Using ctDNA to Inform Adjuvant Therapy for Urologic Malignancies

Decisions regarding the use of adjuvant systemic therapy in genitourinary (GU) malignancies-including bladder, kidney, and prostate cancers-are currently driven by clinicopathologic risk factors, which incompletely capture individual risk of residual disease. Consequently, patient selection for adjuvant treatment remains imprecise, leading to both overtreatment of cancers unlikely to recur and undertreatment of those with occult residual disease. Circulating tumor DNA (ctDNA), a minimally invasive liquid biopsy biomarker for minimal residual disease, has emerged as a promising tool to refine adjuvant treatment decision-making. Detection of ctDNA reflects persistent tumor-derived genomic material and often precedes radiographic recurrence, whereas ctDNA negativity is consistently associated with favorable oncologic outcomes. In this review, we summarize the evolving evidence supporting the use of ctDNA to guide adjuvant therapy decisions in bladder, kidney, and prostate cancers. This is not a comprehensive review on all of the potential applications of ctDNA in these malignancies. Rather, we aim to highlight disease-specific, adjuvant-guiding applications, including post-neoadjuvant and post-cystectomy decision-making in bladder cancer and emerging proof-of-concept data in renal cell carcinoma, and explore the potential application of ctDNA in the post-prostatectomy setting. Collectively, these data suggest that ctDNA may enable a paradigm shift toward biologically informed escalation and de-escalation of adjuvant therapy across GU malignancies, while underscoring the need for prospective validation in biomarker-driven clinical trials.