Surgical complications and perioperative outcomes following total mesorectal excision in patients with locally advanced rectal cancer treated with short-course radiotherapy and chemo-immunotherapy: Updated data from the phase II Averectal trial.

Abstract

e15667 Background: Total mesorectal excision (TME) in locally advanced rectal cancer (LARC) is challenging, particularly after neoadjuvant therapy. We analyzed surgical complications and perioperative outcomes from the Averectal trial (NCT03503630). Methods: The Averectal trial is a phase II, open-label, single-arm, multicenter study evaluating short-course radiotherapy (SCRT: 25 Gy in 5 fractions), followed by 6 cycles of mFOLFOX-6 plus avelumab (10 mg/kg every 2 weeks), with TME performed 4-6 weeks post-treatment in microsatellite stable (MSS) LARC. Surgeries were performed by experienced rectal surgeons under strict quality control using 2013 College of American Pathologists criteria. Operative parameters (approach, duration, blood loss, technique) and pathological features (CRM, EMVI, TRG) were recorded. Postoperative complications were graded by Clavien–Dindo classification, and serious adverse events (SAEs) documented. Results: Of 44 patients enrolled, 40 underwent TME (38 low anterior resections, 2 abdominoperineal resections). Surgical approach was open in 20 (50.0%), laparoscopic in 17 (42.5%), and robotic in 3 (7.5%). Diverting ileostomy was performed in 35 (87.5%). R0 resection was achieved in 32/34 (94.1%), with negative CRM in 31/34 (91.2%), TRG 0 in 17/39 (43.6%) and EMVI in 2/35 (5.7%). Median lymph node yield was 17 (range 0-42); 29/34 (85.3%) were node-negative. Median operative time was 268 minutes; median blood loss 182 mL with 2 patients receiving blood transfusion. Postoperative complications occurred in 16/40 patients (40%), averaging 1.5 per patient (range 1-4), totaling 48 events: Grade I (11 complications, 22.9%), Grade II (23 complications, 47.9%), Grade III (11 complications, 22.9%), and Grade IV (3 complications, 6.2%). Thirty-six complications (75.0%) were classified as SAEs. Frequent complications included ileus or bowel obstruction (8), abdominal abscess or infection (8), anastomotic leak (5), electrolyte disturbances (4), acute kidney injury (3), constipation (3), wound dehiscence (2), hernia (2), tumor perforation (1), and urinary retention (1). Most resolved within 1 week; 2 patients required > 1 month hospitalization, and 1 developed permanent sexual dysfunction. No significant difference was noted between open and minimally invasive surgery. Pathologic complete response was achieved in 37.5%. Local recurrence at 3 years occurred in 2.5%. Three patients (7.5%) died during follow-up, all due to disease progression unrelated to surgical complications. Conclusions: SCRT followed by mFOLFOX-6 plus avelumab and TME resulted in acceptable surgical morbidity and favorable oncologic outcomes. These findings support the safety and feasibility of this chemo-immunotherapy approach in MSS LARC. Clinical trial information: NCT03503630 .