The optimal length of DRM has not been determined during sphincter-sparing surgery for patients with mid-low rectal cancers, due to the lack of evidence from high-level randomized controlled studies. In this situation, it is challenging to choose a reasonable surgical type (e.g., low anterior resection or APR) for both surgeons and patients. Therefore, the investigation of the effect of the DRM on the oncological results of the low-lying rectal cancer patients is necessary and of important clinical significance. In the current study, patients with positive CRM and/or DRM were excluded in order to avoid interference with the oncological results. Several studies[17, 18] have confirmed that positive CRM was significantly associated with worse clinical outcomes. Patients with microscopically positive DRMs were related to a significantly higher local recurrence rate[3, 19].
The length of the DRM is mainly depended on the tumor location in the rectum. In this study, the mean distance from the anal verge in the DRM ≤ 1 cm group was shorter than that in the DRM > 1 cm group, similar to previous studies[13, 20, 21]. Meanwhile, we found that the proportion of patients with T1 and T2 stages in the DRM ≤ 1 cm group was higher than that in the control group. Similarly, the proportion of the patients with stage Ⅰ and Ⅱ in the DRM ≤ 1 cm group was higher than that in the DRM > 1 cm group. This condition is mainly caused by case selection. Compared to low-lying rectal cancer patients with advanced T/TNM stage, patients with earlier stage are more likely to be received sphincter-preserving resection rather than APR.
Overall, there were no significant differences in the 5-year LR rate, 5-year DFS, and 5-year OS between the two groups in this study. Similarly, A systemic review of 5574 rectal cancer patients conducted by Bujko et al. [22] was to evaluate whether a DRM of < 1 cm jeopardizes oncologic safety. They concluded that a DRM of < 1 cm did not compromise oncologic outcomes. Dong Woo Kang et al.[21] reported that the 5-year LR rate was 8.8% in the DRM ≤ 1 cm group and 8.5% in the DRM > 1 cm group (p = 0.630). The 5-year DFS rate was 75.1 and 76.3% (p = 0.895), and the 5-year OS rate was 82.6 and 85.9% (p = 0.401), respectively. In the study, about 41.4% of enrolled patients were treated by NCRT according to risk factors, such as cT4, positive CRM.
Many previous studies[13–16, 19, 20, 23] attempted to define the narrowest sufficient DRM ( 5 mm, 8 mm, 1 cm, and 2 cm) in patients with sphincter-preserving surgery. However, most of these studies, the analysis of the impact of DRM on survival results was not well stratified by NCRT.
A subgroup analysis of this study showed that there were no significant differences in the 5-year LR and 5-year DFS between the two groups in 44 patients who received NCRT. In agreement with our result, Philipp et al. analyzed 88 patients with mid-low rectal cancer receiving NCRT. They found that the 5-year LR rate was 6.7% in patients with DRM < 1 cm and 5.5% in patients with DRM ≧ 1cm[13]. Preoperative chemotherapy may increase the rate of sphincter-preserving surgery due to the regression of primary tumors[24, 25]. It was reported that neoadjuvant chemoradiation of tumors was associated with shorter distal spread compared to tumors without preoperative radiation[26, 27].
In addition, many previous studies showed that distal intramural spread greater than 1 cm was only in 0–5% of patients[26, 28, 29]. However, Akihiro Kondo et al.[16] analyzed 71 patients with low rectal carcinoma who received preoperative chemotherapy. They found that 42 (59%) patients had distal spread. Distal spreads of 10–19 mm, and ≧ 2 cm were observed in 11 (15%), and 4 (6%) patients, respectively. Besides, they revealed that the presence of different therapeutic effect between the mucosal and deeper layers and poorly differentiated adenocarcinoma were independent risk factors for DRM ≧ 1 cm after preoperative chemotherapy. Thus, these findings suggest that for carefully selected patients with neoadjuvant chemoradiotherapy, a subcentimeter DRM is acceptable and not associated with worse oncologic results. It should be noted that for patients with high-risk factors who underwent preoperative chemotherapy, a DRM of 1 cm may not be sufficient.
By subgroup analysis in the present study, a DRM of ≤ 1 cm did not compromise the oncologic outcomes of patients who received TME surgery alone. The introduction and application of TME principle for advanced rectal cancer have significantly reduced local recurrence and improved a safe DRM[7, 30, 31]. A study including 152 mid-low rectal cancer patients with TME surgery alone reported that there were no significant differences in 10-year recurrence rates between the DRM ≤ 1 cm group and the DRM > 1 cm group (0.0 vs. 3.6%, p = 0.27). The authors believed that sphincter-saving TME with a subcentimeter DRM was a preferable option to preserve anal function without compromising oncological safety. Although patients were not treated by NCRT, postoperative adjuvant chemotherapy and/or radiotherapy may compensate for the negative impact of near margin on survival.
The present study has several drawbacks. First, some statistical bias is inevitable due to the retrospective nature of the research design. Prospective cohort studies will be conducted to reduce such errors. Second, although the total sample size is large, the number of patients with a DRM ≤ 1 cm group is small. Third, The proportion of patients receiving neoadjuvant therapy was low, and adjuvant therapy was not uniform, which may affect oncologic results. In addition, not all specimens in this study were pinned. So, the length of DRM may be affected by different measurement methods. Tissue shrinkage of about 30% in unpinned specimens was caused by formalin fixation, and no significant difference was observed in the DRM length of formalin-fixed specimens if they had been pinned[32, 33].