Long-term follow-up of the randomized trial of mesorectal excision with or without lateral lymph node dissection in rectal cancer (JCOG0212)

Abstract

Background Japan Clinical Oncology Group (JCOG) 0212 (http://clinicaltrials.gov NCT00190541) was a non‐inferiority phase III trial of patients with clinical stage II–III rectal cancer without lateral pelvic lymph node enlargement. The trial compared mesorectal excision (ME) with ME and lateral lymph node dissection (LLND), with a primary endpoint of recurrence‐free survival (RFS). The planned primary analysis at 5 years failed to confirm the non‐inferiority of ME alone compared with ME and LLND. The present study aimed to compare ME alone and ME with LLND using long‐term follow‐up data from JCOG0212. Methods Patients with clinical stage II–III rectal cancer below the peritoneal reflection and no lateral pelvic lymph node enlargement were included in this study. After surgeons confirmed R0 resection by ME, patients were randomized to receive ME alone or ME with LLND. The primary endpoint was RFS. Results A total of 701 patients from 33 institutions were assigned to ME with LLND (351) or ME alone (350) between June 2003 and August 2010. The 7‐year RFS rate was 71.1 per cent for ME with LLND and 70·7 per cent for ME alone (hazard ratio (HR) 1·09, 95 per cent c.i. 0·84 to 1·42; non‐inferiority P = 0·064). Subgroup analysis showed improved RFS among patients with clinical stage III disease who underwent ME with LLND compared with ME alone (HR 1·49, 1·02 to 2·17). Conclusion Long‐term follow‐up data did not support the non‐inferiority of ME alone compared with ME and LLND. ME with LLND is recommended for patients with clinical stage III disease, whereas LLND could be omitted in those with clinical stage II tumours.

Pelvic local recurrence as first relapse predicts prognosis for clinical stage II/III lower rectal cancer: A clinicopathological investigation

“…ii) Preoperative chemoradiation and PBLND are conducted to lower the rate of recurrence and improve survival but, although these preoperative treatments significantly lower local recurrence rate, there is little evidence that they improve survival rate. These two reasons do not seem to add up at present (4)(5)(6)(7)(8)(9)(10)(11). An alternative approach could be to control fatal hematogenous metastasis in the lung and liver, which may be more beneficial than reducing local recurrence in extending progression-free and overall survival rates (3,18,19).…”

“…In 2017, the final results of the JCOG0212 study, a randomized, multi-center study of PBLND, were announced. Statistical non-inferiority was not demonstrated in a longitudinal analysis of total mesorectal excision (TME) with or without PBLND, supporting the benefits of conventional PBLND (10,11). However, although local recurrence rate was lower with PBLND, no differences were observed between 5-year relapse-free survival (5Y-RFS) or 5-year overall survival (5Y-OS), or the equivalent 10-year rates, in groups treated with or without PBLND.…”

“…In addition, the circumferential resection margin, anal margin and scattering of tumor cells due to perforation during rectal surgery are reported to influence pelvic local recurrence (3). To improve the survival rate by reducing local recurrence, integrated approaches for advanced rectal cancer, such as preoperative chemoradiation therapy and intrapelvic prophylactic bilateral lymph node dissection (PBLND) have been conducted (4)(5)(6)(7)(8)(9)(10)(11). Specifically, the Japanese Society for Cancer of the Colon and Rectum guidelines 2019 for the treatment of colorectal cancer (JSCCR guidelines 2019) (2) state that evidence is limited for preoperative chemoradiation improving survival rate, although it significantly reduces pelvic local recurrence.…”

Author response to: Beyond T, N and M: can lateral lymph node dissection treat tumour deposits in advanced low rectal carcinoma?

“…We thank Peparini for their interest in our study 1 . Postoperative pathological findings are helpful in determining the indications for adjuvant therapy.…”

Total neoadjuvant therapy for locally advanced rectal cancer: the fuse is lit

“…Of course, choosing the right patient for neoadjuvant therapy is essential 8 , so it is crucial to achieve excellence in MRI staging as it is possible to predict those at risk of relapse 9 . This has been highlighted by the recent focus on extramesorectal nodal metastatic burden, and how it should be managed with combination therapy and surgery 10,11 . Prognosis may be affected more by surgical complications than by chemotherapy issues 2–12 , so why not consider TNT to improve oncological outcomes?…”