Outcomes of Stage IVA Cervical Cancer Treated with Radiotherapy: A Systematic Review and Meta-Analysis.

Abstract

FIGO stage IVA cervical cancer, defined by bladder or rectal mucosal invasion without distant spread, is uncommon and understudied. This first meta-analysis exclusively on stage IVA cervical cancer aimed to synthesize survival and morbidity outcomes and identified prognostic factors influencing disease control and fistula formation. Following PRISMA 2020 guidelines (XXXXXXX. XXXXXXXXXXXXXX), PubMed, Embase, and Web of Science were systematically searched through February 2025 to identify studies reporting clinical outcomes in patients with FIGO stage IVA cervical cancer treated with definitive photon-based radiotherapy, either alone or in combination with concurrent chemotherapy or brachytherapy. Eleven studies (10 retrospective, 1 prospective) including 492 patients met inclusion criteria. Pooled 2-, 3-, and 5-year overall (OS) and disease-free survival (DFS) and fistula incidence were calculated using random-effects models. Study quality was assessed using the NIH Case-Series Tool. The pooled 2-, 3-, and 5-year DFS rates were 41.5% (95% CI: 28.09-54.97), 34.2% (95% CI: 21.08-47.34), and 30.9% (95% CI: 15.98-45.81) respectively; OS rates were 56.0% (95% CI: 46.21-65.90), 45.9% (95% CI: 35.86-55.92) and 34.8% (95% CI: 26.38-43.28). Weighted median OS and DFS were 33.6 and 15.6 months. The pooled vesicovaginal or rectovaginal fistula incidence was 23.7% (95% CI, 12.9-34.6). Adverse prognostic factors included pelvic nodal involvement, hydronephrosis, rectal invasion, omission of brachytherapy, and total EQD2 < 80-85 Gy. Concurrent chemoradiation and completion of brachytherapy significantly improved survival. Results were robust on sensitivity analyses. Stage IVA cervical cancer carries poor long-term outcomes despite curative-intent therapy, with 5-year OS around 35% and substantial late morbidity. Durable pelvic control remains the key therapeutic challenge. Concurrent chemoradiation with adequate-dose brachytherapy is essential for cure, while omission markedly worsens prognosis. Future stage IVA-specific trials integrating image-guided adaptive brachytherapy, advanced radiotherapy platforms, and systemic intensification are needed to improve survival and reduce fistula risk.