Our study suggests that the histological effect of rectal lesions by CRT does not support the omission of LLND. And the minor axis of the lateral lymph node and PLR are risk factors for recurrence of the lateral lymph node.
The American Society of Colon and Rectal Surgeons (ASCRS) strongly recommends not performing LLND in the absence of swollen lateral lymph nodes. However, it does not mention appropriate treatment strategy for patients with swollen lateral lymph nodes. (18)
Fujita et al. reported that 5-year relapse-free survival rate in the TME + LLND group wan not improved compared with TME group. Morevoer, lateral pelvis recurrence was significantly high in TME group and, recurrence of lateral lymph nodes has been reported to be the leading cause of pelvic recurrence in the absence of LLND after CRT, (19, 20) and the usefulness of LLND has also been recognized in Western countries.
Hazen et al. reviewed the treatment of lateral lymph nodes in rectal cancer and state that they will change towards selective LLND in the future. (21) Therefore, it is important to develop predictors of lateral lymph node metastasis.
Regarding lymph node size and cancer recurrence, previous studies investigated LLND indication by lymph node size, and specific criteria have not yet been established. Kawai et al. reported that lateral lymph node recurrence rate was 1.6% in post-CRT + TME and TME + LLND was performed on patients with 8 mm LLN before surgery, and the positive rate for lateral lymph node metastasis was 52.4%. And the estimated incidence of LLN metastases after nCRT was 9.3%. (10)
They also reported that some of patients who underwent LLND did not develop local cancer recurrence through post-operative observation and assessment of lymph node size had 1-mm interobserver error, and there is a limit to the evaluation based on the lymph node size alone. (10) In the currency study, patients with pre-CRT lymph node minor-axis diameter less than 11.6 mm and post-CRT diameter less than 5.5 mm did not develop lateral lymph node recurrence. While the results in the current study did not show significant difference compared to previous studies, only 5 patients developed lateral lymph node recurrence. Further studies with additional cases are necessary.
Predictive factors of therapeutic effect, histological effect, and lateral lymph node recurrence
Previous studies showed that patients with good histological effect had favorable outcome. (22,23) However, some patients with TRG 1 exhibited lymph node metastasis.
It has been reported that 4.6% of patients with TRG1 were positive for lymph nodes in the mesorectum, and that the lymph nodes in the mesorectum were associated with the TRG of the tumor itself. (24,25) However, its association with lateral lymph nodes has not been investigated. Although it is unclear why there is a difference in the control of lymph nodes in the irradiation range, our study found no association between lateral lymph node recurrence, TRG, and tumor shrinkage.
Inflammation is associated with tumor formation, and various predictive factors are investigated. Previous studies showed that CEA, NLR, and PLR were related to the histological effect. (12–15) Therefore, in the present study, we assessed the relations between each factor and the lateral lymph node recurrence, and found significant relations between pre- and post-CRT PLRs and lateral lymph node recurrence. Lee et al. reported PLR had a close relation with pathological complete response (pCR). (14) Current results and previous report suggest that PLR is useful not only for assessment of histological effect, but also it can be used as a predictive factor of lateral lymph node recurrence. While PLR can be easily calculated from standard blood sampling, there is no consensus regarding COV.
We are aware of several limitations in the current study, which include a single institutional study and small sample size. In the current study, positive cases were defined as lateral lymph node recurrence without local recurrence, however, true lateral lymph node recurrence might not be captured. Despite these study limitations, the current study is the first study which assessed lateral lymph node recurrence by various factors not limited to the lymph node size. Further studies with additional cases are necessary.