Welcome back to your Saturday PSAWeekly. It’s good to be back in your inbox.

We return after a short pause with a theme that suits a comeback: moving the line. In this issue, established treatments are being tested in settings they weren’t originally designed for. A PARP inhibitor combination used in castration-resistant disease now has FDA approval at the start of metastatic hormone-sensitive prostate cancer. Bipolar enucleation, long the preferred option for large glands, is tested head-to-head against TURP in moderate-sized prostates. And alpha-blockers, standard after SWL in adults, are pooled in the first meta-analysis focused on children. Elsewhere, a national birth cohort looks at everyday household sprays during pregnancy, and real-world data asks what the GLP-1 boom means for the stone clinic. The same question runs through all of it: when a treatment moves into new territory, does the evidence support it?

This week’s issue covers:

Thank you for staying with us. Let’s get into it.

On October 26, 2026, the FDA approved talazoparib (Talzenna®) plus enzalutamide for metastatic castration-sensitive prostate cancer with homologous recombination repair (HRR) gene alterations, which the FDA label now calls “mAPMN/S.” The combination was previously approved only for metastatic castration-resistant disease.

In TALAPRO-3, 599 patients on ADT were randomized to enzalutamide plus talazoparib or placebo. The combination cut the risk of radiographic progression or death by 52% (HR 0.48; 95% CI 0.36–0.65). Median rPFS was not reached, versus 45.8 months with enzalutamide alone. The main toxicity was grade ≥3 anemia (51% vs 3%).

Bottom line for practice: HRR testing at diagnosis of metastatic hormone-sensitive disease now changes treatment. Monitor blood counts closely.

Limitations: overall survival data are still immature, and the control arm did not include docetaxel.

Endoscopic enucleation is the preferred approach for large prostates, but for moderate-sized glands TURP remains the standard. This two-center randomized noninferiority trial asked whether bipolar enucleation of the prostate (BipolEP), which uses a dedicated button electrode for blunt dissection, can replace TURP in this size range. The comparator arm was bipolar TURP.

Eighty-four men with prostate volumes of 40–150 ml, IPSS ≥15, and either Qmax ≤15 ml/s or urinary retention were randomized 1:1. The primary endpoint was IPSS at 12 months, with a noninferiority margin of 3 points.

At one year, both groups reached a median IPSS of 5, with an estimated difference of 0 points (90% CI –2 to 1), confirming noninferiority. BipolEP took longer (86 vs 67 min) but removed more tissue (38.4 vs 25.0 g) and was slightly more efficient (0.5 vs 0.4 g/min). Complication patterns differed early: minor 30-day complications (Clavien-Dindo 1–2) were more common after BipolEP (54% vs 28%), while major complications (CD ≥3) occurred only after TURP (10%). From 1 to 12 months, complication rates were similar.

Bottom line for practice: In moderate-sized prostates, bipolar enucleation offers the same one-year symptom relief as TURP with more complete tissue removal and no major early complications. It’s a reasonable alternative for surgeons trained in enucleation, though the procedure takes longer.

Limitations: follow-up was only 12 months, which is too short to compare retreatment rates (enucleation’s main expected advantage). The trial was also small and open-label, and only 79% of patients were included in the per-protocol analysis.

Congenital anomalies of the urinary tract are the main cause of end-stage kidney disease in children. Many households use sprays such as waterproofing agents and insect repellents, and their safety during pregnancy is uncertain. Researchers from the Japan Environment and Children’s Study (JECS), a national birth cohort, examined whether these exposures were linked to urological anomalies in children up to 2 years of age.

The analysis covered 80,658 mother–child pairs. Mothers reported their use of waterproofing, insect-repellent, and insecticide sprays on questionnaires during pregnancy. Physician-diagnosed anomalies were grouped into VUR, hydronephrosis, hypospadias, cryptorchidism, and other anomalies, and the models adjusted for maternal and neonatal factors.

There were 1,078 anomalies in total, about 13 per 1,000 births, mostly in boys. In boys, maternal use of waterproofing and insect-repellent sprays was associated with roughly a 30% higher likelihood of urological anomalies in both the first and second year of life (adjusted OR 1.34 and 1.31). Waterproofing spray was specifically associated with VUR in boys. In girls, insecticide spray use was linked to hydronephrosis in the first year (adjusted OR 2.15).

Bottom line for practice: This is an association, not proof of cause. It does support simple, practical advice: when counseling pregnant patients, suggest limiting unnecessary chemical spray use during pregnancy.

Limitations: the study is observational, with self-reported exposure and no measurement of specific chemicals. Effect sizes are modest, with some confidence intervals touching 1.0, and testing many subgroups raises the chance of findings occurring by chance. The authors themselves call for mechanistic and longitudinal studies.

Shockwave lithotripsy (SWL) is the main non-invasive treatment for upper tract stones in children, but clearing the fragments afterwards remains a problem. AUA and EAU guidelines support alpha-blockers after SWL in adults, but the evidence in children has been unclear, and no previous meta-analysis had focused only on this pediatric setting.

The authors performed a systematic review and meta-analysis of randomized trials published up to March 2026. They searched four major databases and included children aged 18 or younger treated with tamsulosin or silodosin after primary SWL. Risk of bias was assessed with Cochrane RoB 2, certainty of evidence was graded with GRADE, and the protocol was registered in advance with PROSPERO.

Four RCTs with 408 children met the criteria. Alpha-blockers increased the stone-free rate after a single session by about 16% (RR 1.16; 95% CI 1.04–1.29), with very little variation between trials. They also shortened the time to fragment passage by an average of 2.4 days. Pain scores and analgesic use were consistently lower with treatment. Fewer children on treatment needed additional procedures (RR 0.68), but this difference was not statistically significant, because there were few such events overall. Side effects were more common with treatment, but all were mild and short-lived, and no child stopped the medication.

Bottom line for practice: After successful fragmentation, an alpha-blocker is a reasonable option to speed stone clearance and reduce pain in children. Discuss with families that its use in children is usually off-label.

Limitations: only four small trials were included, and the confidence interval for side effects is wide (OR 7.68; 95% CI 1.22–48.42). The authors recommend larger multicenter RCTs before this becomes guideline-level practice.

GLP-1 receptor agonists have moved far beyond diabetes care. Use among adults without diabetes rose about sevenfold between 2019 and 2023, and by 2024 more than one in eight American adults had used one. Urologists have disagreed about what this means for stones. One view is that better metabolic control should lower stone risk. The other is that rapid weight loss, dehydration and muscle breakdown could raise it.

A team from the Cleveland Clinic’s Glickman Urological & Kidney Institute investigated this using TriNetX, a large multi-institutional US database. They compared new stone events in patients prescribed GLP-1 agonists with those who were not, in two groups: patients with diabetes, and non-diabetic patients with obesity using the drugs for weight loss. Each group was analyzed separately for patients with and without a previous stone history, with propensity matching to balance the groups.

The results consistently favored GLP-1 agonist use:

The authors conclude that GLP-1 agonists may protect against stones, but they say it’s too early to prescribe them for this purpose, and prospective trials are needed.

Bottom line for practice: There’s no evidence yet to prescribe GLP-1 agonists for stone prevention. The data are reassuring for your stone patients already taking them, though: the concern that rapid weight loss drives stone formation isn’t supported here.

Limitations: this is a retrospective claims-database analysis, with no data on stone composition, imaging confirmation or 24-hour urine chemistry. Residual confounding is likely, since patients prescribed GLP-1 agonists may differ in access to care and health behaviors. After matching, the benefit in recurrent stone formers was small.

With so many patients now on these drugs, three points are worth keeping in mind:

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