Despite three randomized trials indicating a significant reduction in biochemical recurrence (BCR) in high-risk patients, adjuvant radiotherapy (aRT) was rarely performed, even in patients harboring high-risk features. aRT is associated with a higher risk of urinary incontinence and is often criticized for the lack of patient selection criteria. With a BCR rate reaching 30-70% in high-risk patients, a consensus between urologists and radiation oncologists was needed, leading to three different randomized trials challenging aRT with early salvage radiotherapy (eSRT). In these three different randomized trials with event-free survival as the primary outcome and a planned meta-analysis, eSRT appeared as non-inferior to aRT, answering, for some, this never-ending question. For many, however, the debate persists; these results raised several questions among urologists and radiation oncologists. BCR is thought to be a surrogate for clinically meaningful endpoints such as overall survival and cancer-specific survival but may be poorly efficient in comparison with metastasis-free survival. Imaging of rising prostate-specific antigen (PSA), post-operative persistent PSA and BCR was revolutionized by the broader use of MRI and nuclear imaging such as PET-PSMA; these imaging modalities were not analyzed in the previous randomized trials. A sub-group of very high-risk patients could possibly benefit from an adjuvant radiotherapy; but their usual risk factors such as high Gleason score or invaded surgical margins mean they are unable to be selected. More precise biomarkers of early BCR or even metastatic-relapse were developed in this setting and could be useful for the patients' stratification. In this review, we insist on the need for multidisciplinary discussions to fully comprehend the individual characteristics of each patient and propose the best treatment strategy for every patient.
Keywords: adjuvant radiotherapy; biomarker; early salvage radiotherapy; personalized medicine.