Multi-institutional Development and External Validation of a Machine Learning Model for the Prediction of Distant Metastasis in Patients Treated by Salvage Radiotherapy for Biochemical Failure After Radical Prostatectomy.

ABSTRACT

BACKGROUND: Up to 40% of patients with prostate cancer may develop biochemical recurrence after surgery, with salvage radiation therapy (SRT) being the only curative option. In 2016, Tendulkar et al. (Contemporary update of a multi-institutional predictive nomogram for salvage radiotherapy after radical prostatectomy. J Clin Oncol 2016;343648-54) published a nomogram to predict distant metastasis in a cohort of patients treated with SRT with pre-SRT prostate-specific antigen (PSA) of 0.5 ng/ml after radical prostatectomy. In modern practice, SRT is delivered at lower PSA values. OBJECTIVE: To train and externally validate a machine learning model to predict the risk of distant metastasis at 5 yr in a contemporary cohort of patients receiving SRT. DESIGN, SETTING, AND PARTICIPANTS: We trained a machine learning model on data from 2418 patients treated with SRT at one institution, with a median PSA value of 0.27 ng/ml. External validation was done in 475 patients treated at two different institutions. Patients with cM1, pN1, or pT4 disease were excluded, as were patients with PSA >2 ng/ml or PSA 0, and patients with radiation dose <60 or ≥80 Gy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Model performance was assessed using calibration and time-dependent area under the receiver operating curve (tAUC). RESULTS AND LIMITATIONS: Our model had better calibration and showed improved discrimination (tAUC = 0.72) compared with the Tendulkar model (tAUC = 0.60, p < 0.001). The main limitations of this study are its retrospective design and lack of validation on patients who received hormone therapy. CONCLUSIONS: The updated model can be used to provide more individualized risk assessments to patients treated with SRT at low PSA values, improving decision-making. PATIENT SUMMARY: Up to 40% of patients with prostate cancer may develop biochemical recurrence after surgery, with salvage radiation therapy as the only potentially curative option. We trained and validated a machine learning model using clinical and surgical data to predict a patient's risk of distant metastasis at 5 yr after treatment. Our model outperformed the reference tool and can improve clinical decision-making by providing more personalized risk assessment.