Welcome back to your Saturday PSAWeekly.
This week spans the molecular to the surgical, with one thread throughout: refining how we select, measure, and treat rather than simply doing more of the same.

In this week's brief:

New: We're now on X at @PSAWeekly, posting challenging clinical cases throughout the week to sharpen diagnostic reasoning. Follow along and test your thinking against colleagues.

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Let's dive in.

This review examines the idea that prostate fibrosis may be an underrecognized driver of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). While current medical treatment for LUTS/BPH mainly focuses on reducing prostate enlargement with 5-alpha reductase inhibitors or relaxing smooth muscle with alpha-blockers, the authors argue that these approaches do not address fibrotic remodeling of the prostate. This may help explain why some patients continue to progress despite combination therapy.

The article describes fibrosis as a process driven by chronic inflammation, activation of fibroblasts, transformation into myofibroblasts, and excess deposition of collagen and extracellular matrix, especially in the periurethral and transition zones of the prostate. These structural changes can increase tissue stiffness and reduce urethral compliance, contributing to urinary symptoms even when prostate size alone does not fully explain obstruction. Evidence from both animal studies and human clinical data supports a link between fibrosis, worsening LUTS, and disease progression.

The authors review several potential antifibrotic therapies that could someday be repurposed or adapted for LUTS/BPH. These include established antifibrotic agents such as pirfenidone and nintedanib, as well as other medications with possible antifibrotic effects, including PDE5 inhibitors, pentoxifylline, collagenase Clostridium histolyticum, thalidomide analogues, losartan, and halofuginone. Some of these drugs have shown encouraging findings in preclinical models or early related studies, but none are currently approved specifically for prostate fibrosis, and safety, dosing, and delivery methods remain uncertain.

An important challenge highlighted in the review is how to identify the right patients. Because fibrosis is not routinely assessed in men with LUTS/BPH, the authors discuss the need for better diagnostic strategies. Although histology remains the reference standard, it is not practical for routine use. As a result, noninvasive imaging methods such as shear-wave elastography and magnetic resonance elastography are presented as promising tools for detecting prostate stiffness and potentially selecting men who may benefit from future antifibrotic treatment.

Overall, the review proposes that targeting fibrosis could become a new therapeutic direction in LUTS/BPH, particularly for men who do not respond adequately to current therapies. However, the field is still in an early stage, and more translational and clinical research is needed before antifibrotic treatment can become part of standard practice.

This article summarizes the 2026 European Association of Urology (EAU) Sexual and Reproductive Health Guidelines on the biochemical diagnosis of male hypogonadism. The authors focus on how testosterone should be measured in clinical practice and address ongoing uncertainties about preanalytical conditions, assay choice, and the role of free testosterone and sex hormone–binding globulin (SHBG).

A major message of the paper is that testosterone testing must be standardized to avoid misdiagnosis. The guideline recommends measuring total testosterone in the morning, specifically between 7:00 and 10:00 AM, and in the fasting state. This update narrows the previous upper time limit from 11:00 AM to 10:00 AM, based on evidence showing that testosterone levels follow a circadian rhythm and can also fall significantly after food or glucose intake. The authors also note that for night-shift workers, sampling should be timed according to sleep rather than clock time.

The paper confirms that total testosterone remains the main laboratory test for diagnosing male hypogonadism. A total testosterone level of 12 nmol/L or lower is maintained as a practical threshold for diagnosing symptomatic late-onset hypogonadism when interpreted together with relevant clinical symptoms. The authors emphasize that laboratory variability remains a challenge, particularly because reference ranges differ across assays, so clinicians should work closely with laboratories and favor standardized, validated methods whenever possible.

The article also explains that free testosterone and SHBG can improve diagnostic accuracy in selected patients, especially when SHBG levels are abnormal. This is relevant in conditions such as obesity, insulin resistance, thyroid disease, liver disease, aging, and use of certain medications, all of which can alter SHBG concentrations and distort the interpretation of total testosterone alone. In such cases, the guidelines support measuring SHBG and using calculated free testosterone, rather than relying on direct immunoassays for free testosterone, which are considered unreliable. The Vermeulen formula is identified as the preferred approach for free testosterone calculation.

Overall, the article reinforces that the diagnosis of male hypogonadism should never rely on laboratory numbers alone. Instead, it should combine symptoms, careful sampling conditions, reliable testosterone measurement, and targeted use of SHBG and calculated free testosterone when appropriate. The authors also suggest that emerging evidence may support broader use of SHBG and calculated free testosterone in the future, although stronger data are still needed.

This study examined whether the extent of pelvic lymph node dissection (PLND) during partial cystectomy (PC) influences cancer-specific mortality in patients with bladder cancer. Using data from the SEER database (2004–2021), the authors analyzed 1017 patients who underwent partial cystectomy with lymph node dissection and compared outcomes according to whether patients met commonly accepted eligibility criteria for partial cystectomy: tumor stage ≤T2\leq T2≤T2, tumor size ≤3\leq 3≤3 cm, and a location suitable for segmental resection.

The analysis showed that only a small minority of patients met all three criteria for ideal partial cystectomy candidacy. Specifically, about 19% were classified as eligible, while more than 80% did not fully meet guideline-based criteria. Despite this difference in patient selection, the median number of lymph nodes removed was fairly similar between the eligible and ineligible groups. Over time, however, the average number of removed lymph nodes increased, suggesting that surgeons have been performing more extensive dissections in recent years.

In the overall cohort, removing a greater number of lymph nodes was associated with lower cancer-specific mortality. A similar pattern was observed in patients who were not ideal candidates for partial cystectomy, where a broader lymph node dissection remained independently linked to better cancer-specific outcomes. This suggests that a more extensive PLND may contribute meaningful oncologic benefit in higher-risk or less selected patients undergoing partial cystectomy.

By contrast, among patients who did meet all ideal eligibility criteria for partial cystectomy, the same association did not reach statistical significance. Although the trend still suggested lower mortality with higher lymph node counts, the smaller size of this subgroup may have limited the ability to detect a clear independent effect. It is also possible that the benefit of broader dissection is less pronounced in patients with more favorable disease characteristics.

Overall, the study suggests that more extensive pelvic lymph node dissection during partial cystectomy may improve cancer-specific survival, particularly in patients with less favorable disease features. At the same time, the findings highlight a gap between guideline recommendations and real-world practice, since most patients receiving partial cystectomy in this dataset did not strictly meet ideal selection criteria. The authors conclude that better standardization of both patient selection and lymph node dissection practices may help optimize outcomes.

This multicenter study investigated whether neoadjuvant hormonal therapy (NHT) given before robot-assisted radical prostatectomy (RARP) affects recovery of urinary continence in men with localized prostate cancer. The researchers analyzed patients treated at four hospitals in China and compared those who received NHT followed by surgery with those who underwent surgery alone. To reduce bias between the groups, they used propensity score matching, creating two comparable groups of 249 patients each.

The main finding was that patients who received NHT regained urinary continence faster and more often in the early recovery period than patients who had surgery alone. The median time to continence recovery was 8 weeks in the NHT group compared with 16 weeks in the control group. Short-term continence rates were also clearly better with NHT. In statistical analyses, NHT and younger age were the only independent predictors of faster continence recovery.

The authors suggest that NHT may improve continence recovery by changing prostate anatomy before surgery. In particular, they found evidence that patients treated with NHT tended to have a longer membranous urethral length, which has been linked in previous research to better continence outcomes after prostatectomy. NHT may also reduce prostate volume and improve the surgical field, which could make the operation technically easier and help preserve structures important for continence.

The study also compared different hormonal regimens within the NHT group. Patients receiving stronger androgen receptor inhibitors did not show a statistically significant continence advantage over those receiving first-generation antiandrogens, although there was a slight numerical trend favoring the stronger agents in immediate recovery. Because those subgroups were small, the authors caution that larger studies are needed before firm conclusions can be made.

Despite the promising results, the paper has important limitations. It was not a randomized trial, all patients were from Asian centers, and continence was assessed mainly through patient-reported measures rather than objective functional testing. The matching process also reduced the sample size substantially. Even so, the study supports the idea that preoperative NHT may offer functional benefits in addition to cancer control, especially by improving early urinary continence recovery after RARP.

This systematic review and meta-analysis examined whether leptin, a hormone made mainly by fat tissue, contributes to fertility problems in men with varicocele. Two reviewers searched five databases through July 2025 following PRISMA guidelines, ultimately pooling five case-control studies (205 patients, 119 fertile controls).

Main findings:

The authors suggest leptin in seminal plasma, rather than blood, may drive sperm dysfunction, possibly through ROS-mediated apoptosis, hypoxia (HIF-1α) signaling, and reduced testosterone. They caution that few studies, small samples, and an inability to assess publication bias limit the conclusions. Overall, seminal leptin appears to be a promising biomarker and therapeutic target for varicocele-related infertility, pending further study.

This real-world, retrospective single-center study examined the safety and effectiveness of an initial 0.1 mg desmopressin tablet in 234 Taiwanese men aged 60–95 with nocturia (≥2 voids/night) and nocturnal polyuria. A key aim was comparing outcomes between men younger than 80 and those 80 or older. Follow-up data were available for 208 patients (88.9%), and 70.1% completed the full 3-month course.

Effectiveness: After one month, all nocturia-related measures improved significantly in both age groups, reduced nocturnal urine volume (by more than 50%), fewer nighttime voids (about 2–3 fewer per night), and over an hour more undisturbed sleep. Men 80 and older showed comparable benefit despite more severe baseline symptoms. About a third of patients in each group rated themselves "much" or "very much" better.

Safety: Hyponatremia led to discontinuation in 39 of 234 patients (16.7%), with a higher rate in those 80 and older (26.8% vs 15.8%). However, 28 patients whose sodium dropped were able to continue the full three months after dose adjustments, and all hyponatremia events were mild and reversed once treatment stopped. Multivariate analysis identified older age and lower baseline sodium as the only significant independent predictors of hyponatremia.

Limitations: The study was retrospective, single-center, and lacked a comparator arm. All patients were Taiwanese (limiting generalizability), concomitant medications were continued (possible confounding), no correction for multiple testing was applied, and several patients dropped out without follow-up data.

Conclusion: A starting dose of 0.1 mg desmopressin is effective and well tolerated in older men with nocturnal polyuria. Regular serum sodium monitoring, particularly at months 1, 2, and 3 and especially in men 80 or older or with other risk factors plus individualized dose adjustment can help balance benefit against hyponatremia risk.

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