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An important post-hoc analysis from ARCHES and PROSPER that quantifies something we've suspected clinically, roughly 1 in 4 enzalutamide-treated patients who progress radiographically have no prostate-specific antigen (PSA) rise, and the majority won't meet PCWG2/3 PSA progression criteria. Liver metastases were 5-fold more common at radiographic progression on enzalutamide versus control, suggesting lineage plasticity and AR-independent clones are the culprit. Bottom line for practice: don't wait for PSA to rise before imaging your metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC) patients on ARPIs, periodic cross-sectional imaging, especially in the first two years, is warranted regardless of PSA trend.

Solid pragmatic phase II showing oxybutynin 2.5mg and 5mg BID (twice a day) both beat placebo for hot flash reduction in men on androgen-deprivation therapy (ADT), with no serious toxicities beyond expected dry mouth. Given that venlafaxine failed in this population and megestrol/medroxyprogesterone carry real concerns, this gives us an evidence-based option we can feel good about reaching for, especially in patients who also have urinary symptoms. Neurokinin B (NKB) antagonists are coming but not yet studied here, so oxybutynin fills a real gap now.

Moving PARP inhibition earlier into the hormone-sensitive androgen pathway modulation–sensitive (APMS) setting, this trial shows talazoparib plus enzalutamide cuts the risk of progression or death in half (HR 0.48) in HRR-altered metastatic prostate cancer, with an impressive 3-year progression-free survival (PFS) of 77% versus 56%. The benefit extends beyond BRCA1/2 to ATM and CDK12 as well, which is clinically meaningful given that two-thirds of this population was non-BRCA.