Refining the Multivariable Predictive‐Prognostic <scp>PREDICTR</scp> ‐ <scp>OPC</scp> Model for Survival in Surgical Escalation for Oropharyngeal Squamous Cell Carcinoma

OBJECTIVES: The PREDICTR-OPC model is the only prognostic classifier for oropharyngeal squamous cell carcinoma (OPSCC) also predictive of surgical outcomes. Of the four biomarkers included, survivin contributes minimally and presents practical limitations. This study aimed to refine and simplify the model by removing survivin, then re-assess its prognostic predictive performance compared to the original. METHODS: This retrospective cohort study analyzed a multi-center training cohort (n = 600) and an external validation cohort (n = 385) of OPSCC patients. Tumor biopsies were stained for p16, high-risk human papillomavirus (HR-HPV) DNA, tumor-infiltrating lymphocytes (TILs), and survivin and independently scored by at least three certified pathologists. Cox proportional hazards models assessed overall survival (OS), comparing three-biomarker (p16, HR-HPV, TILs) and four-biomarker models. Hazard ratios (HRs) for OS were estimated in the validation cohort, adjusting for covariates. Discrimination, calibration, and decision curve analysis (DCA) evaluated performance and clinical utility. RESULTS: Among 985 patients (median age: 57 years), median OS = 8.8 years (95% CI: 6.9-10.5). The three-biomarker model yielded HR = 4.10 (95% CI: 2.41-6.98, p < 0.001) for high- vs. low-risk groups in the validation cohort, comparable to the four-biomarker model (HR = 4.24, p < 0.001). Surgery was associated with improved OS in high-risk (HR = 0.45, p = 0.001) but not low-risk (HR = 0.83, p = 0.72) patients, consistent with the original model. The models performed similarly across all metrics (e.g., Concordance Index: 0.71 vs. 0.72; Brier Score: 0.22 for both) as was model fit (Likelihood Ratio Test: p = 0.066). DCA revealed comparable clinical benefit. CONCLUSION: Removing survivin preserves PREDICTR-OPC's predictive performance, offering a more cost-effective, easier-to-implement tool for OPSCC treatment recommendations.