Welcome back to your Saturday PSAWeekly.
This week spans the molecular to the surgical, with one thread throughout: questioning long-held assumptions and asking who truly benefits rather than treating everyone the same.

In this week's brief:

If PSAWeekly has earned a place in your Saturday routine, please refer a colleague at PSAWeekly.com so they never miss a brief.

Let's dive in.

This prospective cohort study examined whether quitting smoking after a bladder cancer diagnosis improves survival a question that prior retrospective work and limited prospective studies had left unresolved. The authors analyzed 169 patients with urothelial bladder cancer (diagnosed 2006–2022) drawn from MD Anderson's Tobacco Research and Treatment Program (TRTP), which offers personalized counseling, behavioral support, and pharmacotherapy at no cost. Self-reported abstinence was recorded at 3, 6, and 9 months after consultation, and outcomes were assessed using landmark analysis with multivariable Cox models.

Cohort: The group was predominantly White (87.6%) and male (74.6%), with a median age of 60 and a heavy smoking history (median 50 pack-years). Both muscle-invasive and non–muscle-invasive disease were represented, and 94% received guideline-concordant cancer care.

Key findings: Abstinence rates were 43%, 44%, and 38% at 3, 6, and 9 months. After a median follow-up of 5.7 years, quitting was independently associated with markedly better survival:

The OS benefit held regardless of tumor stage and appeared somewhat stronger in muscle-invasive disease. Sensitivity analyses adjusting for comorbidity and imputing missing data confirmed the association.

Limitations: The cohort was small and demographically narrow (limiting generalizability), the nonabstinent group had more metastatic disease at baseline (possible confounding favoring abstinence), abstinence was self-reported and measured by point-prevalence (possibly overstating sustained cessation), and cause of death was unknown for 12% of patients.

Conclusion: A structured smoking cessation program after bladder cancer diagnosis produced relatively high abstinence rates and was linked to better overall, cancer-specific, and recurrence-free survival across all disease stages. The authors argue that proactive, patient-centered tobacco cessation should be a routine, integrated component of bladder cancer care.

This study analyzed who prescribes testosterone replacement therapy (TRT) and in what form, using Medicare Part D prescriber data from July 2017 through June 2024. With an expanding range of prescribers including primary care providers and advanced practice providers (APPs) and newer formulations such as oral testosterone undecanoate (TU, approved 2019), the authors set out to map recent prescribing patterns by specialty and route of administration to better guide education and guideline efforts.

Methods: The team extracted all claims containing "testosterone" from the CMS Medicare Part D Prescribers database and grouped prescribers into urology, APPs, internal medicine subspecialties, family medicine, endocrinology, and other. Because APPs were not tied to a specialty in the database, they were analyzed separately, with top prescribers' affiliations identified through manual online searches. Claims were also classified by route (topical, injectable, oral, buccal, pellet).

Key findings:

Discussion points: The authors attribute the broader surge partly to the 2023 TRAVERSE trial, which eased cardiovascular and prostate cancer safety concerns, alongside pandemic-driven telehealth expansion and the growth of APP-led clinics. The injectable preference likely reflects lower cost, predictable levels, and no transference risk features emphasized in 2018 AUA/Endocrine Society guidelines that may explain the drop in topical use.

Limitations: Medicare Part D data exclude other insurers, uninsured patients, and direct-to-consumer, compounding, or medical-tourism sources; APP affiliations relied on manual searches; some claims lacked formulation detail; and the absence of patient-level data prevents any judgment about prescribing appropriateness.

Conclusion: TRT prescribing has expanded substantially and increasingly involves a diverse set of providers, especially APPs. The authors stress engaging this wider prescriber base in guideline dissemination to ensure appropriate counseling and access for hypogonadal men.

This large statewide cohort study tested a widely held assumption in stone surgery that using a ureteral access sheath (UAS) during ureteroscopy (URS) for renal stones reduces infectious complications by lowering intrarenal pressure. Although this belief underpins much of clinical practice (and even informs EAU guidance), the supporting evidence has been weak and inconsistent. The authors used the Michigan Urological Surgery Improvement Collaborative (MUSIC) ROCKS registry to examine real-world practice patterns and outcomes.

Methods: They analyzed 6,142 adults who underwent single-stage unilateral URS for renal stones across 34 Michigan practices (June 2016–October 2022). The primary outcome was infection-related hospitalization (for fever, UTI, or sepsis) within 30 days. Multivariable logistic regression adjusted for comorbidity, recurrent UTI history, stone size, preoperative urine testing, stenting, and other clinical factors.

Key findings:

Notably, the authors re-examined the single influential prior study (Traxer et al., 2015) that reported a protective effect and argue its complication percentages reflected proportion-of-complications rather than incidence among patients at risk; recalculating gave no significant sepsis difference.

Limitations: The observational design allows residual confounding; events may be missed if patients sought care outside participating systems; and key operative details (irrigation pressure, operative time, sheath size, failed placements) were not captured. Findings reflect Michigan practice and may not generalize.

Conclusion: UAS use should not be assumed to protect against infection or sepsis after ureteroscopy for renal stones. Infection risk is driven mainly by patient factors, which should guide counseling, risk stratification, and perioperative planning. The authors call for prospective randomized trials—incorporating intrarenal pressure measurement—to clarify the issue.

This single-center retrospective study offered the first head-to-head comparison of three imaging modalities microultrasound (microUS), multiparametric MRI (mpMRI), and PSMA PET/CT for detecting clinically significant prostate cancer (csPCa) and extraprostatic extension (EPE), using whole-mount histopathology (WMHP) from radical prostatectomy specimens as the gold-standard reference. WMHP is more rigorous than the biopsy pathology used in most prior comparisons because it maps the entire tumor and its margins rather than sampled cores.

Methods: The authors studied 68 men with intermediate- or high-risk prostate cancer who underwent microUS and mpMRI before robot-assisted radical prostatectomy (January 2023–October 2024); 44 also had PSMA PET/CT. Blinded readers scored lesions using PRI-MUS, PI-RADS v2.1, and PRIMARY systems, and imaging was correlated with WMHP at both the lesion and sector level. Detection rates, positive predictive values (PPVs), and ROC curves (AUCs) were compared statistically.

Key findings:

Limitations: The single-center, retrospective design, small csPCa-enriched surgical cohort (which prevented assessing specificity and negative predictive value), reliance on a highly experienced microUS reader (an operator-dependent modality), and non-random PSMA PET/CT subgroup all limit generalizability.

Conclusion: MicroUS performed comparably to mpMRI and PSMA PET/CT for detecting significant and index prostate cancer lesions, supporting its use as an accessible, office-based complement particularly where MRI is unavailable or contraindicated. mpMRI nonetheless remains superior for local staging and EPE assessment and should stay central to surgical planning. The missed anterior, small-volume lesions underscore the continued need for systematic anterior sampling when imaging is negative but clinical suspicion persists.

This study used the large-scale Adolescent Brain Cognitive Development (ABCD) dataset to investigate the brain-based mechanisms underlying nocturnal enuresis (NE, or bedwetting), a common neurodevelopmental condition whose neural basis has remained poorly understood. The authors examined both children with ongoing symptoms and those who had outgrown bedwetting, aiming to identify structural and functional brain features tied to active symptoms versus their resolution.

Methods: Working with cross-sectional data from 3,472 children aged 9–10, the researchers sorted participants into three groups: active nocturnal enuresis (ANE, n=225), past history of nocturnal enuresis now resolved (HNE, n=1,171), and healthy controls (n=2,076). A multimodal neuroimaging approach assessed brain macrostructure (structural MRI), white matter microstructural integrity (diffusion MRI), and functional connectivity (resting-state fMRI). Group comparisons used linear models in an ANCOVA framework, adjusting for intracranial volume and handedness, with False Discovery Rate correction.

Key findings:

Conclusion: Nocturnal enuresis appears linked to complex deficits in central signaling. The reduced cingulo-opercular network connectivity seen in both current and former bedwetters points to a possible impairment in processing internal homeostatic bladder signals during sleep a trait that may persist even after symptoms resolve, while structural changes in the resolved group may reflect the brain maturation underlying recovery.

This randomized controlled trial examined whether giving ketorolac a non-steroidal anti-inflammatory drug (NSAID) before circumcision reduces postoperative pain in children. Pain is the most frequent complaint after this common procedure, and poorly controlled pain can worsen recovery and lower satisfaction for both patients and parents. The authors set out to test ketorolac's effect, since it offers analgesia but has often been avoided over bleeding concerns.

Methods: The team ran a prospective, single-blinded trial at one tertiary children's hospital. Boys aged 1–17 undergoing circumcision were randomized to receive either intravenous ketorolac (0.5 mg/kg, capped at 30 mg) or a normal saline placebo before surgery. The primary outcome was parental perception of pain at 24 hours, measured with the validated Parents' Postoperative Pain Measure (PPPM). Secondary outcomes included recovery-room pain scores, bleeding, vomiting, and analgesic use, with reporting following CONSORT standards.

Results: Of 100 participants (50 per group), the mean 24-hour PPPM score was 6.1 with saline versus 5.5 with ketorolac a non-significant difference (mean difference −0.55; 95% CI −1.9 to 0.83; p = 0.43). In the recovery unit, ketorolac showed no significant effect on the FLACC (Face, Legs, Activity, Cry, Consolability) score, but did produce a modest, statistically significant reduction on the numerical rating scale (−1.2 points; 95% CI −2.2 to −0.18; p = 0.026).

Discussion and conclusion: Pre-operative IV ketorolac did not lower parent-reported pain at 24 hours compared with placebo. The slightly lower immediate postoperative pain seen with ketorolac in exploratory analysis was likely too small to be clinically meaningful. The authors note that, despite longstanding caution about NSAID-related bleeding, robust evidence supporting that concern is lacking. They highlight this as the first study to evaluate ketorolac specifically in pediatric circumcision, while acknowledging that the PPPM, though family-centered, is an indirect gauge of a child's pain.

[email protected]