ELAPE has been performed in patients with low rectal cancer in recent years and has resulted in superior oncologic outcomes compared with APE, but controversy exists regarding the long-term survival of this technique13,16. In the current study long-term outcomes of patients undergoing ELAPE and APE were evaluated, and we showed that ELAPE improved survival of patients with low rectal cancer when compared with APE, especially for patients with pT3 tumors, positive lymph nodes or those without neoadjuvant chemoradiotherapy.
Despite a wider range of resection, the lymph nodes harvested in the ELAPE group were significantly less in number than the APE group. Although more tissue is removed with ELAPE, the number of lymph nodes dissected is not necessarily increased. Alternatively, the effect of a higher proportion of patients receiving neoadjuvant chemoradiotherapy in the ELAPE group. We found that the number of lymph nodes harvested in the patients who received neoadjuvant chemoradiotherapy was significantly less than patients who did not in the ELAPE group (11 versus 15, P < 0.001). A nationwide study showed that fewer nodes were examined in patients who underwent preoperative chemoradiotherapy compared to patients who did not17. Furthermore, although it has been proposed that increasing the number of lymph nodes harvested might increase the probability of recovering positive lymph nodes18, the number of patients with positive nodes was similar in both groups in the current study. Persiani et al.19 was also of the opinion that a low number of lymph nodes harvested during surgery after neoadjuvant chemoradiotherapy does not represent inadequate resection or understaging, rather an increased sensitivity to the treatment.
In theory, ELAPE has the potential to reduce local recurrences and improve survival in low rectal cancer patients with more peritumoral tissue removed. The long-term survival of low rectal cancer patients undergoing ELAPE and APE has been a matter of debate in recent years13,16,20. Klein et al.13 reported that there is no evidence indicating that ELAPE yields better survival compared to APE. This population, however, had more early-stage tumors (46 per cent considered to be pT1−2), which might explain why no statistical difference in survival was detected between the two operation types. Shen et al.6 has proposed a different view. Specifically, a multicenter study revealed that ELAPE is associated with longer survival than APE (median OS, 41.5 versus 29.8 months, P = 0.028; median DFS: 38.5 versus 29.3 months, P = 0.027; local recurrence rate: 3.80 per cent versus 11.5 per cent, P = 0.027). In the current study, we showed that ELAPE improved long-term PFS and LRFS for all patients with low rectal cancer compared to APE, which was consistent with the results of Shen et al.6. Even though a significant OS was obtained, ELAPE had the added benefit of reducing local recurrences and distant metastases, which facilitates decision-making in selecting the optimal operation type for patients with low rectal cancer.
Further stratified analyses showed patients with pT3 tumors had better survival outcomes in the ELAPE group than the APE group with comparable neoadjuvant chemoradiotherapy rate [34.5 per cent (10 of 29) versus 21.7 per cent (5 of 23), P = 0.314]. Due to insufficient resection range at the surgical waist, APE was associated with a higher risk for positive CRM, which can easily lead to local recurrences. Compared to APE, more peritumoral tissues are removed in patients who undergo ELAPE to avoid the formation of a waist at the anorectal junction, thus reducing the positive CRM rate and improving survival outcomes21. In the current study, although the difference in positive CRM rates between the two groups was not significant for all patients, for pT3, the positive CRM rate for pT3 in the ELAPE group was significantly lower compared to the APE group [0 versus 13 per cent (3 of 23), P = 0.045]. In contrast, complete removal of the mesorectum during the ELAPE procedure reduces the perforation rate during the operation and the incidence of recurrences and metastases22. In addition, with less direct manipulation and squeezing of the tumor during ELAPE, the likelihood of distant metastasis caused by the cancer cells entering the blood is reduced. The importance of resection along the lateral fascial plane of the external anal sphincter-levator muscle is emphasized in the ELAPE procedure in compliance with the precise principle of radical removal23. Based on our analysis, ELAPE is more suitable for patients with pT3 rectal cancer.
For patients with positive lymph nodes, ELAPE resulted in an incremental survival benefit in the current study with a higher proportion of patients receiving neoadjuvant chemoradiotherapy. For cases that tumor was difficult to remove, neoadjuvant chemoradiotherapy can downstage the tumor to increase the probability of resection24,25. Even though neoadjuvant chemoradiotherapy is essential in the treatment of advanced rectal cancer, we suggest that the ELAPE might be a crucial method by which to promote survival, as confirmed by multivariate analysis. In the current study patients had a significantly higher 5-year PFS in the ELAPE group than the APE group with or without preoperative neoadjuvant chemoradiotherapy. Seshadri et al.21 also reported that ELAPE resulted in better CRM and IOP outcomes when compared with APE, even after neoadjuvant chemoradiotherapy, but concluded that the operation type still plays an important role in long-term survival. Compared with APE, ELAPE removed more tissue to achieve total mesorectal excision, which might have a positive effect on the prognosis of low rectal cancer patients26.
ELAPE has advantages in treating lower rectal cancer compared to APE, but this superiority wasn’t reflected in pT0−2 and pT4 patients in the current study. For pT1−2 tumors, in which cancer cells shallowly infiltrate the intestinal wall, ELAPE might not further improve the prognosis with more tissue removed. For pT4 tumors, although our study with its relatively small sample size did not demonstrate significant differences in survival between two groups, we think we cannot ignore the effect of location of the tumor and invasion depth on local recurrrence. We showed that in pT4 tumors the positive CRMs were mostly associated the resection margin of the anterior wall. We speculate that located in the anterior wall of the rectum, pT4 tumors might invade the prostate or vaginal wall which is associated with local recurrence after resection28,29. Nevertheless, well-designed prospective randomized clinical trials are needed to improve the prognosis of patients with pT4 low rectal malignant tumors.
This study had the following limitations. First, this was a retrospective study and selection bias was therefore inevitable. The ELAPE group was more likely to receive preoperative neoadjuvant chemoradiotherapy in this study. Then, as indications for anal preservation in low rectal cancer surgery have relaxed, the number of ELAPE and APE cases have correspondingly declined. The sample size of some subgroups was small, and that definitely affected the precision of the estimations in this study. The relatively small number of patients could limit the interpretation of the results. Finally, the postoperative local recurrence rate of this study was relatively high [21.9 per cent (25 of 114)], especially in the APE group [30.4 per cent (14 of 46)]. We considered that the inclusion of advanced tumors suggested by preoperative impact studies and long follow-up time may also account for it, and the small sample size is another reason. Some indicators such as incidence of intraoperative perforation, quality of mesorectal excision were missing.