Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Definitive Chemoradiotherapy for Locally Advanced Cervical Cancer: A Comparative Retrospective Cohort Study

Abstract

Background: Optimal management of FIGO 2018 stage IB3–IIA cervical cancer remains debated. Objectives: This study compared oncological outcomes and toxicity profiles between 2 primary treatment paradigms for locally advanced disease: neoadjuvant chemotherapy followed by radical surgery (NACT_RS) and definitive chemoradiotherapy (CRT). Methods: This retrospective analysis included 81 consecutive patients with tumors ≥ 4 cm (FIGO stage IB3-IIA) who were treated between 2021 and 2024. Patients received either NACT_RS (n = 31) or CRT (n = 50). Patient characteristics, treatment-related complications graded according to the Common Terminology Criteria for Adverse Events version 5.0, and survival outcomes were compared. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression. Results: The NACT_RS and CRT groups were well matched for baseline tumor size, stage, and histology. Grade ≥ 2 late complications were significantly more frequent in the CRT group (64.0%) than in the NACT_RS group (6.5%) (P < 0.001), driven mainly by high rates of vaginal stenosis and dyspareunia. Notably, the 12 surgical patients who required adjuvant radiotherapy also had a lower rate of late complications (16.7%) than the definitive CRT group. Three-year PFS was significantly better in the NACT_RS arm (96%) than in the CRT arm (74%) (P = 0.013). Similarly, 3-year disease-specific OS was 100% for NACT_RS and 81% for CRT (P = 0.011). In multivariate analysis, CRT was associated with an 8.2-fold higher risk of recurrence than NACT_RS (HR = 8.16; 95% CI, 1.07 - 62.36; P = 0.043). Conclusions: In this cohort of patients with locally advanced cervical cancer, NACT_RS was associated with superior survival outcomes and substantially lower rates of long-term morbidity compared with definitive CRT. NACT_RS appears to be a viable and potentially superior strategy for downstaging larger tumors to achieve excellent oncologic outcomes while minimizing the substantial late toxicities associated with pelvic radiotherapy.