Long-term results of phase 2 OPRA trial of organ preservation with total neoadjuvant therapy for rectal adenocarcinoma

The phase 2 OPRA trial randomized patients with stage II or III rectal adenocarcinoma to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved complete or near-complete respons after finishing treatment were offered watch-and-wait (WW), while total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS), and the secondary end point was TME-free survival. The median follow-up was 5.1 years. The 5-year DFS rates were 71% and 69% vor INCT-CRT and CRT-CNCT, respectively (p=0.68), while TME-free survival was 39% and 54%, respectively (p=0.12). Among patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64%) and patients in WW who underwent TME after regrowth (64%). The authors conclude that updated analysis continues to show long-term organ preservation in half of the patients treated with total neoadjuvant therapy for rectal cancer. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.