Prognostic factors for relapse in patients with clinical stage I testicular non-seminoma: A nationwide, population-based cohort study

Approximately 30% of patients with clinical stage I non-seminoma (CSI-NS) relapse. Current risk stratification is based on lymphovascular invasion (LVI) alone. The extent to which additional tumor characteristics can improve risk prediction remains unclear. To determine the most important prognostic factors for relapse in CSI-NS patients. Population-based cohort study including all patients with CSI-NS diagnosed in Denmark between 2013 and 2018 with follow-up until 2022. Patients were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, histological slides from the orchiectomy specimens were retrieved. Histological slides were reviewed blinded to the clinical outcome. Clinical data were obtained from medical records. The association between prespecified potential prognostic factors and relapse was assessed using Cox regression analysis. Model performance was evaluated by discrimination (Harrell’s C-index) and calibration. Of 453 patients included, 139 patients (30.6%) relapsed during a median follow-up of 6.3 years. Tumor invasion into the hilar soft tissue of the testicular hilum, tumor size, LVI and embryonal carcinoma were independent predictors of relapse. The estimated 5-year risk of relapse ranged from 85%, depending on the number of risk factors. After internal model validation, the model had an overall concordance statistic of 0.75. Model calibration was excellent. The identified prognostic factors provide a much more accurate risk stratification than current clinical practice, potentially aiding clinical decision-making. •Truly unselected population-based cohort of stage I non-seminoma patients•Contemporary centralized pathology review•Four independent predictors of relapse•Risk of relapse ranged from 85% depending on combinations of risk factors•The identified prognostic factors are easily incorporated into clinical practice