First-line treatment of locally advanced cervical carcinoma: An updated systematic review and Bayesian network meta-analysis

Introduction: Locally advanced cervical carcinoma (LACC) remains a significant global health issue, particularly in low- and middle-income countries (LMICs), where disease burden is highest. While cisplatin-based chemoradiotherapy (CTRT) has long been the cornerstone of first-line treatment, its toxicities, including nephrotoxicity and hematologic adverse events, limit its use in certain patients. Advances in systemic therapies, including immune checkpoint inhibitors and induction chemotherapy, offer new avenues for improving outcomes. This study aimed to evaluate the efficacy of various first-line regimens for LACC through a systematic review and Bayesian network meta-analysis (NMA), focusing on overall survival (OS) and progression-free survival (PFS). Materials and Methods: This analysis adhered to PRISMA guidelines and included Phase III randomized controlled trials (RCTs) evaluating first-line treatments for LACC. The primary outcome was OS, expressed as hazard ratios (HRs) with 95% confidence intervals (CIs), while PFS was secondary. A comprehensive search of PubMed, EMBASE, and Cochrane Library was conducted through November 2024. Statistical analysis used a Bayesian NMA framework, with treatments ranked by surface under the cumulative ranking curve (SUCRA). Results: Pembrolizumab + CTRT improved OS (HR, 0.67; 95 % CI, 0.50-0.90), while induction chemotherapy with carboplatin/paclitaxel followed by CTRT showed significant benefit (HR, 0.60; 95 % CI, 0.40-0.90). RT + cisplatin and 5-fluorouracil (5-FU) also improved OS (HR, 0.66; 95 % CI, 0.44-0.99), ranking highest in SUCRA analysis (98 %). Conclusion: Three promising strategies-pembrolizumab-based regimens, induction chemotherapy followed by CTRT, and RT + CDDP + 5-FU-offer substantial survival benefits, advancing treatment options for LACC.