Radiotherapy-to-Surgery Interval After Induction Total Neoadjuvant Therapy for Rectal Cancer: Perioperative Outcomes and Oncologic Quality of Total Mesorectal Excision.

Abstract

Background: The interval from radiotherapy completion to surgery may affect pelvic fibrosis, operative difficulty, postoperative morbidity, and quality of rectal cancer resection. In total neoadjuvant therapy (TNT), however, this interval has different clinical content according to treatment sequence. We evaluated whether radiotherapy-to-surgery timing after induction TNT was associated primarily with perioperative morbidity and surgical oncologic quality.

Methods: We performed a retrospective cohort study of patients with locally advanced rectal adenocarcinoma treated at a tertiary cancer center from January 2020 through December 2024. The primary analysis included 94 patients receiving induction TNT, in whom systemic chemotherapy preceded radiotherapy. The radiotherapy-to-surgery interval was modeled continuously per 4-week increase; categories of ≤ 8, > 8-12, and > 12 weeks were retained for descriptive reporting only because the early strata were sparse. The primary endpoint was Clavien-Dindo grade ≥ III morbidity within 30 days. Secondary endpoints included reoperation, readmission, anastomotic leak, conversion, operative time, blood loss, length of stay, mesorectal quality, resection margins, and lymph-node yield. Pathological complete response (pCR) and recurrence-free survival were exploratory oncologic endpoints. Consolidation TNT was examined separately because its measured interval contains post-radiotherapy chemotherapy.

Results: Among 94 patients treated with induction TNT, the median radiotherapy-to-surgery interval was 143.5 days (IQR 104.8-259.3). Major morbidity occurred in 17/94 (18.1%), reoperation in 12/93 (12.9%), and readmission in 9/94 (9.6%). Median operative time was 279.5 min, blood loss 100 mL, and length of stay 4 days. Complete or near-complete mesorectal quality was documented in 73/91 (80.2%), R0 resection in 88/94 (93.6%), and median lymph-node yield was 9 (IQR 6-15). Each additional 4 weeks was not associated with major morbidity (adjusted OR 0.886, 95% CI 0.748-1.050; p = 0.164), reoperation (OR 0.910, 95% CI 0.755-1.096; p = 0.320), incomplete mesorectal excision (OR 1.113, 95% CI 0.971-1.275; p = 0.125), operative time (adjusted β - 0.4 min, 95% CI -5.5 to 4.8; p = 0.893), blood loss (1.4% change, 95% CI -4.8% to 7.9%; p = 0.668), or length of stay (-0.1% change, 95% CI -3.0% to 2.9%; p = 0.958). Exploratory analyses found no association with pCR or recurrence-free survival.

Conclusions: After adjustment for radiotherapy course, variation in radiotherapy-to-surgery timing was not associated with major postoperative morbidity, operative burden, or incomplete mesorectal excision. R0 resection was achieved in 93.6% of patients, while margin events were too infrequent for stable adjusted modeling. Lymph-node yield showed no statistically significant association with interval duration. pCR and recurrence analyses were exploratory and did not show an interval association. Timing should be interpreted according to TNT sequence because consolidation therapy structurally prolongs the radiotherapy-to-surgery interval.