Adjuvant Therapy for completely resected Stage II Colon Cancer

  • Review
  • Intervention

Authors

  • Alvaro Figueredo,

    Corresponding author
    1. Dept. of Clin. Epid. and Stat.,, Hamilton Regional Cancer Centre, McMaster Univ., Hamilton, Ontario, Canada
    • Alvaro Figueredo, Hamilton Regional Cancer Centre, McMaster Univ., Dept. of Clin. Epid. and Stat.,, 699 Concession Street, Hamilton, Ontario, L8V 5C2, Canada. alvaro.figueredo@hrcc.on.ca.

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  • Megan E Coombes,

    1. Faculty of Health Sciences, McMaster University, Juravinski Cancer Centre, Departement of Oncology, Hamilton, Ontario, Canada
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  • Som Mukherjee

    1. Faculty of Health Sciences, McMaster University, Juravinski Cancer Centre, Departement of Oncology, Hamilton, Ontario, Canada
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Abstract

Background

: Colon cancer is potentially curable by surgery. Although adjuvant chemotherapy benefits patients with stage III disease, there is uncertainty of such benefit in stage II colon cancer. A systematic review of the literature was performed to better define the potential benefits of adjuvant therapy for patients with stage II colon cancer.

Objectives

: To determine the effects of adjuvant therapy on overall survival and disease-free survival in patients with stage II colon cancer.

Search methods

: Ovid MEDLINE(R) (1986-2007), EMBASE (1980-2007), and EBM Reviews - Cochrane Central Register of Controlled Trials ( to 2007) were searched using the medical headings "colonic neoplasms", "colorectal neoplasms", "adjuvant chemotherapy", "adjuvant radiotherapy" and "immunotherapy", and the text words "colon cancer" and "colonic neoplasms". In addition, proceedings from the annual meetings of the American Society of Clinical Oncology and the European Society of Medical Oncology (1996 to 2004) as well as personal files were searched for additional information.

Selection criteria

: Randomized trials or meta-analyses containing data on stage II colon cancer patients undergoing adjuvant therapy versus surgery alone.

Data collection and analysis

: Three reviewers summarized the results of selected studies. The main outcomes of interest were overall and disease-free survival, however, data on toxicity and treatment delivery were also recorded.

Main results

: With regards to the effect of adjuvant therapy on stage II colon cancer, the pooled relative risk ratio for overall survival was 0.96 (95% confidence interval 0.88, 1.05). With regards to disease-free survival, the pooled relative risk ratio was 0.83 (95% confidence interval 0.75, 0.92).

Authors' conclusions

: Although there was no improvement in overall survival in the pooled analysis, we did find that disease-free survival in patients with stage II colon cancer was signficantly better with the use of adjuvant therapy. It seems reasonable to discuss the benefits of adjuvant systemic chemotherapy with those stage II patients who have high risk features, including obstruction, perforation, inadequate lymph node sampling or T4 disease. The co-morbidities and likelihood of tolerating adjuvant systemic chemotherapy should be considered as well. There exists a need to further define which high-risk features in stage II colon cancer patients should be used to select patients for adjuvant therapy. Also, researchers must continue to search for other therapies which might be more effective, shorter in duration and less toxic than those available today.

摘要

背景

第二期大腸癌完全切除術後的輔助性療法

大腸癌可能經手術而治愈。雖然輔助性化療對第三期患者有益,但是並不確定第二期大腸癌是否亦能受益。因此進行一項系統性的文獻回顧,明確界定輔助性療法對第二期大腸癌病患的可能益處

目標

確定輔助性療法對第二期大腸癌患者整體存活率,以及無病存活率的作用

搜尋策略

採用Ovid MEDLINE(R)(1986年至2007年)、EMBASE(1980年至2007年)以及EBM Reviews �Cochrane Central Register of Controlled Trials(至2007年),搜尋醫療標題「大腸腫瘤」、「大腸直腸癌」、「輔助性化療」、「輔助性放射治療」與「免疫療法」,以及搜尋內文含「大腸癌」與「大腸腫瘤」。此外,其他資訊則是從American Society of Clinical Oncology以及European Society of Medical Oncology年度會議(1996年至2004年)的會議紀錄,以及個人檔案中搜尋

選擇標準

隨機分配的臨床試驗(Randomized trials),或包含第二期大腸癌患者進行輔助性療法,相較於單一手術資料的統合分析(metaanalyses)

資料收集與分析

三位檢閱者對選定的研究進行結果的總結。主要關注的結果是總存活率(overall survival)及無病存活率(diseasefree survival),但是亦一併紀錄毒性及治療執行的資料

主要結論

針對輔助性療法對第二期大腸癌的作用,整體存活率的匯集相對危險比率(the pooled relative risk ratio)為0.96(95%CI 0.88−1.05);而無病存活率的匯集相對危險比率為0.83(95%CI 0.75−0.92)

作者結論

雖然整體存活率的匯集分析(the pooled analysis)並無改善的情況,但我們確實發現,進行輔助性療法第二期大腸癌患者的無病存活率明顯更佳。因此,合理認為應向有高風險特徵包括阻塞、穿孔、淋巴結取樣不足或T4疾病的第二期患者,討論輔助性系統化療的益處。需要進一步界定,應該以哪些第二期大腸癌患者的高風險特徵選擇輔助性療法的病患。另外,研究人員必須繼續尋找其他較目前的治療可能更為有效、期間更短,以及更低毒性的療法

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌

總結

第二期大腸癌完全切除術後的輔助性療法 在西方國家,大腸癌是第二常見的癌症死因。大部分大腸癌患者可僅施行手術切除而治愈。對於那些罹患淋巴結陽性(第三期)疾病的患者,復發率可超過50%,並且已證明輔助性化療能大幅降低復發的風險。而無淋巴結轉移(第一及第二期)的患者,單施以手術即有很不錯的預後,其5年存活率為 75%至95%。不過,一些高危險第二期患者的復發率,接近第三期的大腸癌患者。由於全身性化療對第三期疾病的效果,因此考慮對第二期疾病的患者進行類似的做法。我們進行一項系統性回顧,針對所有隨機分配的臨床試驗,評估第二期大腸癌患者以及輔助性療法,相較於單純手術。我們的回顧發現,輔助性療法-全身性或區域性化療或免疫療法,能改善第二期患者的治療成果。輔導個別病患時,提供的意見應視病患的年齡及合併症調整。此外,當衡量全身性治療對第二期大腸癌患者的益處時,也應考慮腫瘤的高風險特徵。需要進一步研究闡明哪些病患及腫瘤的因素,可作為選擇進行第二期大腸癌患者的輔助性療法。另亦需要繼續尋找較目前的治療可能更有效、期間更短,以及更低毒性的輔助性療法

Plain language summary

Adjuvant therapy for completely resected stage II colon cancer

Colon cancer is the second most common cause of cancer deaths in the Western world. A large proportion of colon cancer patients can be cured by surgical resection alone. For those patients with lymph node positive (stage III) disease, the recurrence rate can exceed 50% and adjuvant chemotherapy has been shown to significantly reduce the risk of recurrence. In patients without lymph node involvement (stage I and II), the prognosis is quite good with surgery alone, with survival rates of 75% to 95% at 5 years. However, some patients with high risk stage II disease have a relapse rate approaching that of stage III colon cancer patients. Due to the effectiveness of systemic chemotherapy in stage III disease, a similar approach has been considered for patients with stage II disease. We performed a systematic review looking at all randomized clinical trials evaluating stage II colon cancer patients and adjuvant therapy versus surgery alone. Our review found that adjuvant therapy -either systemic or regional chemotherapy or immunotherapy- can improve the outcomes of stage II patients. In counselling individual patients, the advice given should be conditioned by the patient's age and comorbidities. In addition, the high risk features of the tumour should also be considered when contemplating the benefits of systemic therapy in patients with stage II colon cancer. Further investigation is needed to elucidate which patient and tumour factors can be used to select stage II colon cancer patients for adjuvant therapy. There also exists a need to continue to search for other adjuvant therapies which might be more effective, shorter in duration and less toxic than those available today.

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