Non-Operative Management of Rectal Cancer with Adjuvant Chemotherapy after Chemoradiotherapy (NORMANDY): Prospective Study

Abstract

Purpose: Non-operative management (NOM) has emerged as a promising organ-preserving strategy for patients with rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (CRT). However, no standardized treatment protocol has been established for watch-and-wait strategies.

Materials and methods: This prospective study evaluated oncological outcomes of NOM combined with four months of adjuvant capecitabine. Patients with resectable rectal cancer (≤8 cm from the anal verge, cT2-4 or N+) underwent CRT (50-54 Gy in 25-27 fractions with capecitabine). Eight weeks post-CRT, a multidisciplinary team assessed cCR. Patients achieving cCR received six cycles of capecitabine (2 weeks on/1 week off) and were actively monitored.

Results: Among 89 patients receiving CRT (2018-2023), 17 (19%) achieved cCR and were included. The median age was 65 years, and 65% were male. Eleven (65%) completed all six cycles of adjuvant therapy. After a median follow-up of 31.4 months, 11 patients (65%) remained disease-free. Local regrowth occurred in six patients (35%) with 2- and 4-year rates of 34.5% and 47.6%, respectively. Five underwent radical surgery, and one received transanal excision with systemic chemotherapy. At the time of assessment, 15 patients (88%) showed no evidence of disease, while two (12%) received palliative chemotherapy. All patients were alive.

Conclusion: NOM with adjuvant capecitabine showed promising oncological outcomes, offering an alternative to passive watch-and-wait approaches. Further refinement through multidisciplinary strategies is warranted.

Keywords: Capecitabine; Chemoradiotherapy; Rectal Neoplasms; Watchful waiting.