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Melanoma of unknown primary with solitary lesions to the prostate and lung uncovered after simple prostatectomy.

This case report details two clinical rarities of malignant melanoma isolated to the prostate and lung. Prostate melanoma is scarce in literature and predominantly a metastatic finding. However, rare cases of primary prostatic melanoma are reported. Primary lung melanoma is also rare. This case began after surgical correction of an inguinal bladder hernia complicated by postoperative, refractory clot urinary retention; ultimately requiring simple prostatectomy with pathology revealing malignant melanoma. Coinciding biopsy of a solitary pulmonary nodule revealed melanoma. This case details melanoma of the prostate or lung with unknown primary and solitary metastasis incidentally uncovered during simple prostatectomy.

Genomic testing

The impact of prehabilitation on postoperative outcomes in patients undergoing radical prostatectomy for prostate cancer: a systematic review and meta-analysis.

PURPOSE: Preoperative rehabilitation training can optimize functional reserve before radical prostatectomy (RP), thereby improving postoperative outcomes. However, its effects on urinary incontinence, erectile function, and quality of life (QoL) remain controversial. This study systematically evaluated these outcome measures. METHODS: Data from randomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, Embase, and CINAHL databases. The risk of bias was assessed using the RoB-2 tool, and meta-analysis was performed using Stata 18.0 software. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Meta-analyses were conducted using fixed- or random-effects models according to heterogeneity. Outcomes included urinary incontinence incidence, urinary incontinence severity, erectile function, and QoL at different postoperative follow-up time points. RESULTS: 16 randomized controlled trials involving 1,542 participants were included. Prehabilitation significantly reduced the incidence of urinary incontinence at 1 month (OR = 0.58, 95% CI 0.39-0.84) and 6 months (OR = 0.52, 95% CI 0.28-0.96) after RP, with a non-significant borderline reduction at 3 months, and no significant benefit at 12 months. No significant improvement was observed in urinary incontinence severity or erectile function at any follow-up time point. Prehabilitation significantly improved QoL within 3 months (SMD = -0.70, 95% CI -1.08 to -0.32) and 6 months (SMD = -0.45, 95% CI -0.74 to -0.16) postoperatively. However, within 12 months, the effect size attenuated, showing only a marginal trend that did not reach statistical significance (SMD = -0.33, 95% CI -0.66 to 0.00). Risk of bias was generally moderate. CONCLUSION: Prehabilitation reduces early incontinence and improves QoL post-RP, but its effects on severity and erectile function remain unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO [CRD420251183407].

Humans

Could the preoperative urethral curve be used to predict immediate urinary continence following Retzius-sparing robot-assisted radical prostatectomy? A retrospective multi-center study.

PURPOSE: Immediate urinary continence (UC) recovery following Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) remains highly variable, highlighting the need for reliable preoperative prediction. We aimed to develop and validate models to identify patients likely to achieve immediate UC recovery following RS-RARP. MATERIALS AND METHODS: A total of 580 prostate cancer patients who underwent RS-RARP from four medical centers were assigned to a training set (n=348), an internal validation set (n=103) and an external validation set (n=129). Independent predictors were identified through univariate analysis and LASSO regression. A nomogram was constructed using multivariate logistic regression. Its performance was evaluated with receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis. RESULTS: Immediate UC recovery was observed in 84.5% (294/348) of patients in the training cohort, 80.6% (83/103) in the internal validation cohort, and 81.4% (105/129) in the external validation cohort, respectively. Multivariate analysis identified membranous urethral length (MUL) (OR=1.23, P=0.029) and urethral curvature (OR=2.84, P<0.001) as independent predictors, while prostate volume (PV) (OR=0.84, P <0.001) as a protective factor. The nomogram integrating MUL, PV, and urethral curvature demonstrated superior predictive accuracy, with an AUC of 0.87 (95% CI, 0.83-0.91) in the training cohort. The bootstrap-corrected calibration slope was 0.96, and the Brier score was 0.08.&#xa0;Calibration curves and decision curve analysis confirmed the predictive accuracy and clinical utility of the nomogram. CONCLUSIONS: Our study introduces a novel quantitative method for assessing urethral curvature. The mpMRI-based model, integrating urethral curvature and prostate spatial configuration, offers enhanced predictive accuracy for postoperative immediate UC recovery.

Humans

Understanding randomized controlled trial generalizability through an embedded molecular diagnostics trial.

BACKGROUND: Issues with randomized controlled trial generalizability are well described, but whether these issues result from differences in patient treatment across contexts remains unknown. We studied treatment of patients with high-risk prostate cancer after radical prostatectomy inside and outside a randomized controlled trial evaluating the impact of a genomic classifier on post-radical prostatectomy treatment decision making (Genomics in Michigan Impacting Observation of Radiation [G-MINOR]; ClinicalTrials.gov identifier NCT02783950). METHODS: G-MINOR enrolled 338 patients; propensity score-matched eligible but unenrolled patient cohorts (pretrial and trial contemporary) from the Michigan Urological Surgery Improvement Collaborative (MUSIC), in which the trial was embedded, were compared for rates and time to secondary treatment (adjuvant or salvage therapy) after prostatectomy. RESULTS: Among 338 patients in the G-MINOR cohort, 69 (31 adjuvant, 38 salvage) received secondary treatment compared with 266 (183 adjuvant, 83 salvage) and 104 (60 adjuvant, 44 salvage) in the 1014 contemporary and 338 pretrial-matched MUSIC cohorts. Time to secondary treatment was much shorter in the MUSIC cohort across all comparisons. For example, matching G-MINOR to synchronous MUSIC patients demonstrated 84% vs 74% estimated 2-year treatment-free survival for trial and real-world patients, respectively (P&#x2009;<&#x2009;.001). CONCLUSIONS: Controlling for key clinicopathologic factors, patients in the G-MINOR randomized controlled trial and MUSIC cohorts were treated differently, even after stratifying by genomic risk. These findings suggest that challenges in randomized controlled trial generalizability extend beyond the representativeness of trial participants. Differences in management may also explain why divergent patient outcomes are observed in randomized controlled trials vs real-world settings.

Aged

Large Language Model and Knowledge Graph-Driven AJCC Staging of Prostate Cancer Using Pathology Reports.

Background/Objectives: To develop an automated American Joint Committee on Cancer (AJCC) staging system for radical prostatectomy pathology reports using large language model-based information extraction and knowledge graph validation. Methods: Pathology reports from 152 radical prostatectomy patients were used. Five additional parameters (Prostate-specific antigen (PSA) level, metastasis stage (M-stage), extraprostatic extension, seminal vesicle invasion, and perineural invasion) were extracted using GPT-4.1 with zero-shot prompting. A knowledge graph was constructed to model pathological relationships and implement rule-based AJCC staging with consistency validation. Information extraction performance was evaluated using a local open-source large language model (LLM) (Mistral-Small-3.2-24B-Instruct) across 16 parameters. The LLM-extracted information was integrated into the knowledge graph for automated AJCC staging classification and data consistency validation. The developed system was further validated using pathology reports from 88 radical prostatectomy patients in The Cancer Genome Atlas (TCGA) dataset. Results: Information extraction achieved an accuracy of 0.973 and an F1-score of 0.986 on the internal dataset, and 0.938 and 0.968, respectively, on external validation. AJCC staging classification showed macro-averaged F1-scores of 0.930 and 0.833 for the internal and external datasets, respectively. Knowledge graph-based validation detected data inconsistencies in 5 of 150 cases (3.3%). Conclusions: This study demonstrates the feasibility of automated AJCC staging through the integration of large language model information extraction and knowledge graph-based validation. The resulting system enables privacy-protected clinical decision support for cancer staging applications with extensibility to broader oncologic domains.

artificial intelligence

Sociodemographic trends in prostate cancer: insights from the All of Us Research Program.

BACKGROUND: Prostate cancer disproportionately affects vulnerable populations. The All of Us Research Program (AoURP) is a database that aims to encapsulate the diversity of the United States. To explore the utility of this dataset in assessing prostate cancer disparities, we investigated whether treatment usage, disease progression, and genomic research participation vary across sociodemographic factors among AoURP participants with prostate cancer. METHODS: We identified AoURP participants with prostate cancer. Genomic research participation in AoURP, treatment usage, time-to-treatment, and time-to-metastasis were assessed by demographics and distance from a National Cancer Institute-designated comprehensive cancer center. Multivariable logistic regression and Cox proportional hazards regression were performed to evaluate treatment usage and time-to-treatment and time-to-metastasis, respectively. RESULTS: We observed lower genomic data availability in Black vs White patients (P&#x2009;<&#x2009;.001). In multivariable analyses, patients residing more than 80 miles from an NCI-designated comprehensive cancer center were less likely to receive androgen receptor pathway inhibitors (odds ratio [OR]&#x2009;=&#x2009;0.30, 95% CI = 0.14 to 0.66; P&#x2009;=&#x2009;.002) and bone targeting agents (OR&#x2009;=&#x2009;0.46, 95% CI = 0.30 to 0.70; P&#x2009;<&#x2009;.001) but more likely to undergo prostatectomy (OR&#x2009;=&#x2009;1.97, 95% CI = 1.43 to 2.71; P&#x2009;<&#x2009;.001) than those&#x2009;residing less than&#x2009;40 miles away. These patients also initiated treatment faster (hazard ratio [HR]&#x2009;=&#x2009;1.54, 95% CI = 1.27 to 1.87; P&#x2009;<&#x2009;.001) and developed metastasis slower (HR&#x2009;=&#x2009;0.58, 95% CI = 0.40 to 0.86; P&#x2009;=&#x2009;.006). Black patients were less likely to receive radiation (OR&#x2009;=&#x2009;0.45, 95% CI = 0.23 to 0.88; P&#x2009;=&#x2009;.020), prostatectomy (OR&#x2009;=&#x2009;0.65, 95% CI = 0.44 to 0.96; P&#x2009;=&#x2009;.028), and bone targeting agents (OR&#x2009;=&#x2009;0.65, 95% CI = 0.45 to 0.93; P&#x2009;=&#x2009;.018) than White patients. CONCLUSIONS: Prostate cancer treatment usage, disease progression, and genomic research participation varied between demographic populations. As AoURP matures, additional studies may leverage future data releases to confirm these findings.

Aged

Subclonal Complete Loss of CDKN1B as a Common Genomic Alteration in Prostate Cancer: Associations with Race and Prostate Cancer Outcomes.

BACKGROUND: Homozygous biallelic inactivation of CDKN1B is thought to be rare in cancer. Herein we evaluate the prevalence of intratumoral (subclonal) complete p27 protein loss (IPPL) in primary prostate cancer. EXPERIMENTAL DESIGN: We used immunohistochemistry (IHC) for p27 in a large cohort of whole tissue sections from radical prostatectomy (n=412) and metastases from self-identified African American (AA) and European American (EA) individuals. IPPL was evaluated alongside CDKN1B mRNA in-situ hybridization and next generation sequencing of laser captured cancer regions. Cox proportional hazards analyses assessed the association of IPPL with biochemical recurrence and development of metastases after radical prostatectomy. RESULTS: IPPL was detected in 18.1% of AA versus 12.2% of EA cases and was tightly correlated with CDKN1B mRNA loss and biallelic genomic loss. IPPL was associated with &#x2265;pT3 pathologic stage and pN1 disease, however these associations were only significant among AA participants. IPPL was further associated in both univariate and multivariate analyses with the development of biochemical recurrence and metastasis after primary treatment, specifically in AA individuals. The prevalence of p27 genomic alterations in metastatic disease is higher than that of primary prostate cancer in publicly available datasets as well as our analysis of autopsy cases via IHC, indicating that complete p27 loss may be selected for in metastatic disease. CONCLUSIONS: Subclonal biallelic loss of CDKN1B resulting in complete p27 protein loss is one of the most commonly occurring biallelic tumor suppressor genomic alterations in primary prostate cancer, and could contribute to worse prostate cancer outcomes, specifically in AA males.

Journal Article

Effect of demographic characteristics on the outcome of prostate cancer salvage radiotherapy: Analysis from a randomized controlled trial.

BACKGROUND: This study investigated the impact of advanced molecular imaging, race, socioeconomic status, and metabolic dysregulation on the outcome of salvage radiotherapy (sRT) for prostate cancer recurrence in a clinical trial setting. METHODS: The authors randomized post-prostatectomy men with detectable prostate-specific antigen to sRT guided by conventional imaging (arm A) or 18F-fluciclovine-positron emission tomography/computed tomography (arm B) and followed them up for up to 48 months to determine failure-free survival (FFS). The authors computed socioeconomic status (SES) and allostatic load (AL) scores to quantify socioeconomic status and level of metabolic dysregulation. They stratified patients by race as African American men (AAM) versus men of other races (MOR) and compared FFS between them using the z-test. RESULTS: Eighty-one (AAM&#xa0;=&#xa0;29, MOR&#xa0;=&#xa0;52) and 76 (AAM&#xa0;=&#xa0;26, MOR&#xa0;=&#xa0;50) men completed per-protocol sRT in arms A and B, respectively. Across study arms, AAM showed a higher FFS rate than MOR (72.8% [95% CI, 53.8%-85.0%] vs. 58.7% [95% CI, 46.6%-68.9%]; p&#xa0;=&#xa0;.002). In arm A, FFS rate was better for AAM than MOR, (64.0% [95% CI, 34.4%-82.9%] vs. 45.3% [95% CI, 28.8%-60.4%]; p&#xa0;=&#xa0;.008). In arm B, FFS improved for both groups but less so for AAM, (81.5% [95% CI, 57.2%-92.7%] vs. 73.0% [95% CI, 56.3%-84.1%]; p&#xa0;=&#xa0;.131). The authors found lower SES scores and higher AL scores for AAM in both study arms than MOR. CONCLUSION: Despite lower socioeconomic status and higher burden of metabolic dysregulation, in a clinical trial setting that controls for disparities in health care access, AAM have a more favorable sRT outcome than MOR.

Humans

Histopathologic Features and Transcriptomic Signatures Do Not Solve the Issue of Magnetic Resonance Imaging-Invisible Prostate Cancers: A Matched-Pair Analysis.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) is pivotal in prostate cancer (PCa) diagnosis, but some clinically significant (cs) PCa remain undetected. This study aims to understand the pathological and molecular basis for csPCa visibility at mpMRI. METHODS: We performed a retrospective matched-pair cohort study, including patients undergoing radical prostatectomy (RP) for csPCa (i.e., ISUP grade group &#x2265;&#x2009;2) from 2015 to 2020, in our tertiary-referral center. We screened for inclusion in the "mpMRI-invisible" cohort all consecutive men (N&#x2009;=&#x2009;45) having a negative preoperative mpMRI. The "mpMRI-visible" cohort was matched based on age, PSA, prostate volume, ISUP grade group. Included patients underwent radiological and pathological open-label revisions and characterization of the tumor mRNA expression profile (analyzing 780 gene transcripts, signaling pathways, and cell-type profiling). We compared the clinical-pathological variables and the gene expression profile between matched pairs. The analysis was stratified according to histological characteristics and lesion diameter. RESULTS: We included 34 patients (17 per cohort); mean age at RP and PSA were 70.5 years (standard deviation [SD]&#x2009;=&#x2009;7.7), 7.1&#x2009;ng/mL (SD&#x2009;=&#x2009;3.3), respectively; 65% of men were ISUP 2. Overall, no significant differences in histopathological features, tumor diameter and location, mRNA profile, pathways, and cell-type scores emerged between cohorts. In the stratified analysis, an upregulation of cell adhesion and motility, of extracellular matrix remodeling and of metastatic process pathways was present in specific subgroups of mpMRI-invisible cancers. CONCLUSIONS: No PCa pathological or gene-expression hallmarks explaining mp-MRI invisibility were identified. Aggressive features can be present both in mpMRI-invisible and -visible tumors.

Humans

Characterizing the Activity of Inflammasome-Related Genes and Their Association With Oncological Outcomes in Prostate Cancer.

BACKGROUND: Inflammation plays a critical role in cancer cell proliferation; however, the specific role of inflammasomes, multiprotein complexes that regulate inflammation-associated signaling pathways, in prostate cancer (PCa) remains insufficiently explored. This study aims to characterize the expression of inflammasome-related genes in PCa and evaluate their association with clinical outcomes. METHODS: De-identified transcriptome data from the Decipher GRID RP, a cohort of 52,266 radical prostatectomy (RP) samples tested (2016-2024) with the Decipher prostate genomic classifier (Veracyte, San Diego, CA), were retrieved from the GRID registry (NCT02609269). Expression analysis of 34 genes involved in inflammatory pathways was conducted to associate their expression with clinical and genomic variables. Outcomes analyses were conducted on a retrospective cohort of 855 patients treated with RP (META855). RESULTS: Analysis of inflammasome gene expression in the GRID RP cohort revealed that most genes exhibit low baseline expression, whereas HSP90AB1, APP, TXN, and TXNIP demonstrate strong expression signals. Additionally, higher expression of most genes was associated with Gleason Grade Group 4-5 and very high Decipher scores. On survival analysis of the META855 cohort, higher expressions of AIM2 and HSP90AB1 were significantly associated with worse metastasis-free survival. Conversely, both high and low expression levels of NLRP3 were associated with better metastasis-free survival outcomes following RP compared to average expression. On multivariable Cox regression analysis, higher expressions of AIM2 (HR 1.75) and HSP90AB1 (HR 1.60) were significantly associated with shorter time to metastasis following RP. CONCLUSIONS: There is molecular heterogeneity within pro-inflammatory genes among patients with PCa. Our findings showed there is a potential association between the expression levels of certain inflammasomes, such as AIM2, HSP90AB1, and NLRP3, and oncological outcomes following RP.

Aged

RADA16 as a novel hemostatic and regenerative agent in urology: European Association of Urology endourology up-to-date overview.

PURPOSE OF REVIEW: Self-assembling peptide (SAP) hydrogels represent a novel class of synthetic biomaterials with growing relevance in surgery. Among them, the ion-complementary peptide RADA16 has gained attention as an athermal, transparent, and biocompatible hemostatic agent. While its use is increasingly reported in multiple surgical specialties, evidence specific to urology remains fragmented. This review aims to summarize the physicochemical properties, mechanisms of action, and current clinical evidence for RADA16-based hydrogels, with a particular focus on urological applications. RECENT FINDINGS: RADA16 rapidly self-assembles into a transparent, extracellular-matrix-like nanofibrillar hydrogel upon exposure to physiological fluids, providing effective local hemostasis without reliance on the coagulation cascade. Preclinical and clinical data from other surgical fields demonstrate rapid bleeding control, favorable safety, and potential regenerative effects. Emerging urological evidence suggests that RADA16 is effective in managing hemorrhagic cystitis, radiation-induced hematuria, and bleeding during prostate surgery, including robot-assisted radical prostatectomy and benign prostate surgery. Beyond hemostasis, RADA16 may support wound healing and promotion of re-epithelialization. However, the current evidence base is limited by small sample sizes, lack of comparative studies, heterogeneous methodologies, and short follow-up. SUMMARY: RADA16-based hydrogels represent a promising adjunctive hemostatic option in urology, offering technical advantages such as transparency, absence of thermal injury, minimal swelling, and applicability in confined or high-risk settings. Robust prospective, comparative, and cost-effectiveness studies are required to define its definitive role in routine urological practice.

Humans

A Prospective Validation of the Decipher Genomic Classifier in Men With Early Localized Prostate Cancer: The VANDAAM Study.

BACKGROUND: The emergence of genomic precision oncology has advanced personalized care for some patients with prostate cancer (PCa), while threatening to widen existing disparities due to the historically low recruitment of African American men (AAM), who have the highest disease burden. Here, we report the first prospective validation of a genomic classifier (GC) to predict rapid-onset biochemical recurrence (BCR) in AAM. METHODS: Between 2016 and 2021, this multicenter prospective validation study recruited 243 patients with low- or intermediate-risk PCa who received treatment for their disease. Patients were recruited on a 1:1 basis (AAM:White) and matched by CAPRA score. Patients who elected active surveillance were ineligible for participation. Decipher GC testing was ordered for all patients using their biopsy and/or radical prostatectomy (RP) tumor tissue. The primary outcome was to determine whether the GC could predict 2-year BCR rates-used as a surrogate for disease aggressiveness-following standard treatment. The secondary outcome evaluated the concordance between biopsy- and RP-derived GC risk scores for treatment recommendations. RESULTS: The final analytical cohort included 226 matched patients with genomic information, and 207 evaluable cases (104 AAM, 103 White) with both genomic and complete clinical outcome data. Overall, a high genomic-risk GC score was associated with a 5.25-fold increase in the odds of rapid-onset 2-year BCR compared with the low-risk group (odds ratio, 5.25 [95% CI, 1.27-21.66]; P=.021). In a subset of the surgical cohort (n=74), biopsy- and RP-derived GC scores exhibited a 77% concordance rate, defined as no reclassification in GC risk-based categories. CONCLUSIONS: This study represents the first prospective validation of GC performance in predicting early 2-year BCR in both AAM and White men. The findings provide strong evidence supporting the integration of the GC into clinical practice guidelines to improve risk stratification and management of AAM with early-stage PCa. CLINICALTRIALS: gov identifier: NCT02723734.

Aged

Holmium laser enucleation of the prostate for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.

RATIONALE: A range of surgical options is available for the treatment of benign prostatic hyperplasia (BPH), including holmium laser enucleation of the prostate (HoLEP). The evidence is unclear regarding differences in functional, perioperative, and morbidity outcomes between these modalities. OBJECTIVES: To assess the effects of holmium laser enucleation of the prostate compared with other surgical treatments for lower urinary tract symptoms in men with benign prostatic hyperplasia. SEARCH METHODS: We searched multiple databases (including MEDLINE, Embase, CENTRAL, Web of Science, LILACS, and the International HTA database), trial registries, and conference abstracts through April 08, 2026. ELIGIBILITY CRITERIA: We only included randomized trials of men over 40 years of age with a prostate volume of at least 20 mL (assessed by digital rectal examination, ultrasound, or conventional imaging) who exhibited lower urinary tract symptoms (LUTS) defined by an International Prostate Symptom Score (IPSS) of eight or greater undergoing surgical interventions for BPH. OUTCOMES: The critical outcomes measured were the urologic symptoms score, the quality-of-life score, and major adverse events. The important outcomes measured were: re-treatment, erectile function, ejaculatory function, transfusions, acute urinary retention, indwelling urinary catheter duration, and hospital stay duration. RISK OF BIAS: We used the Cochrane risk of bias tool (RoB 1) to assess for potential sources of bias on a study and outcome level basis. SYNTHESIS METHODS: We pooled outcome data using the random-effects model and performed meta-analyses using the Mantel-Haenszel method. We assessed statistical heterogeneity in the pooled data by visually inspecting forest plots and using the I2 statistic to quantify it. We used the GRADE framework to assess the certainty of evidence. INCLUDED STUDIES: We included 52 trials that included 6242 participants that compared HoLEP to other surgical interventions for benign prostatic hyperplasia. The median age of participants across the studies ranged from 65 to 74 years. The baseline prostate volume ranged from 30 cc to 142 cc. Baseline IPSS scores ranged from 19.6 to 28.6 (range 0-35). SYNTHESIS OF RESULTS: We prioritized comparing HoLEP with transurethral resection of the prostate (TURP) at short-term follow-up (up to 12 months), because TURP is the long-standing reference standard and the predominant comparator in randomized surgical trials. Findings for the four remaining comparisons (laser ablation, alternative energy source enucleation, other minimally invasive therapies, and simple prostatectomy), for long-term follow-up, and for all remaining outcomes are reported in full in the review. Compared to TURP, at short-term follow-up: Critical outcomes - HoLEP may result in little to no difference in short-term urologic symptom scores measured using the IPSS (range 0 to 35; lower values reflect fewer symptoms) (MD -0.67, 95% CI -1.20 to -0.14; I&#xb2; = 93%; 14 studies, 1666 participants, low-certainty evidence). - HoLEP may result in little to no difference in short-term quality of life (range 0 to 6; lower values reflect better quality of life) (MD -0.04, 95% CI -0.23 to 0.15; I&#xb2; = 73%; 6 studies, 876 participants, low-certainty evidence). - HoLEP may result in little to no difference in short-term major adverse events (RR 0.75, 95% CI 0.35 to 1.58; I&#xb2; = 0%; 10 studies, 1147 participants, low-certainty evidence). Important outcomes - HoLEP likely results in little to no difference in re-treatment (RR 0.45, 95% CI 0.14 to 1.50; I&#xb2; = 0%; 8 studies, 813 participants, moderate-certainty evidence). - HoLEP likely results in little to no difference in erectile function (MD -0.03, 95% CI -0.47 to 0.42; I&#xb2; = 0%; 3 studies, 518 participants, moderate-certainty evidence). - Ejaculatory function: we did not find any data for this outcome. - HoLEP likely reduces the need for blood transfusion (RR 0.19, 95% CI 0.09 to 0.42; I&#xb2; = 0%; 15 studies, 1755 participants, moderate-certainty evidence). AUTHORS' CONCLUSIONS: Compared with TURP, HoLEP may achieve similar relief of urologic symptoms, similar quality of life, and similar rates of major adverse events in the first 12 months after surgery, and probably similar re-treatment rates and erectile function. HoLEP likely reduces the need for blood transfusion; this is the only advantage of HoLEP that the randomized evidence, as summarized here, supports as clinically important. There was insufficient evidence to assess outcomes in the subset of individuals with larger prostates or on anticoagulation. Future research should prioritize long-term trials reporting sexual function and urinary incontinence outcomes, recruit men with very large prostates (&#x2265; 150 cc) or on anticoagulation therapy, and evaluate cost-effectiveness and training requirements. FUNDING: No external funding was received for this review. REGISTRATION: The protocol for this review was published in the Cochrane Database 2019 (https://doi.org/10.1002/14651858.CD013291).

Humans

A transition zone enriched WIF1+ basal cell subtype is associated with benign prostatic hyperplasia.

The cellular composition and disease susceptibilities of the distinct zones of the human prostate remain incompletely understood. Benign prostatic hyperplasia (BPH) is a common condition that causes widespread morbidity and is nearly exclusively localized to the transition zone (TZ). Through extensive single-cell RNA sequencing (scRNA-seq) of benign regions from prostatectomy specimens, we identified a basal cell population expressing WIF1, VCAN, and NRG1, among other genes, that was significantly enriched in the TZ. Analysis of previously published scRNA-seq datasets further confirmed that WIF1+ basal cells were significantly enriched in BPH compared with normal prostate. Pathway and cell-cell communication analyses revealed that this basal subtype is associated with programs related to cell proliferation, epithelial-mesenchymal transition, immune regulation, angiogenesis, and hormone response. Together, the molecular signature, zonal distribution, and pathway enrichment suggest that TZ-enriched WIF1+ basal cells may contribute to BPH pathogenesis by promoting epithelial and stromal remodeling. &#xa9; 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

NRG1

Subclonal Complete Loss of CDKN1B as a Common Genomic Alteration in Prostate Cancer: Associations With Race and Prostate Cancer Outcomes.

Homozygous biallelic inactivation of CDKN1B is thought to be rare in cancer, including prostate cancer. In the present study, we report that the prevalence of subclonal genomic loss of CDKN1B, especially among self-reported African-American or Black (AA) individuals, has likely been underestimated in primary prostate cancer. Using immunohistochemistry (IHC) for p27 protein and a large cohort of whole tissue sections from radical prostatectomy (N = 412) from AA and European American (EA) individuals, we discovered an unexpectedly high frequency of regions of intratumoral complete p27 protein loss (IPPL) within larger tumor nodules that otherwise showed intact p27 staining that was more prevalent among prostate cancer in AA individuals (18.1%) than EA individuals (12.2%). Regions of IPPL were tightly associated with loss of CDKN1B messenger RNA by in situ hybridization. Furthermore, these focal regions of IPPL were closely linked to CDKN1B genomic loss as detected by next-generation sequencing panel sequencing of laser-captured regions. The detection of IPPL by IHC was associated with &#x2265;pT3 pathologic stage (extraprostatic extension and seminal vesicle involvement) and pN1 (local lymph node involvement) disease; however, when stratified by race, these associations were only significant among AA participants. IPPL was further associated in both univariate and multivariate analyses with the development of biochemical recurrence and metastasis after primary treatment, specifically in AA individuals. The prevalence of p27 genomic alterations in metastatic disease is higher than that of primary prostate cancer in publicly available data sets as well as in our analysis of autopsy specimens via IHC. Overall, subclonal biallelic loss of CDKN1B resulting in complete p27 protein loss is one of the most commonly occurring biallelic tumor suppressor genomic alterations in primary prostate cancer and could contribute to worse prostate cancer outcomes, specifically in AA individuals. Our findings warrant further exploration into the clinical utility of using IHC for p27 loss as a prognostic biomarker.

CDKN1B cancer disparities

Salvage therapy for radiorecurrent prostate cancer: beyond equipoise - a call for biomarker-driven stratification.

The increasing incidence of localized radiorecurrent prostate cancer demands a shift from modality-centric comparisons toward biomarker-driven patient selection. Light et al. provide a matched comparison of salvage focal therapy (sFT) versus salvage radical prostatectomy (sRP), reporting comparable 10-year cancer-specific survival but fewer complications with sFT. However, the study lacks integration of modern PSMA PET/CT restaging and genomic risk stratification (e.g., Decipher classifier), both of which could profoundly influence therapeutic outcomes. Moreover, salvage reirradiation-a promising third option-is omitted. We argue that equipoise is no longer sufficient; the field needs prospective registries or trials that stratify by imaging and genomic biomarkers, with coprimary endpoints of metastasis-free survival and patient-reported functional outcomes. We also discuss the limitations of PSMA PET/CT for small-volume lesions and the importance of validating genomic thresholds specifically in the salvage setting. Only such an approach will enable truly personalized salvage therapy.

Biomarker stratification

Spatially organized lymphocytic microenvironments in high grade primary prostate tumors.

The spatial organization and composition of the tumor-immune microenvironment (TME) play a critical role in shaping the progression of many solid cancers, but the organization of the TME in primary prostate cancer (PCa) remains poorly characterized. We therefore profiled the abundance and spatial distributions of major cell types involved in adaptive immunity in 29 radical prostatectomy specimens stratified into high (HGG; n=14) and low Gleason-grade (LGG; n=15). Compared to LGG, HGG PCa exhibited significantly greater B and T cell infiltration with many immune cells organized into clusters, some of which resembled tertiary lymphoid structures (TLSs). In HGG tumors, these clusters were dense, symmetric, rich in PD-1+ T cells, and frequently proximate to the tumor compartment. LGG clusters were less well organized, and T cell depleted. Thus, a subset of high-grade PCa harbor organized immune clusters that may play a role in tumor control and contain therapeutically targetable T and B cells.

Prostate cancer

Post-operative pain, nausea, vomiting and optic nerve sheath diameter following total intravenous versus inhalational anesthesia for adults undergoing robotic transabdominal surgery - a systematic review and meta- analysis.

BACKGROUND: The introduction of robotic-assisted abdominal surgery is aimed at reducing the primary and secondary adverse outcomes. Anesthesia in robotic surgery varies from anesthesia for open or laparoscopic surgical procedures. The choice of anesthesia influences the perioperative control of pain, nausea, vomiting, and Optic nerve sheath diameter (ONSD). The purpose of this systematic review was to assess outcome variation in patients undergoing transabdominal robot-assisted surgery done under total intravenous anesthesia or inhalational anesthesia. METHODOLOGY: We searched the Cochrane Central Register of Controlled Trials, PubMed, and Google Scholar (January, 2017 to June, 2024). Search terms included "Anesthesia", "Robotics", "prostatectomy", hysterectomy", "nephrectomy", "cholecystectomy" and "cystectomy" with the Boolean operators "AND" and "OR". We searched for randomized controlled trials (RCTs) including adults of both genders aged 18 years and above, who underwent transabdominal robotic-assisted laparoscopic surgery and targeting the consequences related to TIVA or inhalational anesthesia. We reviewed titles and abstracts and proceeded to full-text articles of the eligible studies relevant to inclusion criteria. Mean and standard deviations with 95% CI were calculated. Forest plots were used to present data visually. RESULTS: Six studies (340 patients) were included. We found only one study in which post-operative pain was assessed and results favored intravenous anesthesia in robotic transabdominal surgery. Only two studies reported post-operative nausea and vomiting (PONV). Both studies stated that PONV is reported in few patients in the inhalation anesthesia group. We found evidence suggesting that change in ONSD measurements at 10&#xa0;min after induction (MD 0.04,95% CI -0.02 to 0.11 p&#x2009;=&#x2009;0.19) and 40-60&#xa0;min after Trendelenburg position (MD -0.26, 95% CI -0.34 to 0.17, p&#x2009;=&#x2009;0.16) are much less in intravenous anesthesia group than in inhalation anesthesia group. Total intravenous anesthesia maintains the ONSD and hence the ICP better than inhalational anesthesia in robotic transabdominal surgery with CO2 pneumoperitoneum in Trendelenburg positioning requirements. It would be a safer choice than inhalational anesthesia due to fewer adverse events. CONCLUSION: This review concludes that TIVA is a better choice than inhalational anesthesia for transabdominal robotic-assisted surgery in urology, gynecology, and gastroenterology in both male and female patients.

Humans