Lateral Lymph Node Dissection After Neoadjuvant Chemo-radiation in Advanced Low Rectal Cancer

Overview

Lateral lymph nodes (LLD) metastasis is a major cause of local recurrence for advanced rectal cancer. As for the treatment strategies on LLN metastasis, there are huge controversies on whether lateral pelvic lymph nodes dissection (LLND) after neoadjuvant chemo-radiotherapy (nCRT) between Western and Eastern countries. Retrospective cohort evidences indicate that LLND following total mesorectal excision (TME) will bring benefit from cT3-4 rectal cancer, not regular predictive LLND, which will bring more side effects on the contrary. Existing reports tend to recommend LLND for specific individual with suspicious LLN metastasis. Moreover, there is a blank strict prospective randomized control study on the comparison of LLND+TME and LLND after nCRT. Therefore, our trial will compare the efficacy and safety of the two strategies for mid/low rectal cancer with suspicious LLN metastasis. The risk factors (such as radiologic factors, pathologic factors, and serum protein) to predict local recurrence and overall survival will be further investigated.

Recently, the incidence and mortality of colorectal cancer have increased, leading the second prevalence after lung cancer. Local recurrence of mid/low rectal cancer is not only the poor prognostic factor but also the threat of terrible quality of life. Although universal usage of neoadjuvant chemo-radiotherapy (nCRT) and total mesorectal excision (TME) have decreased local recurrence to 5%-10%, the ratio of local recurrence has occupied almost 30% of total metastasis and recurrence incidences, which limited the therapeutic effect of rectal cancer. Increasing evidences have demonstrated lateral pelvic lymph nodes (LLN) metastasis as one of the prominent causes of local recurrence, accompanied with 10%-25% advanced rectal cancer. Published researches also reminder us preoperative LLN involvement may lead to high local recurrence and poor overall survival. As for the treatment strategies on LLN metastasis, there are huge controversies on whether lateral pelvic lymph nodes dissection (LLND) or LLND+TME after nCRT: Eastern countries especially Japan favors LLND following TME with the reasons: 1) the incidence of LLN metastasis reaches as high as 10%-25% and 27% of rectal patients who undergo TME solely (without LLND) will develop into local recurrence. And the predictive pelvic recurrence rate will decrease 50%; corresponding 5-year overall survival will increase 8%-9%. 2) efficacy of LLND equals to resection of "local lymph nodes metastases". A large cohort of 11567 cases from Japan demonstrates resection of iliac lymph nodes metastasis does not show any difference from TME of cTxN2aM0 and resection of obturator and external iliac lymph nodes favors that of liver metastasis. 3) Japanese Guidelines for treatment of colorectal in 2014 also recommends mid/low II/III rectal cancer under peritoneal reflex undergo regular TME+LLND. On the contrary, western countries favor sole TME after nCRT for LLN metastasis, holding that: 1) rate of lymph nodes metastasis is relatively low and LLN metastasis is regarded as systemic metastasis. 2) LLND experiences longer operative time, higher postoperative complications, and poor quality of life. 3) American NCCN and European ESMO guidelines recommend single TME for rectal cancer, if necessary, LLDN is added when LLN is indeed metastasis. However, there is a blank strict prospective randomized control study on the comparison of nCRT and LLND. Present existing retrospective cohort mainly focus on all the mid/low advanced cancer, not the specific individual of suspicious LLN metastasis. In fact, the results almost indicate no differences on local recurrence and overall survival, except for less operation time, blood loss, and perioperative complications in LLND. Although the latest researches start to report their preliminary outcomes, the patients sample sizes are small and they achieve varied recurrence and overall survival. In conclusion, the treatment strategy for colorectal cancer has focused on individual and precision. Massive of retrospective reports have indicated that rectal cancer patients with LLN metastasis will benefit from LLND, however, there is hot controversy on the treatment of whether TME+LLND or TME+nCRT for specific rectal patients with suspicious LLN metastasis. Therefore, our trial will compare the efficacy and safety of the two strategies for mid/low rectal cancer with suspicious LLN metastasis. The risk factors (such as radiologic factors, pathologic factors, and serum protein) to predict local recurrence and overall survival will be further investigated.