Nonoperative Rectal Cancer Management With Short-Course Radiation Followed by Chemotherapy: A Nonrandomized Control Trial

Short-course radiation therapy results in higher pathologic complete response than long-course chemoradiation therapy in rectal adenocarcinoma. All definitive treatment experiences with nonoperative intent have used long-course chemoradiation. This prospective clinical trial of 20 patients is the first experience of nonoperative management with short-course radiation followed by chemotherapy. We observed a high clinical complete response rate with no severe late toxicity. Purpose: Short-course radiation therapy (SCRT) and nonoperative management are emerging paradigms for rectal cancer treatment. This clinical trial is the first to evaluate SCRT followed by chemotherapy as a nonoperative treatment modality. Methods: Patients with nonmetastatic rectal adenocarcinoma were treated on the single-arm, Nonoperative Radiation Management of Adenocarcinoma of the Lower Rectum study of SCRT followed by chemotherapy. Patients received 25 Gy in 5 fractions to the pelvis followed by FOLFOX x8 or CAPOX x5 cycles. Patients with clinical complete response (cCR) underwent nonoperative surveillance. The primary end point was cCR at 1 year. Secondary end points included safety profile and anorectal function. Results: From June 2016 to March 2019, 19 patients were treated (21% stage I, 32% stage II, and 47% stage III disease). At a median follow-up of 27.7 months for living patients, the 1-year cCR rate was 68%. Eighteen of 19 patients are alive without evidence of disease. Patients with cCR versus without had improved 2-year disease-free survival (93% vs 67%; P =.006), distant metastasis-free survival (100% vs 67%; P =.03), and overall survival (100% vs 67%; P =.03). Involved versus uninvolved circumferential resection margin on magnetic resonance imaging was associated with less initial cCR (40% vs 93%; P =.04). Anorectal function by Functional Assessment of Cancer Therapy-Colorectal cancer score at 1 year was not different than baseline. There were no severe late effects. Conclusions: Treatment with SCRT and chemotherapy resulted in high cCR rate, intact anorectal function, and no severe late effects. NCT02641691. (c) 2021 Elsevier Inc. All rights reserved.