Neoadjuvant chemotherapy with FOLFOXIRI plus lateral lymph nodes dissection for the treatment of resectable rectal cancer with lateral lymph node metastasis: A single-arm, investigator-initiated, phase II trial.

3533 Background: There is a lack of standardization in the comprehensive treatment strategies for rectal cancer with lateral lymph node metastasis (LLNM), which results in an unfavorable oncological outcome. We conducted the present phase II trial by performing neoadjuvant chemotherapy with 5-fluorouracil, irinotecan, and oxaliplatin (FOLFOXIRI) regimen plus lateral lymph node dissection (LLND) for resectable rectal cancer with LLNM to decrease the lateral recurrence and distant metastasis rates. Methods: This prospective, single-arm phase II trial was conducted from April 2018 to February 2023, and included patients with cT3-4aN+M0 resectable rectal cancer and clinical suspicion of LLNM based on preoperative MRI. Patients were treated with three cycles of FOLFOXIRI, and those with evidence of treatment response continued to receive two cycles of FOLFOXIRI. Total mesorectal excision plus LLND was performed at 3-4 weeks after completing the last cycle of preoperative chemotherapy, followed by 3 cycles of XELOX. Results: A total of 58 patients engaged in this research, and 53 were finally enrolled. The pathological examination detected microscopic LLNM in 12 (22.6%) patients. The pathologic complete response (pCR) rate was 11.3% (6/53), and the downstaging (ypstage 0 to 1) rate was 30.2% (16/53). DFS events were observed in 7 patients, and OS events were reported in 2 patients after a median follow-up of 30 months. The 3-year DFS rate was 88.3%, the 3-year local recurrence-free survival rate was 94.7%, and the 3-year OS rate was 91.3%. There were 14 (26.4%) cases with six grade 3/4 adverse events. Conclusions: Neoadjuvant chemotherapy with the FOLFOXIRI regimen plus LLND can significantly reduce the risk of local recurrence and distant metastasis in resectable rectal cancer with LLNM, which may be a new treatment option. Clinical trial information: NCT04850027 . Variable, n (%) Total pCR (ypT0N0), n (%) 6 (11.3%) Total LNs harvested Median (IQR) 30 (24~40) LLNs harvested Median (IQR) 12 (8~17) Pathological T category ypTis 1 (1.9%) ypT0 6 (11.3%) ypT1 2 (3.8%) ypT2 11 (20.8%) ypT3 31 (58.5%) ypT4 2 (3.8%) Pathological N category ypN0 30 (56.6%) ypN1 15 (28.3%) ypN2 8 (15.1%) Pathological stage 0 6 (11.3%) I 10 (18.9%) II 17 (32.1%) III 20 (37.7%) Tumor regression grade* 0 1 (1.9%) 1 21 (39.6%) 2 12 (22.6%) 3 12 (22.6%) 4 5 (9.4%) Pathological LLN status Positive 12 (22.6%) Negative 41 (77.4%) Histologic grade Moderate 42 (79.2%) Poor/Mucinous/signet 11 (20.8%) Blood vessel invasion Yes 11 (20.8%) No 42 (79.2%) Perinervous invasion Yes 12 (22.6%) No 41 (77.4%)