Adjuvant, neoadjuvant and surgical treatment for locally advanced cervical cancer: A network meta-analysis.

Abstract

5526 Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC). Alternative strategies, including induction chemotherapy followed by CCRT (IC + CRRT) and CCRT with immune checkpoint inhibitors (CCRT + ICI), have shown promising yet conflicting results. This study used a network meta-analysis (NMA) to compare the efficacy of these treatments. Methods: A systematic review identified RCTs published until November 25, 2024, comparing treatments for FIGO stage IB2-IVA LACC, including neoadjuvant chemotherapy, adjuvant chemotherapy (ACT), radiotherapy (RT), CCRT+ICI, surgery, or combinations. Progression-free survival (PFS) and overall survival (OS) were evaluated. Hazard ratios (HRs) were extracted or reconstructed from Kaplan–Meier curves using IPDfromKM. Bayesian NMA was conducted with random-effects models using the gemtc package. Three chains were run for 600,000 iterations, discarding the first 60,000 as burn-in. Results included 95% credible intervals (CrIs) for HRs. Treatment rankings were derived using the surface under the cumulative ranking curve (SUCRA), and probabilities of treatment superiority (SP) were calculated. Results: A total of 46 trials (49 reports) involving 13,895 patients were included in the analysis, with 89% having squamous cell histology. CCRT and RT were the most frequently used comparator treatments. Data from 39 trials (11,727 patients) were analyzed for OS, comparing 10 treatment regimens. CCRT significantly improved OS compared to RT (HR 0.76; 95% credible interval [CrI] 0.63–0.94) and showed a trend toward superiority over surgery (HR 0.71; 95% CrI 0.49–1.02; SP = 96.9%). However, no significant differences were observed between CCRT and either CCRT + ICI (SP = 6.2%) or IC + CCRT (SP = 28.3%). CCRT + ACT further improved OS compared to RT (HR 0.60) and surgery (HR 0.56). CCRT + ICI also demonstrated superiority over RT and surgery. Based on SUCRA scores, CCRT + ICI ranked highest for OS. For PFS, data from 37 trials (12,025 patients) were analyzed. CCRT demonstrated superiority over RT (HR 0.77; 95% CrI 0.65–0.92). No significant differences were observed between CCRT and other regimens, including CCRT + ICI (SP = 5.4%), IC + CCRT (SP = 34.1%), and CCRT + ACT (SP = 29.2%). Both CCRT + ACT and CCRT + ICI were superior to RT alone (HR 0.71 and HR 0.59, respectively). Additionally, CCRT + ICI was more effective than IC + RT. In a subgroup analysis of trials limited to squamous cell carcinoma, CCRT was superior to CCRT + ACT (HR 0.4; 95% CrI 0.2–0.85). Based on SUCRA scores, CCRT + ICI ranked highest for PFS. Conclusions: CCRT demonstrates consistent superiority in OS and PFS over RT and surgery, with comparable efficacy to regimens such as CCRT + ACT, IC + CCRT, and CCRT + ICI. These findings reaffirm CCRT’s position as the cornerstone treatment for LACC, while supporting the potential of novel strategies in select populations.