INDICATIONS FOR ENDOSCOPIC TREATMENT AND ADJUVANT CHEMORADIOTHERAPY IN PATIENTS WITH HIGH-RISK RECTAL SUBMUCOSAL INVASIVE CANCER (JCOG1612)

Abstract

Surgical resection with lymph node dissection is the current standard of treatment for high-risk lower rectal submucosal invasive cancer after endoscopic or surgical local resection. However, surgery affects the patientsʼ quality of life due to stoma placement or impaired anal sphincter function. The 5-year disease-free survival rate of patients who underwent adjuvant chemoradiotherapy (CRT) after local resection is comparable to those who underwent surgery. Therefore, we hypothesize that adjuvant CRT, consisting of capecitabine and radiotherapy, can be an option or a new standard of treatment for patients with high-risk lower rectal submucosal invasive cancer after local resection. The Gastrointestinal Endoscopy Study Group and the Colorectal Cancer Study Group of the Japan Clinical Oncology Group (JCOG) planned the study (JCOG1612) aimed at confirming the utility of adjuvant chemoradiotherapy for rectal submucosal invasive cancer after local resection to surgical treatment. JCOG1612 is designed as a multi-institutional, single-arm trial. The primary endpoint is 5-year relapse-free survival (RFS). The secondary endpoints are 10-year RFS; 5-year and 10-year overall survival (OS), 5-year and 10-year local RFS, 5-year and 10-year proportion of anus-preservation without stoma, Wexner score, low anterior resection syndrome score, adverse events, and severe adverse events. During the 4-year trial period, 210 patients will be accrued from about 70 Japanese institutions. The participants will include patients who 1) are aged 20-75 years; 2) have an Eastern Cooperative Oncology Group Scale of Performance Status of 0-1; 3) have undergone complete en bloc resection performed by local resection with vertical margin-negative as the pathological diagnosis; 4) have no lymph node and distant metastasis by diagnostic imaging; and 5) rejected the current standard of treatment (surgical resection with lymph node dissection). The trial treatment is chemotherapy with capecitabine (days 1-5, 8-12, 15-19, 22-26, and 29-33; 1800-3000 mg/day) in combination with radiotherapy (45 Gy in 25 fractions) for primary tumor bed and mesorectum after local resection. All registered patients will be followed-up for at least 10 years after enrolment. Colonoscopy, physical examination, and enhanced computed tomography of the chest, abdomen, and pelvis will be performed every 6 months for the first 3 years after the termination of protocol treatment, and yearly thereafter for the next 7 years. This study was approved by the Accredited Clinical Research Review Board on October 15, 2018; published on Japan Registry of Clinical Trials on January 11, 2019; and registration began on January 16.