48 included studies in favour of 12 new RCTs not originally included.In addition to the outcome measures given in the protocol, we have included long-term morbidity, recurrences and overall survival. We have excluded the respiratory recovery rate, as the definition is unclear and only one trial reported on this outcome.
For methodological assessment, we have discarded the scale by Sackett 2000, because we now only include randomised controlled trials. We now assess the included trials according to the CONSORT Statement 2010 and using the Cochrane 'Risk of bias' tool.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Araujo 2003

Methods

Single-centre RCT

Sao Paulo, Brazil
Number of patients assessed for eligibility but not randomised: unknown

Inclusion period: September 1997 to September 2000

Participantsn = 28 (LTME n = 13; OTME n= 15)
Inclusion criteria: primary rectal cancer suitable for APR, incomplete response after chemoradiation
Exclusion criteria: metastases
Age (y): 59.1 vs 56.4 (mean)
Dukes stage (%): A 39 vs 43; B 38 vs 21; C 23 vs 36; D 0 vs 0
Tumour location: distal rectum
Follow-up: 47.2 months (mean)
InterventionsLaparoscopic vs open TME
APR (%): 100
AR (%): 0
Colon (%): 0
Neoadjuvant therapy: all chemoradiation
OutcomesNo primary outcome stated
Length of follow-up, local and distant recurrences
Duration of surgery, need for transfusion, postoperative hospital stay, postoperative complications, need for reoperation, number of lymph nodes
NotesFunding or conflicts of interest: No statement
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk"were randomised to undergo treatment"
Allocation concealment (selection bias)Unclear riskUnknown, moment of randomisation unknown
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskLoss to follow-up not described, intention-to-treat not described
Selective reporting (reporting bias)High risk

No primary outcome stated, not all data given as described in Methods section

No sample size calculation

Other biasHigh risk

Published in a non-peer-reviewed journal,

Low diversity with distal rectal cancer only

Surgeon's experience unknown

Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk

Surgical procedure described according to TME

Postoperative protocol unknown

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described

Braga 2007

Methods

Single-centre RCT

Milan, Italy
Number of patients assessed for eligibility but not randomised: 28

Inclusion period: unknown

Participantsn = 168 (LTME n = 83; OTME n = 85)
Inclusion criteria: age > 18, histologically confirmed rectal cancer, suitable for elective surgery
Exclusion criteria: clinical infiltrative cancer, cardiovascular dysfunction, respiratory dysfunction, hepatic dysfunction, ongoing infection, plasma neutrophil level < 2 x10^9
Age (y): 62.8 vs 65.3 (mean)
Dukes stage (%): A 30 vs 28; B 19 vs 22; C 38 vs 34; D 13 vs 15
Tumour location: rectum < 15 cm
Follow-up: 53.6 months (mean)
InterventionsLaparoscopic vs open TME
APR (%): 8 vs 13
AR (%): 92 vs 87
Colon (%): 0
Neoadjuvant therapy: chemoradiation (T3 only)
OutcomesPrimary outcome: Short-term postoperative morbidity
Cost benefit analysis, quality of life, oncological outcome
Notes

Enlarged subgroup from Braga 2002

Funding or conflicts of interest: No statement

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer generated list, sealed envelopes
Allocation concealment (selection bias)Low riskOpened before induction of anaesthesia
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo loss to follow-up, intention-to-treat analysis
Selective reporting (reporting bias)Low risk

Survival given per stage, not combined and only in Kaplan-Meier curve

Sample size calculation performed

Other biasLow riskSame surgical team, "well experienced"
Blinding of participants and personnel (performance bias)
All outcomes
Low riskSurgical procedure according to TME
Standardised postoperative protocol and discharge
criteria, no enhanced recovery
Blinding of outcome assessment (detection bias)
All outcomes
Low riskComplications registered by independent team,
weekly clinic visits until 30 days

COLOR 2 a 2013

Methods

Multicentre RCT (30 academic centres)

Belgium, Canada, Denmark, Germany, The Netherlands, Spain, South Korea, Sweden
Number of patients assessed for eligibility but not randomised unknown

Inclusion period: January 2004 to May 2010

Participantsn = 1044 (LTME n = 699; OTME n = 345)
Inclusion criteria: Solitary rectal cancer at colonoscopy or barium enema x-ray, distal border within < 15 cm of anal verge, suitable for elective surgery, informed consent
Exclusion criteria: Metastatic disease, local resection, T4 tumours, T3 tumours with margins < 2 mm to endopelvic fascia on CT or MRI, other malignancy than adenocarcinoma, participant < 18 y, acute intestinal obstruction, > 1 colorectal tumour, FAP, HNPCC, Crohn's disease or ulcerative colitis, ASA > III, pregnancy
Age (y): 66.8 vs 65.8 (mean)
Gender (male): 64% vs 61%
Dukes stage (%): A 30 vs 29; B 31 vs 33; C 38 vs 38
Tumour location: rectum <15cm
Follow-up: short term data, 28 days
Interventions

Laparoscopic vs open TME
APR (%): 29 vs 23

LAR (%): 70 vs 77

Colon (%): 0

Neoadjuvant therapy: radiotherapy 59% vs 58%, chemotherapy 32% vs 34%

Outcomes

Primary outcome: local recurrences at 3 years (will be published later)

Secondary outcomes: Operating time, conversion rate, blood loss, postoperative recovery of gastrointestinal function, postoperative pain medication, length of hospital stay, morbidity and mortality within 28 days after surgery, histopathological outcomes and anastomotic leakage.

Notes

COLOR 2 b 2011 presents a local subgroup of 40 participants focusing on inflammatory response markers

Funding or conflicts of interest: Funding by Ethicon Endo-Surgery Europe, Swedish Cancer Foundation, West Gothia Region and Sahlgrenska University Hospital. The authors declare to have no conflicts of interest

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskParticipants randomised via online register with randomisation list stratified for centre, tumour location and preoperative radiotherapy
Allocation concealment (selection bias)Low riskCentral randomisation after registration in database
Incomplete outcome data (attrition bias)
All outcomes
Low riskIntention-to-treat analysis
Selective reporting (reporting bias)Low riskSample size calculation performed
Other biasLow riskSurgeon's technique and resection quality assessed prior to enrolment
Blinding of participants and personnel (performance bias)
All outcomes
Low riskLocal standardised postoperative protocols
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskObjective measurements

COLOR 2 b 2011

Methods

Single-centre RCT (University Hospital)

Amsterdam, The Netherlands
Number of patients assessed for eligibility but not randomised unknown

Inclusion period: June 2006 to December 2008

Participantsn = 40 (LTME n = 22; OTME n = 18)
Inclusion criteria: Solitary rectal cancer at colonoscopy or barium enema x-ray, distal border within < 15 cm of anal verge, suitable for elective surgery, informed consent
Exclusion criteria: Metastatic disease, local resection, T4 tumours, T3 tumours with margins < 2 mm to endopelvic fascia on CT or MRI, other malignancy than adenocarcinoma, patient < 18 y, acute intestinal obstruction, > 1 colorectal tumour, FAP, HNPCC, Crohn's disease or ulcerative colitis, ASA > III, pregnancy
Age (y): 64 vs 67 (median)
Gender (male): 73% vs 67%
Dukes stage (%): A 50 vs 27.8; B 22.3 vs 38.9; C 22.3 vs 22.2
Tumour location: rectum < 15 cm
Follow-up: 72 h
InterventionsLaparoscopic vs open TME
APR (%): 18 vs 28
LAR (%): 82 vs 72
Colon (%):0
Neoadjuvant therapy: unknown
OutcomesPrimary outcomes :Postoperative inflammatory response (IL-6, IL-8, CRP), immune status (WBC, HLA-DR), stress response (cortisol, prolactin, growth hormone)
Secondary outcomes: Hospital stay, complication rate, lymph nodes resected
Notes

Local subgroup of COLOR 2 a 2013

Funding or conflicts of interest: No statement

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskParticipants randomised within COLOR II trial, computer-generated list, stratified for preoperative radiotherapy and location of tumour
Allocation concealment (selection bias)Low riskRandomisation after entry of participant details in database
Incomplete outcome data (attrition bias)
All outcomes
Low riskIntention-to-treat analysis
Selective reporting (reporting bias)Unclear riskNo sample size calculation for this sub study
Other biasHigh riskSurgeon's experience: unknown
Blinding of participants and personnel (performance bias)
All outcomes
Low riskStandardised postoperative protocol per hospital
Blinding of outcome assessment (detection bias)
All outcomes
Low riskObjective measurements

Hong Kong a 2004

Methods

Two-centre RCT

Hong Kong, China
Number of patients assessed for eligibility but not randomised: 422

Inclusion period: September 1993 to October 2002

Participantsn = 403 (LTME n = 203; OTME n = 200)
Inclusion criteria: sigmoid and upper rectal cancer
Exclusion criteria: distance from anal verge < 5 cm, tumour size > 6 cm, T4 rectal cancer, previous abdominal operations in lower pelvis, intestinal obstruction or perforation, metastatic disease, no informed consent
Age (y): 67.1 vs 66.5 (mean)
Dukes stage (%): A 15 vs 14; B 35 vs 37; C 32 vs 35; D 18 vs 14
Tumour location: sigmoid and rectum >5 cm
Follow-up: 52.7 vs 49.2 months (median, participants alive)
InterventionsLaparoscopic vs open
APR (%): 0
LAR (%): 100
Colon (%):0
(Neo)adjuvant therapy: 8.4 vs 13.5 adjuvant radiotherapy, 18.7 vs 25.0 adjuvant chemotherapy
OutcomesPrimary outcome: 5-year disease-free survival,
Secondary outcomes: operation time, disposable instruments used, blood loss, transfusion requirement, analgesic requirement, visual analogue scale, time to flatus, time to opening bowel, time to normal diet, duration of hospital stay, 30-day mortality, morbidity
Notes

Short-term data rectosigmoid subgroup

Funding or conflicts of interest: The authors declare no conflicts of interest

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated sequence
Allocation concealment (selection bias)Low riskKept concealed by an independent operating theatre co-ordinator
Incomplete outcome data (attrition bias)
All outcomes
Low riskLoss to follow-up described, intention-to-treat analysis
Selective reporting (reporting bias)High risk

Sample size calculation performed

Ratio between sigmoid and rectal cancer not given

Other biasHigh risk

High diversity rectosigmoid carcinoma, ratio not given

Surgeon's experience: "Skilled in both laparoscopic and open colorectal surgery"

Blinding of participants and personnel (performance bias)
All outcomes
Low risk

Surgical procedure described

Standardised postoperative protocol (no enhanced recovery programme)

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described

Hong Kong b 2009

Methods

Two-centre RCT

Hong Kong, China

Number of patients assessed for eligibility but not randomised unknown

Inclusion period: September 1993 to October 2002

Participantsn = 153 (LTME n = 76; OTME n = 77)
Inclusion criteria: upper rectal cancer
Exclusion criteria: distance from anal verge < 5 cm, tumour size > 6 cm, T4 rectal cancer, previous abdominal operations in lower pelvis, intestinal obstruction or perforation, metastatic disease, no informed consent
Age (y): 66.5 vs 65.7 (mean)
Dukes stage (%): A 14 vs 17; B 38 vs 38; C 26 vs 36; D 21 vs 9
Tumour location: Upper rectum 12 - 15 cm
Follow-up: 112.5 vs 108.8 months (median, living participants)
InterventionsLaparoscopic vs open TME
APR (%): 0
LAR (%): 100
Colon (%):0
Adjuvant therapy (%): 14.5 vs 32.5 chemotherapy, 17.1 vs 27.3 radiotherapy
OutcomesPrimary outcome: Long-term morbidity (adhesion-related obstruction, incisional hernia)
Secondary outcomes: Recurrence and survival
Notes

Long-term data upper rectal cancer subgroup of Hong Kong a 2004

Short-term mortality not included in long-term morbidity and mortality analysis

Funding or conflicts of interest: No statement

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskas Hong Kong a 2004
Allocation concealment (selection bias)Low riskas Hong Kong a 2004
Incomplete outcome data (attrition bias)
All outcomes
Low riskLoss to follow-up described, intention-to-treat analysis
Selective reporting (reporting bias)Low riskLow diversity with upper rectal subgroup
Other biasHigh riskas Hong Kong a 2004
Blinding of participants and personnel (performance bias)
All outcomes
Low riskas Hong Kong a 2004
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described

Hong Kong c 2000

Methods

Single-centre RCT

Hong Kong, China
Number of patients assessed for eligibility but not randomised unknown

Inclusion period: September 1996 to April 1998

Participantsn = 34 (LTME n = 17 ; OTME n = 17 )
Inclusion criteria: sigmoid and upper rectal cancer
Exclusion criteria: distance from anal verge < 5 cm, tumour size > 6 cm, T4 rectal cancer, previous abdominal operations in lower pelvis, intestinal obstruction or perforation, metastatic disease, no informed consent
Age (y): 67.0 vs 66.9 (mean)
Dukes stage (%): A 0 vs 0; B 59 vs 53; C 41 vs 47; D 0 vs 0
Tumour location: sigmoid and rectum
Follow-up: 22.6 vs 20.5 months (median)
InterventionsLaparoscopic vs open
APR (%): 0
LAR (%): 100
Colon (%):0
OutcomesPrimary outcome: cytokine and CRP response
Notes

Smaller subgroup rectosigmoid Hong Kong a 2004

Funding or conflicts of interest: No statement

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskas Hong Kong a 2004
Allocation concealment (selection bias)Low riskas Hong Kong a 2004
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing data reported, intention-to-treat analysis
Selective reporting (reporting bias)Low riskSample size calculated
Other biasHigh risk

High diversity with sigmoid and rectum carcinoma, ratio not given
Low conversion rate compared to Hong Kong a 2004

Surgeon's experience: "Skilled in both laparoscopic and open colorectal surgery"

Blinding of participants and personnel (performance bias)
All outcomes
Low riskas Hong Kong a 2004
Blinding of outcome assessment (detection bias)
All outcomes
Low riskObjective measurements

Hong Kong d 2003

Methods

Single-centre RCT

Hong Kong, China
Number of patients assessed for eligibility but not randomised unknown

Inclusion period: June 1998 to August 1999

Participantsn = 40 (LTME n = 20; OTME n = 20)
Inclusion criteria: sigmoid and upper rectal cancer
Exclusion criteria: distance from anal verge < 5 cm, tumour size > 6 cm, T4 rectal cancer, previous abdominal operations in lower pelvis, intestinal obstruction or perforation, metastatic disease, no informed consent
Age (y): 68.2 vs 69.1 (mean)
Dukes stage (%): A 5 vs 5, B 50 vs 55, C 45 vs 40, D 0 vs 0
Tumour location: sigmoid and rectum
Follow-up: 8 days
InterventionsLaparoscopic vs open
APR (%): 0
LAR (%): 100
Colon (%):0
OutcomesPrimary outcome: lymphocyte subpopulation and natural killer cell cytotoxicity
Notes

Smaller subgroup rectosigmoid Hong Kong a 2004

Funding or conflicts of interest: No statement

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskas Hong Kong a 2004
Allocation concealment (selection bias)Low riskas Hong Kong a 2004
Incomplete outcome data (attrition bias)
All outcomes
Low riskno missing data reported, intention-to-treat analysis
Selective reporting (reporting bias)Low riskSample size calculated
Other biasHigh risk

High diversity rectosigmoid carcinoma, ratio not given

Surgeon's experience: "Skilled in both laparoscopic and open colorectal surgery"

Blinding of participants and personnel (performance bias)
All outcomes
Low riskas Hong Kong a 2004
Blinding of outcome assessment (detection bias)
All outcomes
Low riskObjective measurements

Kang 2010

Methods

Multicenter RCT (3 centres)

Seoul, South Corea
Number of patients assessed for eligibility but not randomised: 39

Inclusion period: April 2006 to August 2009

Participantsn = 340 (LTME n = 170; OTME n =170)
Inclusion criteria: Mid and low rectal cancer, after preoperative chemoradiation
Exclusion criteria: Distant metastasis, another malignancy, severe cardiac or pulmonary disease, pregnancy, severe medical disease, intestinal obstruction or perforation
Age (y): 57.8 vs 59.1 (mean)
Dukes stage (%): unknown (cT3 N0-2 M0)
Tumour location: mid or lower rectum < 9cm
Follow-up: 3 months
Response rate for questionnaire 75% vs 77%
InterventionsLaparoscopic vs open TME
APR (%): 11.2 vs 14.1
LAR (%): 88.8 vs 85.9
Colon (%): 0
Neoadjuvant therapy: All neoadjuvant chemoradiotherapy and recommended 4 months adjuvant therapy
OutcomesPrimary outcome: 3-year disease-free survival
Secondary outcomes: TME quality, CRM, lymph nodes, distance anal verge, surgical time, length of incision, tumour size, gastrointestinal recovery, hospital stay, complications, quality of life
Notes

Long-term data expected in 2013

Funding or conflicts of interest: National cancer centre, South Corea. The authors declared no conflicts of interest

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskTelephone trial co-ordinator, block permutation approach
Allocation concealment (selection bias)Unclear riskTelephone trial co-ordinator, moment of randomisation unknown
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo loss to follow-up, intention-to-treat analysis
Selective reporting (reporting bias)Low risk

No missing data

Sample size calculation performed

Other biasLow riskLow diversity with mid/low rectal cancer cT3N0-2
Surgeon's experience: median 75 laparoscopic resections (28 - 150), live demonstrations and video assessment
Blinding of participants and personnel (performance bias)
All outcomes
Low risk

Surgical procedure according to TME

Standardised postoperative protocol, no enhanced recovery

Blinding of outcome assessment (detection bias)
All outcomes
Low riskPathologists blinded

King 2006

Methods

Single-centre RCT

Yeovil, United Kingdom
Number of patients assessed for eligibility but not randomised: 32

January 2002 to March 2004

Participantsn = 62 (LTME n = 41; OTME n = 19) (rectal n = 19)
Inclusion criteria: adenocarcinoma of the colon or rectum
Exclusion criteria:Non-elective admission, distant metastases, age < 18, pregnancy, no informed consent, unsuitable for epidural anaesthesia (from 2nd year on)
Age (y): 72.3 vs 70.4 (mean)
Dukes stage (%): A 22.0 vs 5.3; B 46.3 vs 57.9; C 31.7 vs 36.8
Tumour location: colon and rectum
Follow-up: 6 weeks/12 months
Compliance rate for HRQL questionnaires over 95% and response rate of 80%
InterventionsLaparoscopic vs open TME
APR (%): 7.3 vs 5.3
LAR (%): 29.3 vs 21.1
Colon (%): 63.4 vs 73.7
Neoadjuvant therapy:12% neoadjuvant chemotherapy, 35% adjuvant chemotherapy
OutcomesPrimary outcome: Hospital stay
Secondary outcomes: Morbidity, analgesia requirement, antiemetic requirement, re-admission stay, quality of life, cost, disease recurrence, stoma closure, adjuvant chemotherapy, health-related quality of life and functional outcomes
Study-specific questionnaire for functional recovery
Notes

Funding or conflicts of interest: National Health Service Developments in the Organization of Care Projects Grant.

Yeovil District Hospital has received funds from Ethicon Endosurgery to support postgraduate training in
laparoscopic surgery. One author is supported by a Medical Research Council Clinician Scientist Award.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated sequence
Allocation concealment (selection bias)Unclear riskTelephone trial co-ordinator, moment of randomisation unclear
Incomplete outcome data (attrition bias)
All outcomes
Low riskLoss to follow-up described, intention-to-treat analysis
Selective reporting (reporting bias)Low risk

Data reported according to methods described

No sample size for these outcomes calculated

Other biasUnclear risk

High diversity, all colorectal patients

Single surgeon, experience unknown

Blinding of participants and personnel (performance bias)
All outcomes
Low risk

Surgical procedure described according to TME

Postoperative protocol according to enhanced recovery programme

Blinding of outcome assessment (detection bias)
All outcomes
Low riskData collection team

Liang 2011

Methods

Single-centre RCT

Taiyuan, China

Number of patients assessed for eligibility but not randomised: 3

Inclusion period: May 2004 and April 2008

Participants

n = 343 (LTME n = 169; OTME n = 174)

Inclusion criteria: rectal cancer confirmed by pathological examination, written informed consent. Suitable for LAR or APR.

Exclusion criteria: metastatic disease, BMI > 30, acute intestinal obstruction, previous abdominal surgery, neoadjuvant chemotherapy

Age (y): 57.3 vs 57.4 (mean)

Dukes stage (%): A 5.3 vs 4.0; B 42.6 vs 48.3; C 52.1 vs 47.7; D 0 vs 0

Tumour location: rectum

Follow-up: 44 months (median)

Interventions

Laparoscopic versus open TME

APR (%): 49.1 vs 40.2

LAR (%): 50.9 vs 59.8

Colon(%): 0

(neo)adjuvant therapy: neoadjuvant excluded, adjuvant unknown

Outcomes

Primary outcome: 3-year survival

Secondary outcomes: Number of lymph nodes removed, length of specimen, distance between inferior border of tumour and incised margin in LAR, time to first discharge, bowel movement and fluid intake, infectious complications, anastomotic leakage, anastomotic stenosis, deep vein thrombosis, 1-year survival

NotesFunding or conflicts of interest: No competing financial interests declared
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomisation not mentioned
Allocation concealment (selection bias)Low riskSealed opaque envelopes, day before surgery
Incomplete outcome data (attrition bias)
All outcomes
Low riskLoss to follow-up described, intention-to-treat analysis
Selective reporting (reporting bias)High riskSample size calculation not performed
Other biasUnclear risk

Distance for anal verge unknown

Single surgical team

Blinding of participants and personnel (performance bias)
All outcomes
Low risk

Surgical procedure not described, TME principles followed

Standardised postoperative protocol (no enhanced recovery programme)

Blinding of outcome assessment (detection bias)
All outcomes
Low riskComplications assessed by reviewer unaware of treatment group

Liu 2010

Methods

Single-centre RCT

Hangzhou, China
Number of patients assessed for eligibility but not randomised unknown

Inclusion period: February 2005 and October 2008

Participantsn = 186 (LTME n = 98; OMTE n = 88)
Inclusion criteria: rectal carcinoma
Exclusion criteria: synchronous cancer, acute intestinal obstruction or perforation
Age (y): 59.3 vs 61.5 (mean)
Dukes stage (%): A 32.7 vs 28.4 B 35.7 vs 34.1 C 27.6 vs 26.1D 4.1 vs 11.4
Tumour location: rectum
Follow-up: 16.3 months (mean)
InterventionsLaparoscopic vs open TME, hand-assisted
APR (%): 12.2 vs 15.9
LAR (%): 83.7 vs 79.5
Colon (%): 0
Neoadjuvant therapy: unknown
OutcomesPrimary outcome: "safety and efficacy"
Secondary outcomes: Duration of surgery, incision length, blood loss, analgesia requirement, time to flatus, time to oral fluids, hospital stay, complications, number of lymph nodes
Notes

Hand-assisted laparoscopy

Funding or conflicts of interest: The authors declared no conflicts of interest in relation to this article

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated randomisation
Allocation concealment (selection bias)High riskUnknown
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskLoss to follow-up not described, intention-to-treat irrelevant with no conversions
Selective reporting (reporting bias)High riskSample size calculation not performed
Other biasUnclear risk

Distance from anal verge unknown

Single surgical team, experience unknown

Blinding of participants and personnel (performance bias)
All outcomes
High risk

Surgical procedure described, TME unknown

No standardised postoperative protocol

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described

Lujan 2009

Methods

Single-centre RCT

Murcia, Spain
Number of patients assessed for eligibility but not randomised: 31

Inclusion period: January 2002 and February 2007

Participantsn = 204 (LTME n = 103; OTME n = 101)
Inclusion criteria: Mid and low rectal adenocarcinoma
Exclusion criteria: Locally advanced disease, FAP, emergency surgery
Age (y): 67.8 vs 66.0 (mean)
Dukes stage (%): A 10.9 vs 14.6 B 34.7 vs 37.9 C 44.6 vs 42.7 D 9.9 vs 4.9
Tumour location: rectum < 9cm
Follow-up: 32.8 vs 34.1 months (mean)
InterventionsLaparoscopic vs open TME
APR (%): 23.8 vs 21.4
LAR (%): 76.2 vs 78.6
Colon (%): 0
Neoadjuvant therapy: Stage II and III neoadjuvant chemoradiotherapy, stage III and IV adjuvant chemotherapy
Outcomes

Primary outcome: number of lymph nodes harvested

Secondary outcomes: 2- and 5-year local recurrence, survival, circumferential margin involvement, complication rate, hospital stay

NotesFunding or conflicts of interest: The authors declare no conflicts of interest
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer generated randomisation
Allocation concealment (selection bias)Low riskSealed envelope until day of operation
Incomplete outcome data (attrition bias)
All outcomes
Low riskLoss to follow-up described, intention-to-treat
analysis
Selective reporting (reporting bias)Unclear risk

Non-radical resections excluded from analysis

Sample size calculation performed

Other biasUnclear riskSingle surgical team, experience unknown
Blinding of participants and personnel (performance bias)
All outcomes
Low riskSurgical procedure described according to TME
Standardised postoperative protocol within
enhanced recovery program
Blinding of outcome assessment (detection bias)
All outcomes
Low riskSingle experienced pathologist

MRC CLASICC a 2005

Methods

Multicenter RCT (27 centres)
United Kingdom
Number of patients assessed for eligibility but not randomised unknown

Inclusion period: July 1996 to July 2002

Participantsn = 794 (381 rectal LTME n = 253; OTME n = 128 )
Inclusion criteria: Colorectal carcinoma suitable for right hemicolectomy, left hemicolectomy, sigmoid, anterior resection, APR
Exclusion criteria: Transversum, cardiac or pulmonary disease, acute intestinal obstruction, other malignant disease in past 5 years, synchronous adenocarcinoma, pregnancy, associated GI disease needing surgical intervention
Age (y): 69 vs 69 (mean)
Dukes stage (%): A 16.7 vs 16.4; B 34.6 vs 36.9 C 37.1 vs 34.7
Tumour location: colon and rectum
Follow-up: 3 months, 3 years ,5 years and 10 years
InterventionsLaparoscopic vs open colorectal surgery
APR (%): 13 vs 12
LAR (%): 37 vs 36
Colon (%): 50 vs 52
Neoadjuvant therapy(%): Adjuvant radiotherapy 5.5 vs 6.7 and adjuvant chemotherapy 28.1 vs 28.7
OutcomesPrimary outcomes: resection margins, Dukes C2 tumours, in-hospital mortality, 3 and 5 year OS/DFS and local recurrence
Secondary outcomes: Complication rates, quality of life, transfusion requirements, distant and port site recurrences at 3 and 5 years, short term costs
Notes

Short term results, short-term costs, 3-year, 5-year and 10-year data of the CLASICC Trial across 5 different publications.
No reply to request for additional data for meta-analysis

Funding or conflicts of interest: The authors declare to have no conflict of interest. The trial was funded by the UK Medical Research Council.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskTelephone trial co-ordinator, stratified by surgeon, site of surgery, presence of metastases and preoperative radiotherapy
Allocation concealment (selection bias)Low riskTelephone trial co-ordinator
Incomplete outcome data (attrition bias)
All outcomes
Low riskLoss to follow-up and missing data described, intention-to-treat analysis
Selective reporting (reporting bias)High risk

High rate of missing participant and pathological data, up to 13%

Sample size calculation performed, but not reached

Other biasLow risk

High diversity with colorectal cancer patients, specific rectal cancer data published separately

Surgeons' experience: a minimum of 20 laparoscopic resections

Blinding of participants and personnel (performance bias)
All outcomes
High riskSurgical procedure according to surgeons current practice
No standardised postoperative protocol described, enhanced recovery unknown
Blinding of outcome assessment (detection bias)
All outcomes
Low riskData monitoring committee

MRC CLASICC b 2005

Methods

Multicenter RCT (27 centres)
United Kingdom
Number of patients assessed for eligibility but not randomised unknown

Inclusion period: July 1996 to July 2002

Participantsn = 148 (LTME n = 98; OTME n =50), n = 347 including laparoscopic colon group
Age (y): 66 vs 65 (mean)
Questionnaire response rate 71.2% of 347 participants eligible for inclusion
Tumour location: rectum > 5 cm
InterventionsLaparoscopic colon versus laparoscopic rectal versus open rectal
OutcomesPrimary outcome: Overall function score for sexual and bladder function
I-PSS, IIEF, FSFI questionnaires over the last 4 weeks at a single time point within or after 12 months (up to 76 months)
EORTC module QLQ-CR38 questionnaire items at 2 weeks and 3, 6, 18 months
Notes

Subgroup of MRC CLASICC a 2005

Converted patients analysed as open surgery
Some comparisons only between laparoscopic rectal and laparoscopic colon

Funding or conflicts of interest: No statement

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskas MRC CLASICC a 2005
Allocation concealment (selection bias)Low riskas MRC CLASICC a 2005
Incomplete outcome data (attrition bias)
All outcomes
High riskNo intention-to-treat analysis
Selective reporting (reporting bias)High risk

Most data only addressed in text, numbers not given

Sample size calculated for questionnaire outcome

Other biasUnclear riskNo other bias identified
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskUnknown
Blinding of outcome assessment (detection bias)
All outcomes
Low riskValidated questionnaires

MRC CLASICC c 2001

Methods

Single-centre RCT

Singapore
Number of patients assessed for eligibility but not randomised unknown

Inclusion period: March 1997 to August 1999

Participantsn = 236 (LTME n = 118; OTME n = 118)
Inclusion criteria: > 18 y, elective surgery, left hemi colon, sigmoid or rectum
Exclusion criteria: transverse colon, contraindication for pneumoperitoneum, acute intestinal obstruction, any malignancy in previous 5 y, synchronous adenocarcinomas and pregnancy
Age (y): 64 vs 62 (median)
Gender (%): male 52 vs 59
Dukes stage (%): A 8 vs 7; B 41 vs 45; C 38 vs 38; D 13 vs 10
Tumour location: colon and rectum
Follow-up: 3 days for immune response
InterventionsLaparoscopic vs open colorectal surgery
APR (%): 85 vs 85
AR (%): 6 vs 5
Colon (%):9 vs 10
Neoadjuvant treatment: unknown
OutcomesPrimary outcome: T-cell number
Secondary outcomes: CD4, CD8, humoral response, complement level, phagocytosis function
Notes

Singapore subgroup MRC CLASICC a 2005

Funding or conflicts of interest: Funding by the National Reseach Council Singapore, no statement on conflict of interest.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskCentral telephone randomisation
Allocation concealment (selection bias)Low riskBlocks of 6 and 4
Incomplete outcome data (attrition bias)
All outcomes
Low risk

Intention-to-treat analysis, missing data addressed

Sample size calculation performed

Selective reporting (reporting bias)High riskHigh rate of missing data (12 participants preoperative, 44 postoperative)
Other biasUnclear risk

1:1 randomisation, in contrast to 2:1 randomisation in CLASICC Trial

Surgeons' experience as MRC CLASICC a 2005 > 20 procedures

Blinding of participants and personnel (performance bias)
All outcomes
Low riskSurgical procedure described according to TME
Blinding of outcome assessment (detection bias)
All outcomes
Low riskObjective measurements

Ng 2008

Methods

Single-centre RCT

Hong Kong, China
Number of patients assessed for eligibility but not randomised: 54

Inclusion period: September 1994 to February 2005

Participantsn = 99 (LTME n = 51; OTME n = 48)
Inclusion criteria: Low rectal cancer, eligible for APR
Exclusion criteria: Tumour > 6 cm, clinical infiltrative cancer, recurrent disease, no informed consent, intestinal obstruction or perforation
Age (y): 63.7 vs 63.5 (mean)
Dukes stage (%): A 5 vs 4; B 6.5 vs 4; C 8.5 vs 10; D 5.5 vs 6
Tumour location: low rectal cancer < 5 cm
Follow-up 87.2 vs 90.1 months (median, participants alive)
InterventionsLaparoscopic vs open TME
APR (%): 100
LAR (%): 0
Colon (%):0
Neoadjuvant therapy not offered, adjuvant unknown
OutcomesPrimary outcome: Analgesic requirement and postoperative recovery
Secondary outcomes: Recurrence and survival at 5 years
Operative time, blood loss, disposable instruments, transfusion, analgesic requirement, pain score, time to flatus, time to bowel movement, time to diet, time to walk independently, hospital stay, morbidity, mortality, circumferential margin involvement, lymph nodes
Notes

Low and mid rectal cancer subgroup

Funding or conflicts of interest: No statement

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated sequence
Allocation concealment (selection bias)Low riskKept concealed by an independent operating theatre co-ordinator
Incomplete outcome data (attrition bias)
All outcomes
Low riskIntention-to-treat analysis, loss to follow-up described
Selective reporting (reporting bias)Low risk

Follow-up for participants alive

Sample size calculation performed

Other biasLow riskSurgeons' experience: "surgeons experienced in both laparoscopic and colorectal surgery"
Blinding of participants and personnel (performance bias)
All outcomes
Low risk

Surgical procedure, TME unknown

Standardised postoperative protocol, no enhanced recovery

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described

Pechlivanides 2007

Methods

Multicenter RCT (3 centres)

Crete and Athens, Greece
Number of patients assessed for eligibility but not randomised unknown

Inclusion period: unknown

Participantsn = 73 (LTME n = 34; OTME n = 39)
Inclusion criteria: low rectal carcinoma < 12 cm
Exclusion criteria: Tumours extending to the pelvic walls or organs
Age (y): 72 vs 69 (median)
Dukes stage (%): only T stage given
Tumour location: mid and low rectal carcinoma < 12 cm
Follow-up: no follow-up
InterventionsLaparoscopic vs open TME
APR (%): 20.6 vs 10.3
LAR (%):79.4 vs 89.7
Colon (%): 0
(Neo) adjuvant therapy: Short-course radiotherapy or long-course chemoradiation
OutcomesPrimary outcome: Oncological clearance (number of lymph nodes)
Secondary outcomes: pathological stage, extent of tumour invasion
NotesFunding or conflicts of interest: No statement
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated numbers
Allocation concealment (selection bias)High riskUnknown
Incomplete outcome data (attrition bias)
All outcomes
High risk

Loss to follow-up and intention-to-treat not described

Only one outcome

Limited details on inclusion and exclusion criteria

Selective reporting (reporting bias)Unclear riskNo sample size calculation
Other biasHigh risk

Significantly less anastomoses and more ileostomies in the laparoscopic group

Surgeon's experience: "most experienced surgeon"

Blinding of participants and personnel (performance bias)
All outcomes
Low risk

Surgical procedure described according to TME

Postoperative protocol irrelevant for outcome

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo blinding described

Zhou 2004

Methods

Single-centre RCT

Sichuan, China
Number of patients assessed for eligibility but not randomised unknown

Inclusion period: June 2001 to September 2002

Participantsn = 171 (LTME n = 82; OMTE n = 89)
Inclusion criteria: primary rectal cancer with lowest margin of tumour located under the peritoneal reflection and 1.5 cm above the dentate line
Exclusion criteria: rectal cancer of other pathological type (e.g. lymphoma), emergency surgery, Dukes D tumours with local infiltration affecting adjacent organs, participants unwilling to take part in the study
Age (y): 45 vs 44 (mean)
Dukes stage (%): A 6 vs 7; B 12 vs 9; C 77 vs 76; D 5 vs 8
Tumour location: mid and low rectal cancer (lowest margin 1 - 8 cm)
Follow-up: range 1 - 16 months
InterventionsLaparoscopic vs open TME
APR (%): 0
LAR (%): 100
Colon (%):0
(Neo)adjuvant therapy: not described
OutcomesPrimary outcome: Feasibility and efficacy and short-term outcomes
Morbidity, mortality, duration of surgery, blood loss, analgesia requirement, time to flatus, time to intake, time to defecation, pain score, hospital stay
NotesFunding or conflicts of interest: Funded by a National Outstanding Youth Foundation of China grant
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskThe grouping was randomised
Allocation concealment (selection bias)High riskNot described
Incomplete outcome data (attrition bias)
All outcomes
High riskLoss to follow-up and intention-to-treat analysis unknown, conversion rate unknown
Selective reporting (reporting bias)High riskNo sample size calculation
Other biasUnclear riskSurgeons' experience: 4 colorectal surgeons, experience unknown
Blinding of participants and personnel (performance bias)
All outcomes
High riskNo standardised postoperative protocol described
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described

Zhou 2007

  1. a

    APR: abdominoperineal resection
    AR: anterior resection
    ASA: American Society of Anaesthesiologists
    CI: Confidence interval
    CRP: C-reative protein
    CT: computed tomography
    EORTC: European Organization for the Research and Treatment of Cancer
    FAP: familial adenomatous polyposis
    FSFI: Female sexual function index
    HLA-DR: Human Leukocyte Antigen D related
    HNPCC: hereditary non-polyposis colorectal cancer
    HRQL: health-related quality of life
    IIEF: Internation index of erectile function
    I-PSS: International prostate symptom score
    LAR: lower anterior resection
    MRI: magnetic resonance imaging
    QLQ-CR38: Quality of life questionnaire - colorectal cancer-specific
    TME: total mesorectal excision
    VAS: visual analogue scale
    WBC: white blood cells

Methods

Single-centre RCT

Shijiazhuang, China
Number of patients assessed for eligibility but not randomised unknown, but 4 excluded after randomisation

Inclusion period: December 2004 to April 2007

Participantsn = 71 (LTME n = 36; OTME n = 35)
Inclusion criteria: Histologically confirmed rectal cancer, suitable for elective surgery
Exclusion criteria: Neoadjuvant treatment, metastases, postoperative anastomotic leakage
Age (y): 56 vs 55 (mean)
Dukes stage (%): A 6 vs 6; B 47 vs 43; C 47 vs 51
Tumour location: rectal cancer > 5 cm
Follow-up: 5 days
InterventionsLaparoscopic vs open TME
APR (%): 0
LAR (%): 100
Colon (%): 0
Neoadjuvant therapy is exclusion criteria
Outcomes

Primary outcome not stated

Outcomes: Body temperature, WBC count, CRP level, Cortisol level, IL-6 level, VAS score at -1, 1, 3 and 5 days

Notes

Article translated from Chinese

Funding or conflicts of interest: Science and Research Fund of The Second Hospital of Hebei Medical University

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandom allocation
Allocation concealment (selection bias)Unclear riskUnknown
Incomplete outcome data (attrition bias)
All outcomes
High riskConversion and intention-to-treat unknown
Selective reporting (reporting bias)Unclear riskNo sample size calculation
Other biasHigh riskSurgeon's experience: unknown
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskUnknown
Blinding of outcome assessment (detection bias)
All outcomes
Low riskObjective measurements

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Braga 2002Colorectal benign disease included, extended subgroup of rectal cancer participants described in Braga 2007
Braga 2005Data on colorectal participants, extended subgroup of rectal cancer participants described in Braga 2007
JCOG 0404 2005Colon cancer including rectosigmoid, rectal cancer excluded.
Kim 1998Mid and low rectum excluded, number of upper rectum within proctosigmoid group unclear.
LaFa 2011Unknown number of rectal cancer participants included (anterior resection, left and right colectomy)
LAPKON II 2009Colorectal participants, unknown number of rectal carcinoma > 12 cm included.
Leung 1999Only partially randomised and no intention-to-treat analysis
Liu 2009No TME performed (D3 lymphadenectomy)
Milsom 1998Benign disease included, no separate analysis on rectal cancer.
Mirza 2008Almost all participants were randomised within 2 other trials (MRC CLASICC a 2005; King 2006), not fully randomised
Morris 2011Comparison between CLASICC Trial data and national registry
Pan 2007Surgeon in steep learning curve during study. Significant differences in outcome between early and late inclusion groups. No numerical outcomes provided in abstract, no full-text available.
Polle 2007Benign disease and familial polyposis coli participants included
Schwenk 1998Sphincter-preserving resection with TME is exclusion criterion
Stead 2000Economic comparison between UK and USA trials
Yamamoto 2008Non-randomised, single arm phase II trial

Characteristics of ongoing studies [ordered by study ID]

ACTRN12609000663257

Trial name or titleA La CaRT: Australasian Laparoscopic Cancer of the Rectum Trial A phase III prospective randomised trial comparing laparoscopic-assisted resection versus open resection for rectal cancer
MethodsRandomised controlled trial
Target sample size: 470
Participants

Inclusion criteria: Histological diagnosis of adenocarcinoma of the rectum (<15cm from the anal verge as measured by rigid sigmoidoscopy), T 1-3 N0 M0, T1-3 N1 M0 or T1-3 N0-1 M1 disease as determined by pre-treatment CT scans and pelvic MRI or EUS. For patients with T3 or N1 disease, completion of pre-operative 5FU-based chemotherapy and/or radiation therapy. Capecitabine may be substituted for 5FU, Age >18 years, ECOG Performance Status: 0, 1 or 2, Written informed consent, Life expectancy of at least 12 weeks.

Exclusion criteria: Medical or psychiatric conditions that compromise the patient's ability to give informed consent or comply with the study protocol. Pregnancy or breast feeding. Any uncontrolled concurrent medical condition. Any co-morbid disease that would increase risk of morbidity. Participation in any investigational drug study within the previous 4 weeks. Evidence of T4 disease extending to circumferential margin of rectum or invading adjacent organs. Evidence of systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude surgery, or other severe incapacitating disease, ASA IV or ASA V. History of conditions that would preclude use of a laparoscopic approach (e.g. multiple previous major laparotomies, severe adhesions). Concurrent or previous invasive pelvic malignancy (cervical, uterine and rectal) within five years prior to registration.

InterventionsLaparoscopic-assisted resection versus open resection
OutcomesTo determine whether laparoscopic-assisted resection is not inferior to open rectal resection as a safe, effective oncologic approach to rectal cancer and secondary from a patient related benefit perspective, based on morbidity, mortality associated with surgery, disease-free survival and disease recurrence and quality of life
Starting dateMarch 2010
Contact informationDr. Andrew Stevenson, c/o A La CaRT Trial Coordinator NHMRC Clinical Trials Centre Locked Bag 77, Camperdown, 1450, Australia. alacart@ctc.usyd.edu.au
NotesPatient recruitment ongoing

NCT00726622

Trial name or titleA phase III prospective randomized trial comparing laparoscopic-assisted resection versus open resection for rectal cancer - ACOSOG Z6051
MethodsRandomised controlled trial
Target sample size: 650
Follow-up 5 years
ParticipantsInclusion: Histologically confirmed adenocarcinoma of the rectum (<12 cm from the anal verge), T3, N0, M0 or T1-3, N1-2, M0 disease by pre-neoadjuvant therapy CT scans and pelvic MRI or transrectal ultrasound. Completed neoadjuvant fluorouracil-based chemotherapy and/or radiotherapy within the past 4 weeks (Capecitabine may have been substituted for fluorouracil), ECOG performance status 0 - 2,
Exclusion: T4 disease, severe incapacitating disease (i.e., ASA IV or ASA V), systemic disease (e.g., cardiovascular, renal, or hepatic) that would preclude surgery, evidence of conditions (e.g., multiple prior major laparotomies or severe adhesions) that would preclude use of a laparoscopic approach, pregnancy, Body mass index > 34, other invasive pelvic malignancy (cervical, uterine, or rectal) within the past 5 years, history of psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
InterventionsLaparoscopic versus open rectal surgery
OutcomesPrimary outcomes: Circumferential margin > 1 mm, Distal resected margin > 2 cm (or > 1 cm with clear frozen section in the low rectum), Completeness of total mesorectal excision
Secondary outcomes: Patient-related benefit, disease-free survival (2 years), Local pelvic recurrence rates, overall survival, quality of life, sexual function and bowel function.
Starting dateAugust 2008
Contact informationJames Fleshman, MD. American College of Surgeons Oncology Group. fleshman@wustl.edu
NotesPatient recruitment ongoing until Dec 2013

Ancillary