Individual and Population Comparisons of Surgery and Radiotherapy Outcomes in Prostate Cancer Using Bayesian Multistate Models

Abstract

Whether surgery or radiotherapy is the preferred treatment for patients with localized prostate cancer continues to be debated, and randomized clinical trials cannot yet fully address this question. Furthermore, there may be heterogeneity in responses, and the optimal treatment for a patient will depend on his clinical and tumor characteristics. To use a unified statistical approach to compare the association of surgery and radiotherapy with both metastatic clinical failure (CF) and survival in localized prostate cancer and to develop an online calculator for individualized, treatment-specific outcome prediction. Cohort study for statistical analysis and development of individualized predictions using Bayesian multistate models that jointly consider both CF and survival and adjust for confounding factors. This study used data from patients treated at the University of Michigan between January 1, 1996, and July 1, 2013, with detailed information on treatment, patient and tumor characteristics, and outcomes. Primary analyses were performed in 2017 and 2018. Participants were a cohort of 4544 patients with localized prostate cancer undergoing primary treatment. Radical prostatectomy and external beam radiotherapy. The clinical outcomes were metastatic CF, death after CF, and death from other causes. The adjustment factors were age, prostate gland volume, prostate-specific antigen level, comorbidities, Gleason score, perineural invasion, cT category, race, and treatment year. An online calculator was developed to estimate risks for multiple outcomes for any patient based on 2 treatment choices and on his clinical and tumor characteristics. Among 4544 men (mean [SD] age, 61.2 [8.0] years), 3769 underwent radical prostatectomy, 775 received external beam radiotherapy, 157 (3.5%) had CF, 90 (2.0%) died after CF, and 378 (8.3%) died of other causes. Across all patients, there was no significant difference in risk of CF for surgery vs radiotherapy (hazard ratio, 0.80; 95% CI, 0.52-1.23). However, using multistate models, in some cases individualized predictions resulted in different expected outcomes between surgery and radiotherapy for a given patient. In this study, after adjustment for measured confounders, the hazard of CF was similar between treatments on average. However, these data indicate a greater oncologic benefit for some individual patients if treated with surgery and for other patients if treated with radiotherapy. Individualized predictions provide a novel approach to facilitate treatment decision making.