Short‐term outcomes of a prospective multicenter phase <scp>II</scp> trial of total neoadjuvant therapy for locally advanced rectal cancer in <scp>Japan</scp> (<scp>ENSEMBLE</scp>‐1)

Aim To evaluate the feasibility and safety of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC) Japan. Methods This prospective, multicenter, open-label, single-arm phase II trial was conducted at five institutions. The key eligibility criteria were age ≥ 20 years, LARC within 12 cm from anal verge, cT3-4N0M0 or TanyN+M0 time diagnosis that enabled curative resection. Preoperative short-course radiation (SCRT) 5 Gy × days (total 25 Gy) + CAPOX (six courses) followed by mesorectum excision (TME) treatment protocol. Non-operative management (NOM) allowed if clinical complete response (cCR) obtained preoperative evaluation. primary endpoint pathological (pCR) rate. Results Thirty (male, n = 26; female, 4; median age, 62.5 [44–74] years; cT [T2, 1; T3, 25; T4, 4]; cN [N0, 13; N1, N2, 4]) enrolled. final analysis included 30 total. completion rates 100% for SCRT 83% CAPOX. TME NOM performed seven patients, respectively. pCR observed six (30% [95% CI 14.0%–50.8%]). met. pCR+cCR 13 (43.3%) patients. There no treatment-related deaths. Grade ≥3 (CTCAE ver. 5.0) adverse events (≥20%), including diarrhea (23.3%) neutropenia (23.3%). follow-up period 15.6 (10.5–22.8) months, recurrence regrowth NOM. Conclusions ENSEMBLE-1 demonstrated satisfactory cCR, well-tolerated TNT