Prostate cancer is the most common cancer in men in 118 countries.1 Recently, the Lancet Commission on prostate cancer reported a projection that the number of new cases annually will rise from 1.4 million in 2020 to 2.9 million by 2040.2 Radiotherapy (RT) is a well-established treatment for patients with prostate cancer, both in the primary setting and for disease relapse after initial therapy. In the metastatic setting, RT has long been used to palliate prostate cancer-associated symptoms, but emerging evidence now suggests that RT can prolong time to disease progression, delay the onset of serious genitourinary events, and potentially improve survival when combined with systemic therapy in appropriately selected patients.3, 4, 5, 6

With recent advancements in biomarker discovery, RT delivery, medical imaging and systemic therapies, the management of prostate cancer has become increasingly complex, particularly for localized high-risk disease.7 This evolving landscape necessitates close collaboration among multidisciplinary teams of specialized experts. Accordingly, the objective of this Issue is to provide a comprehensive overview of the role of RT within the multidisciplinary treatment setting for prostate cancer, with a special focus on high-risk disease and other challenging scenarios where RT plays a critical role (such as those with biochemically recurrent, lymph node-positive, oligometastatic, and radiorecurrent disease). We invited a panel of internationally recognized prostate cancer experts to contribute 18 articles addressing critical aspects of contemporary management strategies for high-risk prostate cancer, which are summarized below.