Comparative Efficacy of Therapies for Locally Advanced Cervical Cancer

Concurrent chemoradiotherapy (CCRT) remains the standard treatment for locally advanced cervical cancer (LACC). Alternative approaches, such as induction chemotherapy followed by CCRT (IC + CCRT) and CCRT combined with immune checkpoint inhibitors (CCRT + ICI), have yielded promising but inconsistent outcomes. This study conducted a network meta-analysis (NMA) to evaluate and compare the effectiveness of these treatment strategies.

The results will be presented at the American Society of Clinical Oncology 2025 Annual Meeting, from May 30 to June 3, 2025.

A systematic review identified randomized controlled trials (RCTs) published up to November 25, 2024, that compared treatment options for FIGO stage IB2-IVA locally advanced cervical cancer (LACC), including neoadjuvant chemotherapy, adjuvant chemotherapy (ACT), radiotherapy (RT), CCRT + ICI, surgery, and various combinations.

Progression-free survival (PFS) and overall survival (OS) were assessed. Hazard ratios (HRs) were either extracted directly or reconstructed from Kaplan-Meier curves using the IPDfromKM method. The analysis reported HRs with 95% credible intervals (CrIs), and treatment rankings were determined using the surface under the cumulative ranking curve (SUCRA). Superiority probabilities (SP) were also calculated for each treatment.

A total of 46 trials including 13,895 patients were included, with squamous cell carcinoma accounting for 89% of cases. CCRT and RT were the most used comparator arms. Overall survival (OS) data was available from 39 trials (11,727 patients), covering 10 treatment strategies. CCRT significantly improved OS compared with RT (HR, 0.76; 95% CrI, 0.63-0.94) and showed a strong trend toward superiority over surgery (HR, 0.71; 95% CrI, 0.49-1.02; SP, 96.9%). However, no significant differences were found (CCRT, CCRT + ICI, SP, 6.2% or IC + CCRT, SP, 28.3%).

Adding adjuvant chemotherapy to CCRT (CCRT + ACT) resulted in further OS benefit compared with both RT (HR, 0.60) and surgery (HR, 0.56). CCRT + ICI also demonstrated superiority over both RT and surgery. Based on SUCRA rankings, CCRT + ICI was the top-ranked regimen for OS.

PFS was assessed in 37 trials (12,025 patients). CCRT again outperformed RT (HR, 0.77; 95% CrI, 0.65-0.92), but no significant differences were noted 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 (HR, 0.71 and HR, 0.59, respectively). In addition, CCRT + ICI outperformed IC + RT.

In a subgroup analysis limited to patients with squamous cell carcinoma, CCRT alone was superior to CCRT + ACT (HR, 0.4; 95% CrI, 0.2-0.85). SUCRA rankings again placed CCRT + ICI as the top regimen for PFS.

“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,” the researchers noted.