A phase III randomized trial evaluating the quality of life impact of a tailored versus systematic use of defunctioning ileostomy following total mesorectal excision for rectal cancer-GRECCAR 17 trial protocol.

AIM: The systematic use of a defunctioning ileostomy for 2-3 months postoperatively to protect low colorectal anastomosis (<7 cm from the anal verge) has been the standard practice after total mesorectal excision (TME). However, stoma-related complications can occur in 20%-60% of cases, which may lead to prolonged inpatient care, urgent reoperation and long-term definitive stoma. A negative impact on quality of life (QoL) and increased healthcare expenses are also observed. Conversely, it has been reported that patients without a defunctioning stoma or following early stoma closure (days 8-12 after TME) have a better functional outcome than patients with systematic defunctioning stoma in situ for 2-3 months. METHOD: The main objective of this trial is to compare the QoL impact of a tailored versus systematic use of a defunctioning stoma after TME for rectal cancer. The primary outcome is QoL at 12 months postoperatively using the European Organization for. Research and Treatment of Cancer QoL questionnaire QLQ-C30. Among 29 centres of the French GRECCAR network, 200 patients will be recruited over 18 months, with follow-up at 1, 4, 8 and 12 months postoperatively, in an open-label, randomized, two-parallel arm, phase III superiority clinical trial. The experimental arm (arm A) will undergo a tailored use of defunctioning stoma after TME based on a two-step process: (i) to perform or not a defunctioning stoma according to the personalized risk of anastomotic leak (defunctioning stoma only if modified anastomotic failure observed risk score ≥2) and (ii) if a stoma is fashioned, whether to perform an early stoma closure at days 8-12, according to clinical (fever), biochemical (C-reactive protein level on days 2 and 4 postoperatively) and radiological postoperative assessment (CT scan with retrograde contrast enema at days 7-8 postoperatively). The control arm (arm B) will undergo systematic use of a defunctioning stoma for 2-3 months after TME for all patients, in keeping with French national and international guidelines. Secondary outcomes will include comprehensive analysis of functional outcomes (including bowel, urinary and sexual function) again up to 12 months postoperatively and a cost analysis. Regular assessments of anastomotic leak rates in both arms (every 50 randomized patients) will be performed and an independent data monitoring committee will recommend trial cessation if this rate is excessive in arm A compared to arm B. CONCLUSION: The GRECCAR 17 trial is the first randomized trial to assess a tailored, patient-specific approach to decisions regarding defunctioning stoma use and closure after TME according to personalized risk of anastomotic leak. The results of this trial will describe, for the first time, the QoL and morbidity impact of selective use of a defunctioning ileostomy and the potential health economic effect of such an approach.

A phase III randomized trial evaluating chemotherapy followed by pelvic reirradiation versus chemotherapy alone as preoperative treatment for locally recurrent rectal cancer - GRECCAR 15 trial protocol.

AIM: Treatment strategies in locally recurrent rectal cancer (LRRC) are complex and need to be balanced against previous treatments received for the primary rectal cancer. Radiotherapy is an important component of treatment in LRRC. However, there is little high-quality evidence on the role of reirradiation in this cohort. Therefore, the aim of this trial is to assess the efficacy of neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone on the rate of curative surgery (R0) in previously irradiated patients with LRRC. METHOD: GRECCAR 15 is a prospective, multicentre, open-label, outcome assessor-blinded, superiority randomized controlled phase III clinical trial comparing neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone in patients with LRRC previously irradiated for the primary cancer. Adult patients (>18 years old) with a histologically proven resectable LRRC, who have previously received pelvic radiotherapy for their primary rectal cancer at a dose of 25-50.4 Gy, and an Eastern Cooperative Oncology Group performance status of <2 will be eligible to participate. The pelvic reirradiation will consist of conformational intensity-modulated external irradiation, delivering a dose of 30.6 Gy with concomitant chemotherapy using capecitabine. The primary outcome of this trial is the R0 resection rate. Overall, GRECCAR 15 aims to recruit 186 patients to detect an absolute difference of 20% in the R0 resection rate with 80% power and 5% two-sided significance level. CONCLUSION: The GRECCAR 15 trial is the first, definitive, phase III trial to investigate reirradiation in LRRC. The results of this trial will inform definitively the neoadjuvant treatment strategy in previously irradiated patients and assess whether there is any associated benefit of reirradiation in combination with induction chemotherapy in improving R0 resection rates.