Background: Cervical cancer remains a major global health concern, with high recurrence rates in advanced stages. [18F]FDG PET/CT provides prognostic biomarkers such as SUV, MTV, and TLG, though these are not routinely integrated into clinical protocols. Radiomics offers quantitative analysis of tumor heterogeneity, supporting risk stratification.

Purpose: To evaluate the prognostic value of clinical and radiomic features for disease-free survival (DFS) in locoregionally advanced cervical cancer using machine learning (ML).

Methods: Sixty-three patients (mean age 47.9 ± 14.5 years) were diagnosed between 2015 and 2020. Radiomic features were extracted from pre-treatment PET/CT (IBSI-compliant PyRadiomics). Clinical variables included age, T-stage, Dmax, lymph node involvement, SUVmax, and TMTV. Forty-two models were built by combining six feature-selection techniques (UCI, MD, MI, VH, VH.VIMP, IBMA) with seven ML algorithms (CoxPH, CB, GLMN, GLMB, RSF, ST, EV) using nested 3-fold cross-validation with bootstrap resampling. External validation was performed on 95 patients (mean age 50.6 years, FIGO IIB–IIIB) from an independent cohort with different preprocessing protocols.

Results: Recurrence occurred in 31.7% (n = 20). SUVmax of lymph nodes, lymph node involvement, and TMTV were the most predictive individual features (C-index ≤ 0.77). The highest performance was achieved by UCI + EV/GLMB on combined clinical + radiomic features (C-index = 0.80, p < 0.05). For single feature sets, IBMA + RSF performed best for clinical (C-index = 0.72), and VH.VIMP + GLMN for radiomics (C-index = 0.71). External validation confirmed moderate generalizability (best C-index = 0.64).

Conclusions: UCI-based feature selection with GLMB or EV yielded the best predictive accuracy, while VH.VIMP + GLMN offered superior external generalizability for radiomics-only models. These findings support the feasibility of integrating radiomics and ML for individualized DFS risk stratification in cervical cancer.