Lutetium-PSMA moves earlier: a survival-pathway win in hormone-sensitive prostate cancer

The edition in brief

Radioligand therapy is moving up the prostate cancer pathway. In the phase 3 PSMAddition trial, 1,144 men with PSMA-positive metastatic hormone-sensitive prostate cancer were randomised to standard androgen deprivation plus an androgen-receptor pathway inhibitor, with or without 177Lu-PSMA-617. Adding the radioligand improved radiographic progression-free survival (hazard ratio 0.72, 95% CI 0.58 to 0.90; p=0.0021). Grade 3 or worse adverse events were more common (51% versus 43%) and dry mouth affected nearly half, but there were no unexpected safety signals. This brings a treatment previously reserved for late castration-resistant disease into the hormone-sensitive setting, and is likely to reshape practice as access allows. In localised high-risk disease, the GETUG-AFU 18 trial found dose-escalated radiotherapy (80 Gy versus 70 Gy) with long-term androgen deprivation improved 10-year progression-free survival from 72.2% to 83.6% (hazard ratio 0.56, 95% CI 0.40 to 0.78) without more late toxicity. For overactive bladder, a network meta-analysis of five trials and 5,317 patients ranked vibegron best for urgency-incontinence episodes and voided volume, and mirabegron best for daytime frequency and least likely to raise blood pressure. This lands the same week the FDA logged a Class II recall of mirabegron extended-release tablets for a nitrosamine impurity. And a small randomised trial found adding tolterodine to tamsulosin raised distal ureteric stone expulsion from 67% to 83%.