Evolving Systemic Intensification Strategies Beyond CCRT in Locally Advanced Cervical Cancer

Concurrent chemoradiotherapy (CCRT) remains the standard of care for locally advanced cervical cancer (LACC); however, 30-40% of patients experience recurrence, prompting evaluation of systemic treatment intensification to improve outcomes over CCRT alone. This critical review synthesizes evidence from PubMed, Embase, and the Cochrane Library up to January 2026, evaluating clinical trials of intensification strategies categorized by treatment timing: neoadjuvant, concurrent, and adjuvant modalities. Historical attempts to intensify treatment through adjuvant chemotherapy have failed to confer survival benefits with the regimens studied, often increasing toxicity without efficacy (OUTBACK). However, recent Phase III trials have reported survival benefits with specific treatment regimens. Specifically, induction chemotherapy followed by CCRT (INTERLACE) and pembrolizumab with CCRT followed by maintenance (KEYNOTE-A18) have demonstrated significant improvements in overall survival, whereas additional concurrent cytotoxic agents have not consistently improved outcomes and may increase toxicity. CCRT remains the cornerstone; intensification should follow the tested regimen, eligibility criteria, and toxicity profile. PD-L1-based selection and the independent benefit of adjuvant immunotherapy require further validation.