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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.

Overall survival was 78.9% in the combination group compared with 69.5% in the leuprolide-alone group (HR 0.60). Enzalutamide monotherapy resulted in an overall survival of 73.1%, which was not statistically significant. We were already aware of the progression-free survival benefit; now we have overall survival data. This case was also presented in the MOC questions, where the correct answer was to add enzalutamide for a patient with a rising PSA on an LHRH agonist without imaging evidence of disease.

Metformin did not significantly reduce the risk of disease progression compared with active surveillance in patients with low-risk prostate cancer.

For our radiation oncology colleagues, the addition of PSMA-directed therapy prior to stereotactic body radiation therapy (SBRT) improved progression-free survival (PFS) in patients with oligometastatic prostate cancer. Two cycles of PSMA-directed therapy were administered before SBRT.

A new MMAI-derived digital pathology biomarker was trained and prospectively validated across multiple NRG/RTOG phase III trials, including RTOG 9202 (N=1,192), to predict which high-risk/locally advanced PCa patients benefit from LT-ADT vs ST-ADT with RT. In the overall cohort, LT-ADT reduced DM (17% vs 26% at 15 years) and DDM (15% vs 23% at 15 years), but this benefit was limited to biomarker-positive patients (DM: 19% vs 33%; DDM: 19% vs 30%), with no advantage seen in biomarker-negative patients (DM: 11% vs 11%; DDM: 9% vs 10%). This tool could allow about a third of our "high-risk" patients to avoid two extra years of ADT without compromising metastasis outcomes, while ensuring we intensify for those most likely to benefit. In short, this is a practical step toward personalizing ADT duration and sparing toxicity for a significant subset of our patients.

A 13% reduction in mortality was observed in the screening group, with an improved harm-benefit ratio. For every 456 men screened, one prostate cancer death was prevented. It is an easy and inexpensive test, though concerns remain regarding unnecessary biopsies and overtreatment.

Pasritamig was administered to patients who had received a median of four prior lines of systemic therapy. It was well tolerated, with manageable adverse events, making it suitable for outpatient administration. The treatment showed a median radiographic progression-free survival of 7.85 months, and 14 out of 33 participants achieved a ≥50% reduction in baseline PSA levels. So, stay tuned.

In patients with localized prostate cancer, predominantly low-risk and intermediate-risk disease, the long-term update reveals 13-year outcomes. Treatment failure occurred less frequently in men undergoing HIMRT (n = 13) compared with those undergoing CIMRT.