Recent updates in the surgical treatment of colorectal cancer

Abstract Because of recent advances in medical technology and new findings of clinical trials, treatment options for colorectal cancer are evolutionally changing, even in the last few years. Therefore, we need to update the treatment options and strategies so that patients can receive optimal and tailored treatment. The present review aimed to elucidate the recent global trends and update the surgical treatment strategies in colorectal cancer by citing the literature published in the last 2 years, namely 2016 and 2017. Although laparoscopic surgery is still considered the most common approach for the treatment of colorectal cancer, new surgical technologies such as transanal total mesorectal excision, robotic surgery, and laparoscopic lateral pelvic lymph node dissection are emerging. However, with the recent evidence, superiority of the laparoscopic approach to the open approach for rectal cancer seems to be controversial. Surgeons should notice the risk of adverse outcomes associated with unfounded and uncontrolled use of these novel techniques. Many promising results are accumulating in preoperative and postoperative treatment including chemotherapy, chemoradiotherapy, and targeted therapy. Development of new biomarkers seems to be essential for further improvement in the treatment outcomes of colorectal cancer patients.

recent advancements is indispensable for the optimal treatment of colorectal cancer patients.
The present study aimed to elucidate recent global trends and update surgical treatment strategies in colorectal cancer by reviewing the literature published in the last 2 years. Several important studies published more recently are also referred to as essential introductory information.

| Laparoscopic versus open approach
Although the previous randomized control trials (RCT) showed the superiority of laparoscopic surgery for colon cancer over open surgery in short-term outcomes, 3,4 there is critical concern about the feasibility of complete mesocolic excision (CME) or D3 dissection in those trials. Just recently, the outcomes of laparoscopic versus open D3 dissection for stage II or III colon cancer in a randomized control trial (JCOG0404) were reported from Japan. 5 In this study, the noninferiority of laparoscopic surgery to open surgery could not be shown because 5-year overall survival (OS) of each group was much better than expected (90.4% for open surgery and 91.8% for laparoscopic surgery, P = .073 for non-inferiority). This result suggests laparoscopic D3 surgery could be an acceptable treatment option for patients with stage II or III colon cancer. A meta-analysis to examine the non-inferiority of laparoscopic CME or D3 surgery versus open surgery was reported from the United Kingdom (UK). 6 In their analysis, there was no difference in short-term mortality and morbidity.
Although intraoperative blood loss was significantly less in the laparoscopic group, there was only a trend for longer operative time and shorter hospital stay in laparoscopic surgery compared to open surgery. There was no significant difference in OS and disease-free survival (DFS). Based on these reports, laparoscopic surgery is considered an acceptable standardized approach for colon cancer even with carrying out CME or D3 dissection.
In contrast, there seems to be some controversy about the noninferiority of laparoscopic surgery to open surgery for rectal cancer (Table 1). Two previous large RCT and several meta-analyses showed   similar pathological and oncological outcomes between laparoscopic and open approaches for rectal cancer, 7-10 and the laparoscopic approach was regarded as a standardized alternative to the open approach. However, two more recent RCT showed contradictory results, and each failed to show the non-inferiority of laparoscopic rectal resection to open rectal resection. 11,12 In the ALaCaRT trial, the number of patients with negative circumferential margin (CRM  A large multicenter study in Japan also showed better short-term outcomes and a lower morbidity rate in the laparoscopic group compared with the open group even in elderly patients with a history of abdominal surgery. 17 They also showed similar oncological outcomes between the groups. These reports suggest that laparoscopic surgery is safe and is the preferred approach for elderly patients with colorectal cancer.

| Robotic surgery
In their systematic review of rectal cancer, Prete et al 18  In an analysis of abdominoperineal resection, robotic surgery had a significantly lower conversion rate compared with laparoscopic surgery (5.7% vs 13.4%; P < .01). 21 However, it had significantly higher total hospital costs compared with laparoscopic surgery (mean difference, US$24 890; P < .01).
Concerning total mesorectal excision (TME) rate, a retrospective analysis of a prospectively maintained database with 20 robotic and 40 laparoscopic surgery cases for rectal cancer was reported. 22 In this study, the quality of TME was better in the robotic group. In a Japanese retrospective study, 203 robotic surgery cases were compared with 239 laparoscopic cases. 23  Rate of urinary retention was significantly lower in the robotic group than in the laparoscopic group (2.5% vs 7.5%, P = .018).
At present, considering the extra financial and time expenses, robotic surgery might be selectively applied for those patients who may benefit from this novel technology.

| Transanal TME
Transanal TME (TaTME) was first introduced by Sylla et al in 2010. 24 Since then, the feasibility and safety of this surgery has been reported by many case studies with acceptable short-term outcomes. [25][26][27][28] Most recently, de Lacy's group reported the pathological results of 186 constitutive cases with mid and low rectal cancer. 29 Complete TME was achieved in 95.7%, and overall positive CRM (≤1 mm) and distal resection margin (DRM) (≤1 mm) were 8.1% and 3.2%, respectively. The international TaTME registry also reported the results of 720 patients. 30  was comparable with that of conventional laparoscopic TME in a previous large RCT. 33 It showed favorable outcomes of low rates of anastomosis leakage (5.7%) and conversion (3.0%). The rate of positive CRM was 4.7%, and complete TME was achieved in 87.6%.
DRM involvement developed in 0.2% only. Importantly, operative and oncological outcomes were better in high-volume centers (>30 cases in total) than in low-volume centers (<30 cases in total) including operative time, conversion rate, major complication rate, TME quality, and local recurrence rate. Currently, a multicenter RCT comparing TaTME versus laparoscopic TME for mid and low rectal cancer (COLOR III) is ongoing. 34 However, technical difficulty of this approach has been well acknowledged by early adopters of this technique. TaTME registry data showed visceral injuries during perineal dissection including five urethral injuries (0.7%), two bladder injuries (0.3%), one vaginal perforation (0.1%), and two rectal tube perforations (0.3%). 30 The systematic review also detected five cases (0.6%) with urethral injury and five cases (0.6%) with bleeding from the pelvic side wall among 794 patients. 33 According to a recent survey of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) consultant members, TaTME training was the top educational need for surgeons who wish to start TaTME. 35

| Lateral pelvic lymph node dissection
The beneficial effect of lateral pelvic lymph node dissection (LLND) had been under debate for a long time until the results of the JCOG0212 trial were published in 2017. 40 Five-year OS, and 5-year local-recurrence-free survival in the mesorectal excision (ME) with LLND and ME-alone groups were 92.6% and 90.2%, and 87.7% and 82.4%, respectively. Local recurrence rates were 7.4% and 12.6% in the ME with LLND and ME-alone groups, respectively (P = .024).
Kanemitsu et al 41 also reported the outcomes from a total of 1191 consecutive patients with lower rectal cancer who underwent TME with LLND. They described that dissection of the internal iliac nodes and obturator nodes yielded similar therapeutic benefits to those expected from dissection of the superior rectal artery nodes. They also showed that the relative risk for local recurrence was 2.0 for patients with unilateral LLND compared with those with bilateral LLND. Based on these results, ME with LLND is still a standard treatment in Japan. It should be noted that patients with lateral lymph nodes (LLN) larger than 10 mm were excluded and that no patient received any preoperative treatments in JCOG0212.
The effect of additional LLND after preoperative treatment is unclear. Ishihara et al 42 reported that the incidence of LLN metastasis was estimated to be 8.1% (18/222) even after preoperative CRT.
Yamaoka et al also reported that LLN metastasis was detected in seven out of 19 patients who underwent preoperative CRT, suggesting preoperative CRT followed by ME alone is not sufficient, especially when LLN involvement is clinically suspicious. 43 Ishihara's group carried out TME + LLND for patients with swollen LLN following preoperative CRT. 42 Akiyoshi's group also carried out LLND with a similar theory and reported 3-year relapse-free survival of 75.1% for patients with LLN metastasis. 44 Currently, RCT to assess the efficacy and safety of LLND after preoperative CRT for rectal cancer patients with suspicious LLN metastases is ongoing in China. 45 Kusters et al reported that the lateral local recurrence rate was significantly higher in patients with LLN larger than 10 mm than in patients with smaller nodes despite the use of preoperative radiation. 46 The optimal cut-off value of LLN size for prediction of metastasis varies among the investigators. Ishibe et al 47 reported that a cut-off value of 10 mm was useful for avoiding unnecessary LLND. Akiyoshi's group reported that the optimal cut-off value before CRT was 8 mm. 44 Yamaoka reported an optimal cut-off value of 6.0 mm, with a sensitivity of 78.5% and a specificity of 82.9%. 43 Before the start of preoperative treatment, accurate estimation of LLN size by MRI is useful.
Although JCOG0212 reported that LLND did not increase male sexual dysfunction, LLND is considered technically challenging. 48 Recently, the safety and feasibility of laparoscopic versus open LLND was shown by a subgroup analysis of a large multicenter cohort study from Japan. 49 They also showed similar oncological outcomes between the groups.
Establishment of criteria to accurately predict LLN status as well as standardization of the technique of LLND is necessary in the future.

| Preoperative therapy
Currently, fluorouracil-based chemoradiotherapy is the golden standard of preoperative therapies for locally advanced rectal cancer. 50 However, the beneficial effect of addition of oxaliplatin to CRT is con- There is increasing interest in a watch-and-wait approach as a management option for patients with rectal cancer who received preoperative therapy. The OnCoRe project, which was a propensityscore matched cohort study, was reported in 2016. 54 In that project, non-regrowth DFS rates for the watch-and-wait and surgery groups were 88% and 78%, respectively (P = .022 by the log-rank test). The systematic review published in 2017 reported that the regrowth rate in the watch-and-wait group was 21.3% and salvage surgery was possible in 93.2% of these patients. 55 Another meta-analysis compared the oncological outcomes of the patients who had watch-andwait after cCR versus those who had radical surgery after cCR or versus patients with pCR after surgery. 56