AIM: To evaluate the 5-year survival after laparoscopic surgery vs open surgery for stages II and III rectal cancer.

METHODS: This study enrolled 406 consecutive patients who underwent curative resection for stages II and III rectal cancer between January 2000 and December 2009 [laparoscopic rectal resection (LRR), n = 152; open rectal resection (ORR), n = 254]. Clinical characteristics, operative outcomes, pathological outcomes, postoperative recovery, and 5-year survival outcomes were compared between the two groups.

RESULTS: Most of the clinical characteristics were similar except age (59 years vs 55 years, P = 0.033) between the LRR group and ORR group. The proportion of anterior resection was higher in the LRR group than that in the ORR group (81.6% vs 66.1%, P = 0.001). The LRR group had less estimated blood loss (50 mL vs 200 mL, P < 0.001) and a lower rate of blood transfusion (4.6% vs 11.8%, P = 0.019) compared to the ORR group. The pathological outcomes of the two groups were comparable. The LRR group was associated with faster recovery of bowel function (2.8 d vs 3.7 d, P < 0.001) and shorter postoperative hospital stay (11.7 d vs 13.7 d, P < 0.001). The median follow-up time was 63 mo in the LRR group and 65 mo in the ORR group. As for the survival outcomes, the 5-year local recurrence rate (16.0% vs 16.4%, P = 0.753), 5-year disease-free survival (DFS) rate (63.0% vs 63.1%, P = 0.589), and 5-year overall survival (OS) rate (68.1% vs 63.5%, P = 0.682) were comparable between the LRR group and the ORR group. Stage by stage, there were also no statistical differences between the LRR group and the ORR group in terms of the 5-year local recurrence rate (stage II: 6.3% vs 8.7%, P = 0.623; stage III: 26.4% vs 23.2%, P = 0.747), 5-year DFS rate (stage II: 77.5% vs 77.6%, P = 0.462; stage III: 46.5% vs 50.9%, P = 0.738), and 5-year OS rate (stage II: 81.4% vs 74.3%, P = 0.242; stage III: 53.9% vs 54.1%, P = 0.459).

CONCLUSION: LRR for stages II and III rectal cancer can yield comparable long-term survival while achieving short-term benefits compared to open surgery.

Laparoscopic rectal resection (LRR) is regarded as a technically demanding approach and many colorectal surgeons attempt LRR for early-stage rectal cancer or tumors in small size in their initial stages[1,2]. With the improvement in surgical technique and instruments, experienced surgeons have attempted to apply LRR for locally advanced rectal cancer. However, long-term oncologic outcomes of laparoscopic surgery for locally advanced rectal cancer remains controversial. Among the published trials comparing the long-term oncologic outcomes of rectal cancer between LRR and open rectal resection (ORR) groups[3-11], there were rare trials involving subgroup comparison of stage II or III rectal cancer[9]. The 5-year oncologic outcomes of the trial for stage II or III rectal cancer is not persuasive enough for the limited cases[9]. There were retrospective studies providing different long-term oncologic outcomes between laparoscopic and open surgery for stages II and III rectal cancer[12-18]. LRR for rectal cancer has been widely performed by Chinese colorectal surgeons. However, few studies evaluated long-term oncologic outcomes of LRR for stage II or III rectal cancer[12]. The present study was conducted to evaluate the long-term oncologic outcomes of LRR for stages II and III rectal cancer.

Four hundred and sixty-two consecutive stages II and III rectal cancer patients who underwent LRR or ORR from January 2003 to December 2009 were extracted from the clinical colorectal database of Department of General Surgery of Nanfang Hospital, Southern Medical University, which is one of the members of the Southern Chinese Laparoscopic Colorectal Surgery Study (SCLASS) group[19]. After excluding 44 patients who underwent emergency resection and 12 patients with recurrent disease, 406 cases were finally included in the present study, with 152 undergoing LRR and 254 undergoing ORR.

The tumors were subdivided into three types according to the distances between their distal borders and the anal verge (upper rectal cancer, 10-15 cm; middle rectal cancer, 5-10 cm; and lower rectal cancer, < 5 cm). Patients chose the surgical approach of LRR or ORR based on an understanding of the risks and benefits inherent to laparoscopic and open resection after having received an extensive explanation without any pressure from the surgeon. LRR and ORR were performed by three colorectal surgeons who were experts in both laparoscopic and open procedures.

Before operation, all patients underwent colonoscopy plus biopsy, pelvic magnetic resonance imaging (MRI) or abdominal computed tomography (CT). A liquid diet was started after the first flatus had been passed. Patients were discharged if they were analgesia-free, afebrile and can tolerate food for 24 h, without major complications. Patients with high risk factors were recommended to receive postoperative adjuvant chemotherapy with 5-fluorouracil-based regimens. The last follow-up was December 2013.

LRR was reported a technically demanding procedure for the difficulties in pelvic exposure and TME with the autonomic nerves preserved[12,20-22]. The application of LRR in early rectal cancer was usually accepted by laparoscopic surgeons[2,13]. Although more and more locally advanced rectal cancer cases have undergone LRR by experienced surgeons, there was still skepticism on the application of LRR for locally advanced rectal cancer for the limited data on the long-term oncologic outcomes. To date, the multi-center randomized controlled trial (RCT) of CLASSICC has provided the highest level of evidence on equivalent 3-year and 5-year local recurrence, DFS and OS rates of LRR compared to ORR[3,10]. However, there was no subgroup analysis of locally advanced rectal cancer in this trial and the maturity of the technique of laparoscopy had been questioned for a relatively high conversion rate and morbidity[23-25].

This study showed that, compared to ORR, LRR for locally advanced rectal cancer had less estimated blood loss, faster bowel function recovery, and, most importantly, similar 5-year local recurrence, DFS, and OS rates. The Cox regression indicated that surgical approach was not the factor that significantly impacted on 5-year local recurrence, DFS, and OS rates.

Studies demonstrated that circumferential resection margin (CRM) status was highly associated with long-term survival[26-28]. Pathological involvement of the CRM after rectal cancer surgery is a well-established prognostic indicator[29]. Clear CRMs are of great importance because the risk of local recurrence increases three to four times when these margins are invaded by tumor cells[30]. Changes in awareness of the requirements for pathologic evaluation of rectal cancer specimens began in 2007. However, the SCLASS database collected patient clinical data prior to 2009. Consequently, data on CRMs were not recorded in the current SCLASS database for the sake of consistency, which is one limitation of our study. Nevertheless, our results showed that laparoscopic approach did not have an adverse effect on local recurrence or DFS, which may be considered putative proxies for CRM. Wang et al[31] reported CRM involvement in patients with rectal cancer of approximately 1.9% at a leading single institution in China. This may indirectly reflect the status of CRM involvement in China. Additionally, during the last 20 years, the treatment of rectal cancer has changed dramatically. The reinforcement of TME by our understanding of the mesorectum and CRM has led to fewer positive margins and consequently fewer local recurrences[32].

The use of neoadjuvant therapy has only been highly recommended by NCCN guidelines in recent years, while the clinical data of the present study began from January 2003. This discrepancy contributed to the relatively low rate of patients who received neoadjuvant therapy in the present study. Only < 10% patients in our study had received treatment for rectal cancer with neoadjuvant therapy in both groups. Though a low rate of neoadjuvant therapy and adjuvant therapy, the proportions of them between the LRR group and ORR group were comparable, which helped result in similar long-term oncological outcomes between the two groups.

Although one RCT and two non-randomized studies have demonstrated that laparoscopic approach was an independent predictor of improved survival after colorectal surgery[14,33,34], laparoscopic approach was not associated with differences in survival or recurrence in our study. One of the reasons for the difference in our findings may be that > 50% of patients in the abovementioned studies were colon cancer patients. Therefore, their findings may not be applicable to rectal cancer. In our study, patient survival following LRR for rectal cancer was similar to survival following ORR, with acceptable complications and earlier recovery. The present study showed less estimated blood loss, a lower rate of blood transfusion, and quicker postoperative recovery. These non-inferior parameters relevant to surgical stress response and postoperative immune function of the LRR group may help result in non-inferior long-term oncological outcomes of the LRR group in the present study[35,36]. Together, the data suggest that it is not necessary to prove a survival benefit of LRR over ORR to justify its use in the treatment of rectal cancer.

The retrospective design was one main limitation of the present study and selective biases were unavoidable in the present study, such as the average age of the patients and the proportion of surgical procedure of AR and APR, though they had not significantly different impact on the long-term oncologic outcomes by Cox regression mode multivariate analysis. Furthermore, the rates of noeadjuvant and adjuvant treatment were low and the specimen lacked CRM status. Despite these limitations, this cohort study was specially created to compare local recurrence, DFS and OS rates between LRR and ORR for locally advanced rectal cancer in a Chinese population.