Adjuvant or Salvage Radiation Therapy for Prostate Cancer after Prostatectomy: Current Status, Controversies and Perspectives

SIMPLE SUMMARY: The management of patients with biochemical recurrence after prostatectomy has undergone significant changes in recent years. Currently, close monitoring of prostate-specific antigen (PSA) with early salvage radiotherapy (RT) in case of recurrence is the standard of care based on several randomized trials and a meta-analysis that has demonstrated its non-inferiority to adjuvant RT. Uncertainties remain regarding the management of patients at very high risk of recurrence, including appropriate selection criteria for adjuvant hormone therapy, and the role of imaging in refining the treatment strategy. This review explains this paradigm shift, raises points of controversy, and suggests ways to think about the future. ABSTRACT: Nearly one-third of the patients who undergo prostatectomy for prostate cancer have a biochemical recurrence (BCR) during follow-up. While several randomized trials have shown that adjuvant radiation therapy (aRT) improves biochemical control, this strategy has not been widely used because of the risk of toxicity and the fear of overtreating patients who would not have relapsed. In addition, the possibility of close PSA monitoring in the era of ultrasensitive assays enables to anticipate early salvage strategies (sRT). Three recent randomized trials and their meta-analysis have confirmed that aRT does not improve event-free survival compared to sRT, imposing the latter as the new standard of treatment. The addition of androgen deprivation therapy (ADT) to RT has been shown to improve biochemical control and metastasis-free survival, but the precise definition of to whom it should be proposed is still a matter of debate. The development of genomic tests or the use of artificial intelligence will allow more individualized treatment in the future. Therapeutic intensification with the combination of new-generation hormone therapy and RT is under study. Finally, the growing importance of metabolic imaging (PET/CT) due to its performance especially for low PSA levels will help in further personalizing management strategies.