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¹Department of Radiation Oncology, Başkent University Faculty of Medicine, Ankara-Türkiye
²Radiation Oncology Unit, İskenderun Gelisim Hospital, Hatay-Türkiye
³Department of Radiation Oncology, Başkent University Faculty of Medicine, Adana Dr. Turgut Noyan Research and Treatment Center, Adana-Türkiye DOI : 10.5505/tjo.2025.7 The use of Stereotactic Ablative Radiotherapy (SABR) in the treatment of genitourinary system cancers has increased, supported by studies showing a survival benefit, particularly in oligometastatic disease. However, as an increasing number of patients receive novel systemic therapies concurrently, the toxic effects of these interactions require careful evaluation. This review aims to examine the efficacy and toxicity outcomes of combining radiotherapy (especially SABR) with novel systemic agents in Prostate, Bladder, and Renal Cell Cancers (RCC), based on current evidence and the EORTC-ESTRO OligoCare consortium guidelines. Systemic Agent Risk Categorization: Combining SABR with systemic therapy classified as high-risk when showed a significant increase in Grade ?3 toxicity, whereas no such increase was observed with low-risk agents. Prostate Cancer (PCa): New-generation hormonal agents (Abiraterone, Enzalutamide, Apalutamide) can be used safely concurrently with radiotherapy. Applying SABR to oligoprogressive lesions in Metastatic Castration Resistant PCa (mCRPC) can extend the duration of the current hormonal treatment duration. Bladder Cancer (BCa): The use of immunotherapy and Antibody-Drug Conjugates is increasing, with nearly all of these agents falling into the high-risk drug category. Evidence in this area is low, and experience is limited. A 1 to 2 week break between RT and systemic treatment is recommended to mitigate toxicity risk. RCC: TKIs and immunotherapies are widely used and are mostly in the high-risk drug category. Despite this, SABR (with immunotherapy or TKI) in oligoprogressive RCC lesions has shown good tolerability with high local control rates (over 90% 2-year LC) and can extend the time before switching systemic therapy (NEST) by a median of 12.6 to 15.2 months. A 1 to 2 week break between RT and systemic treatment is recommended to mitigate toxicity risk. The combination of RT and novel systemic agents in genitourinary system cancers is promising in terms of efficacy and prolonging the time to switch systemic therapy, especially in oligometastatic disease. As agents other than those for prostate cancer are often high-risk, careful consideration of optimal treatment timing and individualized decisions made through a multidisciplinary approach are vital. Keywords : Bladder cancer; oligometastasis; prostate cancer; renal cell carcinoma; SABR; systemic therapy; toxicity