A phase III randomized controlled trial comparing surgery plus adjuvant chemotherapy with or without preoperative chemoradiotherapy for locally recurrent rectal cancer: A Japan Clinical Oncology Group study (JCOG1801).

TPS263 Background: Local recurrence is one of the most common forms of recurrence after curative resection for primary rectal cancer. Surgical resection is recommended for locally recurrent rectal cancer (LRRC) to achieve radical cure if the tumor is judged as resectable with negative margins. However, a high local re-recurrent risk after surgery is a major problem due to the difficulty of re-resection and the serious symptoms, such as pain or fistula, resulting from re-recurrence. Preoperative chemoradiotherapy (preCRT) is expected to improve local control after radical surgery for radiation naïve LRRC; however, high frequency of surgical complications after preCRT cannot be ignored. Due to the refractory nature and rarity of LRRC, the true impact of preCRT on oncological and surgical outcomes has not been clarified by clinical trials. The purpose of this study is to confirm the superiority of preCRT followed by surgery plus adjuvant chemotherapy over surgery plus adjuvant chemotherapy alone, in terms of local relapse-free survival for resectable LRRC. Methods: Eligibility criteria include resectable LRRC without distant metastasis, no prior pelvic irradiation, no prior surgery for LRRC, aged 20-80 years, and sufficient organ function. Eligible patients are randomized into the surgery and adjuvant chemotherapy (arm A) or preCRT followed by surgery and adjuvant chemotherapy (arm B). PreCRT consists of the standard dose of capecitabine and radiotherapy (50.4Gy). Adjuvant chemotherapy consists of mFOLFOX6, CAPOX, capecitabine, or 5FU+l-LV. The primary endpoint is local relapse-free survival (LRFS), and the secondary endpoints include overall survival, relapse-free survival, %R0 resection, incidence of adverse events, and quality of life after surgery. The 3-year LRFS of arm A is assumed to be 60% with a 13% increase expected in arm B. The sample size was calculated as 106 (53 per arm) with a one-sided alpha of 10%, power of 70%, and accrual period of 6 years. This trial was initiated on 19 August 2019. Clinical trial information: jRCTs031190076.