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The aim of this short review is to summarize “clinical practice changing” abstracts about genitourinary cancers from this year’s ASCO Annual Meeting. The phase 3 JAVELIN Bladder 100 trial showed astonishing overall survival (OS) data up to 22 months in metastatic urothelial carcinoma (mUC), using a novel gold standard in the first-line setting of mUC—immunotherapy maintenance with avelumab after response to platinum-based chemotherapy. In the first-line treatment of metastatic RCC (mRCC), two phase 2 trials (OMNIVORE and HCRN GU16-260) evaluated the efficacy of a novel sequential strategy, nivolumab monotherapy followed by ipilimumab rescue if nonresponse to nivolumab, confirming that this therapeutic concept is less effective as upfront combination treatment. Finally, updated 24-month progression-free survival (PFS) and OS rates of the KEYNOTE-426 are presented, showing efficacy most in intermediate- and poor-risk patients for the combination pembrolizumab plus axitinib compared with sunitinib. According to the impressive data from the HERO trial, the US Food and Drug Administration granted relugolix priority review as the first oral GNRH receptor antagonist in advanced prostate cancer. Moreover, 18F‑DCFPyL-PET/CT is a promising diagnostic tool for biochemical recurrence as the CONDOR trial confirmed diagnostic superiority of PyL-PET/CT compared with conventional imaging in detecting occult metastasis even in low PSA values. In nonmetastatic castration-resistant prostate cancer (nmCRPC), final OS data of ARAMIS, PROSPER and SPARTAN evaluating efficacy and safety of second-generation antiandrogens versus placebo were presented. In patients with mCRPC progressing after docetaxel, 177Lu-PSMA-617 demonstrated improved rates of 50% reduction in PSA relative to cabazitaxel (TheraP study).