Previous studies from Eastern and Western countries have reported that, for patients with preoperative lateral lymph node enlargement, nCRT without LPND results in a high rate of lateral pelvic recurrence after surgery[20–22]. Therefore, we conducted a retrospective study to explore the surgical indications for LPND after nCRT for patients with suspected LPNM before surgery and to investigate the oncological outcomes and prognostic values for rectal cancer patients treated with TME+LPND following nCRT. Our results found that a post-nCRT LPN size ≥7 mm and lymphatic invasion were independent risk factors for pathological LPNM after nCRT in rectal cancer patients with suspected LPNM before surgery. In addition, even if TME+LPND was performed after nCRT, patients with pathological LPNM still showed a higher overall recurrence rate (60.0% vs 27.6%, P=0.018) compared to those without pathological LPNM. Multivariate regression analysis identified that LPNM was an independent risk factor not only for OS (HR: 3.82; 95% CI, 1.19-12.25; P=0.024) but also for DFS (HR: 2.50; 95% CI, 1.05-5.92; P=0.038).
In previous studies, the incidence of LPNM for patients with stage II-III rectal cancer was demonstrated to be 10%-20%[1–2]. All the patients included in the present study were suspected of having LPNM by preoperative MRI evaluation, and the rate of pathological LPNM was only 20.5%, which is related to the relatively loose imaging diagnostic criteria of LPNM. The present study showed that pathological LPNM was significantly affected by post-nCRT size and lymphatic invasion. The selection of the optimal cut-off value of post-nCRT LPN size remains controversial, with the most common cut-off values currently being 5 mm[1, 23, 24] and 7 mm[14, 16]. Chen et al. reported that persistent LPN size ≥7 mm on post-nCRT MRI was significantly associated with LPNM after nCRT (OR = 7.539, 95% CI: 1.49-38.21; P = 0.015)[16]. Furthermore, Inoue et al., however, thought that 7 mm could be a more appropriate cut-off [14]. In our study, we set 7 mm as the cut-off for post-nCRT LPN size. As a result, 93.3% (14/15) and 15.5% (9/58) of patients with LPN ≥7 mm were found in the positive and negative LPN groups, respectively. Multivariate logistic regression analysis demonstrated that a post-nCRT LPN size ≥7 mm (OR: 55.43; 95% CI, 4.24-724.42; P=0.002) and lymphatic invasion (OR: 11.81; 95% CI, 1.75-79.59; P=0.011) were independent risk factors for pathological LPNM, and these results were consistent with the abovementioned results.
A meta-analysis of 18 studies involving 6133 patients suggested that additional LPND results in greater postoperative morbidity, urinary dysfunction, and sexual dysfunction, without improving recurrence and long-term survival[25]. Moreover, it has been reported that patients with pathological LPNM, even after TME+LPND, still have a higher local recurrence rate and a worse prognosis than patients without pathological LPNM[5,26−29]. However, the role of nCRT in LPNM has become clearer in recent years, and this study investigated the oncology outcomes of TME+LPND after nCRT for patients with LPNM. Our study demonstrated that patients with pathological LPNM who received TME+LPND after nCRT still showed a higher overall recurrence rate after surgery (60.0% vs 27.6, P=0.018). Similarly, a retrospective study involving 899 patients at a high-volume cancer centre in Japan conducted by Wang et al. revealed that, even with LPND, patients with pathological LPNM still showed an elevated risk of local recurrence (30.0% vs 10.0, P=0.025)[5]. Meanwhile, the present study revealed that the 3-year OS (46.3% vs 83.7%, P=0.006) and DFS (28.6% vs 67.2%, P=0.009) of patients with LPNM were significantly worse than those without LPNM, and the multivariate regression analysis identified that LPNM was an independent risk factor not only for OS (HR: 3.82; 95% CI, 1.19-12.25; P=0.024) but also for DFS (HR: 2.50; 95% CI, 1.05-5.92; P=0.038) through multivariate regression analysis. A retrospective study involving 149 rectal patients conducted by Sato et al. showed that the 5-year OS rate was significantly worse in patients with LPNM (36.2% vs 69.8%, P=0.0004), and multivariate Cox regression analysis for factors affecting the prognosis showed that LLN metastases had an independent predictive value in determining prognosis (HR: 2.41; 95% CI, 1.37-4.26; P=0.002)[29], which is basically consistent with our results. Considering the greater postoperative morbidity, urinary dysfunction, and sexual dysfunction associated with LPND, we suggest that it is necessary to explore which types of patients with pathological LPNM can benefit from TME+LPND after nCRT.
This study was associated with several limitations, including the retrospective nature and small sample size of only 73 patients included. Second, the study period was from 2015 to 2021, and the adjuvant chemotherapy regimens adopted by the included patients were inconsistent, which may cause some interference with the prognosis. Moreover, this study only verified the oncology outcomes of LPND for patients with clinically suspected LPNM. It is impossible to compare the local control effect of prophylactic LPND in stage II-III patients with middle-low rectal cancer due to the nonroutine practice of prophylactic LPND in our institution. Finally, the number of patients with pathological LPNM in our analysis was too small to perform an appropriate multivariate analysis to identify which types of patients with LPNM may achieve a survival benefit from LPND. Therefore, randomized controlled studies with larger numbers of patients are needed to further verify our findings.