The influence of neoadjuvant chemoradiotherapy combined with lateral lymph nodes dissection or not on the local recurrence of low to intermediate-stage II/III rectal cancer

Background: Currently, the treatment options for stage II/III rectal cancer with preoperative lateral lymph nodes (LLN) enlargement are highly controversial between East and West, and the indications for diagnosing suspiciously positive enlarged LLN are inconsistent both nationally and internationally. Oriental scholars (especially Japanese) consider the LLN as a regional disease, they consider that prophylactic lateral lymph nodes dissection (LLND), regardless of whether the LLN is enlarged or not, is considered necessary if the tumor is found beneath the peritoneal reflex and invades the muscle layer. Western scholars regard LLN as distant metastases, recommending neoadjuvant chemoradiotherapy (nCRT) in conjunction with total rectal mesenteric resection (TME). In recent years, it has been found that neither of the two standard treatment regimens, East and West, significantly improved local control of tumors in patients with LLN enlargement. In contrast, nCRT combined with LLND significantly lowers the local recurrence (LR) rate. It has also been suggested that combination therapy regimens do not improve patient prognosis but increase treatment-related complications. Therefore, the suitable therapeutic option for rectal cancer with an enlarged LLN needs to be further explored.Aim: Exploring appropriate treatment options for low to intermediate-stage II/III rectal cancer with LLN enlargement, as well as risk variables that may affect the LR in these patients with LLN enlarged.Methods and patients: In this research, we retrospectively analyzed 110 patients with locally advanced mid-low (low boundary of tumor is no more than 10 cm from the anus) rectal cancer who were treated at Harbin Medical University Cancer Hospital arranged from 2017.1 to 2020.6. These patients had received nCRT and TME, and their initial rectal nuclear magnetic resonance imaging (MRI) revealed an enlarged LLN (short axis of LLN, SA >= 5 mm). Of these, 40 patients underwent LLND, thus, 110 patients were grouped into two groups: nCRT+TME (LLND-, n = 70) and nCRT+TME + LLND (LLND+, n = 40), and their 3 years prognoses were compared.Results: After a median follow-up of 49.0 months, the 3-year LR rate of the LLND- group was notably greater than the LLND+ group (22.8% vs. 7.5%, p = 0.04). However, there was no noteworthy difference in the 3-year progression-free survival (PFS, 70.5% vs. 77.5%, p > 0.05) rate or distant metastasis (DM) rate (20.0% vs. 17.5%, p > 0.05). Additionally, the LLND+ group experienced significantly more postoperative complications than the LLND- group (15.0% vs. 4.2%, p = 0.05). Subgroups analysis for the LLND- group revealed that patients with LLN short axis regression (Delta SA) > 35.9% after nCRT had significantly lower 3-year LR rate than patients with Delta SA <= 35.9% (9.1% vs. 35.1%, p = 0.01). Patients in the LLND- group with Delta SA > 35.9%, however, had comparable 3-year LR rate and DM rates to those in the LLND+ group.Conclusion: LLN is an independent indicator for prognosis among people with low to intermediate-stage II/III malignant rectal tumors. Patients with poor SA regression (Delta SA <= 35.9%) after nCRT have a greater risk of positive LLN and a more substantial LR, and nCRT combined with LLND reduced the LR rate significantly, but considerably prolonged operative time, surgical bleeding, and postoperative complications. Patients with better SA regression (Delta SA > 35.9%), however, have a lower possibility of LR and might not need LLN clearance, in these cases, nCRT+TME is advised.