External validation of the European association of urology biochemical recurrence risk groups to predict mortality after radical prostatectomy or radiation therapy in a North American cohort

Objectives: This study aimed to externally validate the European Association of Urology (EAU) biochemical recurrence (BCR) risk stratification in a North American population after radical prostatectomy (RP) and radiation therapy (RT), where validation remains lacking despite prior European and Asian validation. Materials and methods: We identified all patients with BCR after RP or RT between 1995 and 2023 from a North American institutional database and classified them by EAU criteria. Primary outcome was prostate cancer-specific mortality (CSM). We calculated Harrell's concordance indices (C-index) and used competing-risk regression to assess associations between EAU risk groups and CSM, comparing performance to multivariable models including age, clinical stage, Gleason grade, PSA doubling time and time to BCR. Results: Among the 940 patients (646 RP, 294 RT; 40.5% African American), 563 (59.9%) had low-risk and 377 (40.1%) high-risk BCR. The 10-year cumulative incidence of CSM was 3.6% versus 12% for low-risk versus high-risk RP patients and 18.4% versus 49.5% for low-risk versus high-risk RT patients. EAU high-risk BCR was associated with increased CSM in both groups (RP: HR 2.83, 95% CI 1.47–5.46; RT: HR 3.98, 95% CI 2.43–6.53). The EAU classification showed moderate discrimination (Harrell's C-index 0.62 for RP, 0.69 for RT). Multivariable models including clinical variables demonstrated a Harrell's C-index of 0.76 for both RP and RT. Conclusions: This first North American validation confirms moderate EAU discriminative ability. For RP patients, low 10-year CSM in low-risk BCR (3.6%) supports surveillance. However, low-risk RT BCR showed substantial CSM (18.4%), exceeding high-risk RP (12%), suggesting current criteria inadequately stratify risk after RT.