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Purpose: Serial biopsy is a mainstay for patients on active surveillance (AS) for prostate cancer. mpMRI targeting has become a standard. It is unclear whether targeted biopsy alone reliably identifies the dominant lesion, thereby obviating the need for systematic sampling., Materials and Methods: Participants enrolled in AS with early-stage prostate cancer (PSA < 20, cT1-2, GG1-2) and underwent 2+ systematic biopsy sessions with or without MR-targeted sampling. The findings for dominant Gleason Grade (GG) and tumor localization were assessed., Results: Among 821 men who underwent MR fusion biopsies, 82% were diagnosed with GG1 and 18% with GG2. Sixty-two percent had their first MR fusion biopsy as diagnostic or confirmatory. Across all fusion biopsies, MRI-targeted detection of GG and/or tumor location overlapped with systematic sampling for 95% of cases. For 5% of cases, systematic biopsy was unique in detecting GG and location outside the target. Most unique lesions detected outside the target had marginally aggressive features: 73% GG2 of low-volume and favorable histologic subtypes., Conclusions: In men with MR fusion biopsies, targeting alone identified the dominant GG and location most of the time (95%); 25% of dominant lesions were contiguous to the target, suggesting that better sampling of the target improves detection. The remaining 5% of men had higher-grade, low-volume disease outside the targeted lesion of which only 2% had aggressive risk features. MR fusion targeting, without systematic sampling, may be sufficient to monitor men on AS. Few high-risk cancers are missed, all of limited volume and favorable histology.

Importance: The association between radiotherapy (RT) timing after radical prostatectomy and long-term patient-reported health-related quality of life (HRQOL) in men with prostate cancer is unknown., Objective: To measure long-term HRQOL in men with prostate cancer up to 15 years after prostatectomy with or without RT and examine whether early vs late postprostatectomy RT is associated with differences in sexual, urinary, and bowel HRQOL., Design, Setting, and Participants: A prospective, multicenter, longitudinal cohort analysis using HRQOL data from the PROST-QA (2003-2006) and RP2 consortium (2010-2013) studies was conducted. Men with localized prostate cancer undergoing radical prostatectomy were included. Data were analyzed between May 8, 2023, and March 1, 2024. The study was conducted in 12 high-volume academic medical centers in the US., Exposures: Men were stratified based on receipt and timing of postprostatectomy RT: prostatectomy only, early RT (<12 months), and late RT (≥12 months)., Main Outcomes and Measures: Longitudinal sexual, incontinence, urinary irritation, bowel, and hormonal/vitality HRQOL were measured via the Expanded Prostate Cancer Index Composite at baseline; months 2, 6, and 12; and annually thereafter. Treatment groups were compared using multivariable linear mixed-effects models of change in longitudinal domain scores. Pad use for incontinence was measured longitudinally among men receiving postprostatectomy RT., Results: A total of 1203 men were included in the study: prostatectomy only (n = 1082), early RT (n = 57), and late RT (n = 64). Median age for the entire cohort was 60.5 (range, 38.8-79.7) years, and 1075 men (92.0%) were White. Median follow-up was 85.6 (IQR, 35.8-117.2) months. Compared with men receiving prostatectomy alone, those receiving postprostatectomy RT had significantly greater decreases in sexual, incontinence, and urinary irritation HRQOL. However, timing of postprostatectomy RT, specifically early vs late, was not associated with a long-term decrease in any HRQOL domain. There was evidence of improved recovery of sexual, continence, and urinary irritation scores among men receiving early RT compared with those receiving late RT after prostatectomy. Before the start of postprostatectomy RT, 39.3% of men in the early RT cohort and 73.4% of men in the late RT cohort were pad-free. By the sixth visit post-RT, 67.4% in the early RT cohort and 47.6% in the late RT cohort were pad-free., Conclusions and Relevance: In this multicenter, prospective analysis, postprostatectomy RT appeared to be negatively associated with long-term HRQOL across all domains. However, receipt of early vs late postprostatectomy RT may result in similar long-term HRQOL outcomes.

Aims: Histological grading of prostate cancer is a powerful prognostic tool, but current criteria for grade assignment are not fully optimised. Our goal was to develop and test a simplified histological grading model, based heavily on large cribriform/intraductal carcinoma, with optimised sensitivity for predicting metastatic potential., Methods and Results: Two separate non-overlapping cohorts were identified: a 419-patient post-radical prostatectomy cohort with long term clinical follow-up and a 209-patient post-radical prostatectomy cohort in which all patients had pathologically confirmed metastatic disease. All prostatectomies were re-reviewed for high-risk histological patterns of carcinoma termed 'unfavourable histology'. Unfavourable histology is defined by any classic Gleason pattern 5 component, any large cribriform morphology (> 0.25 mm) or intraductal carcinoma, complex intraluminal papillary architecture, grade 3 stromogenic carcinoma and complex anastomosing cord-like growth. For the outcome cohort, Kaplan-Meier analysis compared biochemical recurrence, metastasis and death between subjects with favourable and unfavourable histology, stratified by pathological stage and grade group. Multivariable Cox proportional hazards models evaluated adding unfavourable histology to the Memorial Sloan Kettering Cancer Center (MSKCC) post-prostatectomy nomogram and stratification by percentage of unfavourable histology. At 15 years unfavourable histology predicted biochemical recurrence, with sensitivity of 93% and specificity of 88%, metastatic disease at 100 and 48% and death at 100 and 46%. Grade group 2 prostate cancers with unfavourable histology were associated with metastasis independent of pathological stage, while those without had no risk. Histological models for prediction of metastasis based on only large cribriform/intraductal carcinoma or increasing diameter of cribriform size improved specificity, but with lower sensitivity. Multivariable Cox proportional hazards models demonstrated that unfavourable histology significantly improved discriminatory power of the MSKCC post-prostatectomy nomogram for biochemical failure (likelihood ratio test P < 0.001). In the retrospective review of a separate RP cohort in which all patients had confirmed metastatic disease, none had unequivocal favourable histology., Conclusions: Unfavourable histology at radical prostatectomy is associated with metastatic risk, predicted adverse outcomes better than current grading and staging systems and improved the MSKCC post-prostatectomy nomogram. Most importantly, unfavourable histology stratified grade group 2 prostate cancers into those with and without metastatic potential, independent of stage. While unfavourable histology is driven predominantly by large cribriform/intraductal carcinoma, the recognition and inclusion of other specific architectural patterns add to the sensitivity for predicting metastatic disease. Moreover, a simplified dichotomous model improves communication and could increase implementation., (© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.)

Background and Objective: Active surveillance (AS) of prostate cancer (PCa) is the standard of care for low-grade disease, but there is limited guidance on tailoring protocols for stable patients. We investigated long-term outcomes for patients without initial progression and risk factors for upgrade., Methods: Men on AS with Gleason grade group (GG) 1 PCa on three serial biopsies, ≥5 yr without progression, and ≥10 yr of follow-up were included. Outcomes were upgrade (GG ≥2), major upgrade (GG ≥3), progression to treatment, metastasis, PCa-specific survival, and overall survival. Cox proportional hazards regression models were used to estimate the associations between patient characteristics and risk of upgrade., Key Findings and Limitations: A total of 774 men met the inclusion criteria. At 10, 12, and 15 yr, upgrade-free survival rates were 56%, 45%, and 21%; major upgrade-free survival rates were 88%, 83%, and 61%; treatment-free survival rates were 86%, 83%, and 73%; metastasis-free survival rates were 99%, 99%, and 98%; and overall survival rates were 98%, 96%, and 95%, respectively. PCa-specific survival was 100% at 15 yr. On a multivariable analysis, year of diagnosis, age, body mass index (BMI), and biopsy core positivity were associated with upgrade (all p < 0.01), whereas age and prostate-specific antigen (PSA) density were associated with major upgrade., Conclusions and Clinical Implications: Patients without progression for 5 yr on AS had modest rates of upgrade and low rates of metastasis, and mortality at 15 yr of follow-up. Year of diagnosis, older age, increased BMI, and increased biopsy core positivity were associated with upgrade, whereas older age and greater PSA density were associated with an increased risk of major upgrade. A subset of these patients may benefit from deintensification of AS protocols., Patient Summary: There are little reported data or clinical guidelines for patients with PCa who are stable for many years on active surveillance (AS). We show, in a large cohort, that PCa patients without progression for 5 yr on AS have modest rates of upgrade and very low rates of metastasis, and mortality rates at 15 yr of follow-up, and that older age, increased body mass index, and increased PCa volume are associated with an increased likelihood of future upgrade. This study supports continued AS in this patient population and deintensification in select patients., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To establish the incidence, size, zonal location and Gleason Score(GS)/Gleason Grade Group(GG) of sparse versus dense prostate cancer (PCa) lesions and to identify the imaging characteristics of sparse versus dense cancers on multiparametric MRI (mpMRI)., Methods: Seventy-six men with untreated PCa were scanned prior to prostatectomy with endorectal-coil 3 T MRI including T2-weighted imaging, diffusion-weighted imaging and dynamic contrast-enhanced MRI. Cancerous regions were outlined and graded on the whole-mount, processed specimens, with tissue compositions estimated. Regions with cancer comprising <50 % and ≥ 50 % of the tissue were considered sparse and dense respectively. Regions of interest (ROI) were manually drawn on T2-weighted MRI. Within each patient, area-weighted ROI averages were calculated for each imaging measure for each tissue type, GS/GG, and sparse/dense composition., Results: A large number of cancer regions were identified on histopathology (n = 1193: 939 (peripheral zone (PZ)) and 254 (transition zone (TZ))). Thirty-seven percent of these lesions were sparse. Sparse lesions were primarily low-grade with the majority of PZ and 100 % of TZ sparse lesions ≤GS3 + 3/GG1. Dense lesions were significantly larger than sparse lesions in both PZ and TZ, p < 0.0001. On imaging, 246/45 PZ and 109/8 TZ dense/sparse 2D cancerous ROIs were drawn. Sparse GS3 + 3 and sparse ≥GS3 + 4 cancers did not have significantly different MRI intensities to dense GS3 + 3 cancers, while sparse GS3 + 3/GG1 cancers differed from benign, p < 0.05., Conclusion: Histopathologically identified prostate cancer lesions were sparse in 37 % of cases. Sparse cancers were entirely low grade in TZ and predominantly low-grade in PZ and generally small, thus likely posing lower risk for spread and progression than dense lesions. Sparse lesions were not distinguishable from dense lesions on mpMRI, but could be distinguished from benign tissues., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Prostate-specific membrane antigen (PSMA) is increasingly considered as a molecular target to achieve precision surgery for prostate cancer. A Delphi consensus was conducted to explore expert views in this emerging field and to identify knowledge and evidence gaps as well as unmet research needs that may help change practice and improve oncological outcomes for patients., Methods: One hundred and five statements (scored by a 9-point Likert scale) were distributed through SurveyMonkey®. Following evaluation, a consecutive second round was performed to evaluate consensus (16 statements; 89% response rate). Consensus was defined using the disagreement index, assessed by the research and development project/University of California, Los Angeles appropriateness method., Results: Eighty-six panel participants (72.1% clinician, 8.1% industry, 15.1% scientists, and 4.7% other) participated, most with a urological background (57.0%), followed by nuclear medicine (22.1%). Consensus was obtained on the following: (1) The diagnostic PSMA-ligand PET/CT should ideally be taken < 1 month before surgery, 1-3 months is acceptable; (2) a 16-20-h interval between injection of the tracer and surgery seems to be preferred; (3) PSMA targeting is most valuable for identification of nodal metastases; (4) gamma, fluorescence, and hybrid imaging are the preferred guidance technologies; and (5) randomized controlled clinical trials are required to define oncological value. Regarding surgical margin assessment, the view on the value of PSMA-targeted surgery was neutral or inconclusive. A high rate of "cannot answer" responses indicates further study is necessary to address knowledge gaps (e.g., Cerenkov or beta-emissions)., Conclusions: This Delphi consensus provides guidance for clinicians and researchers that implement or develop PSMA-targeted surgery technologies. Ultimately, however, the consensus should be backed by randomized clinical trial data before it may be implemented within the guidelines., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background Intravenous prostate-specific membrane antigen (PSMA)-targeted radioligand therapy improves survival in men with metastatic castration-resistant prostate cancer. Yet, the impact of selective prostatic arterial administration on primary tumor uptake is unclear. Purpose To compare gallium 68 ( 68 Ga)-PSMA-11 uptake using dynamic PET/CT in prostatic tumoral volumes of interest (VOIs) during intravenous and selective prostatic arterial infusions for individuals with untreated, high-risk prostate cancer. Materials and Methods In this prospective, intraindividual comparative study conducted at an academic medical center, five men aged 58, 61, 64, 66, and 68 years with treatment-naive prostate cancer were enrolled between January 2022 and February 2023 and underwent two dynamic 68 Ga-PSMA-11 PET/CT examinations 1 week apart. During the first examination, the radiotracer was administered intravenously. During the second administration, the radiotracer was delivered into either the right or left prostatic artery through an angiographically placed microcatheter. The primary outcome was maximum standardized uptake value (SUV max ) in prostatic tumoral VOIs. The secondary outcomes included mean SUV (SUV mean ) in prostatic tumoral VOIs and area under the SUV mean curves (AUC). Longitudinal mixed-effects models were used to compare dynamic SUV max and SUV mean time-activity curves (TACs), and paired t tests were used for the remaining data. Results The mean SUV max within tumoral VOIs was 14 (range, 3-43) for venous sessions and 938 (range, 460-1436) for arterial sessions ( P = .008). The SUV mean within VOIs was greater during arterial sessions ( P < .001) overall and 46-fold and 19-fold greater at peak uptake and final time points, respectively. The mean AUC was greater on arterial TACs than on venous TACs at 14600 SUV × min (range, 8353-20025 SUV × min) and 240 SUV × min (range, 69-622 SUV × min), respectively ( P = .002). Conclusion Selective prostatic arterial infusion resulted in greater 68 Ga-PSMA-11 tumoral SUV than intravenous infusion. Further study of local-regional, intra-arterial delivery of a PSMA-targeted theranostic agent is warranted in high-risk prostate cancer. ClinicalTrials.gov identifier: NCT04976257 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Civelek in this issue.

Background: Molecular-based risk classifier tests are increasingly being utilized by urologists and radiation oncologists to guide clinical decision making. The Decipher prostate biopsy test is a 22-gene RNA biomarker assay designed to predict likelihood of high-grade disease at radical prostatectomy and risk of metastasis and mortality. The test provides a risk category of low, intermediate, or high. We investigated histologic features of biopsies in which the Grade Group (GG) and Decipher risk category (molecular risk) were discrepant., Methods: Our institutional urologic outcomes database was searched for men who underwent prostate biopsies with subsequent Decipher testing from 2016 to 2020. We defined discrepant GG and molecular risk as either GG1-2 with high Decipher risk category or GG ≥ 3 with low Decipher risk category. The biopsy slide on which Decipher testing was performed was re-reviewed for GG and various histologic features, including % Gleason pattern 4, types of Gleason pattern 4 and 5, other "high risk" features (e.g., complex papillary, ductal carcinoma, intraductal carcinoma [IDC]), and other unusual and often "difficult to grade" patterns (e.g., atrophic carcinoma, mucin rupture, pseudohyperplastic carcinoma, collagenous fibroplasia, foamy gland carcinoma, carcinoma with basal cell marker expression, carcinoma with prominent vacuoles, and stromal reaction). Follow-up data was also obtained from the electronic medical record., Results: Of 178 men who underwent prostate biopsies and had Decipher testing performed, 41 (23%) had discrepant GG and molecular risk. Slides were available for review for 33/41 (80%). Of these 33 patients, 23 (70%) had GG1-2 (GG1 n = 5, GG2 n = 18) with high Decipher risk, and 10 (30%) had GG ≥ 3 with low Decipher risk. Of the 5 GG1 cases, one case was considered GG2 on re-review; no other high risk features were identified but each case showed at least one of the following "difficult to grade" patterns: 3 atrophic carcinoma, 1 collagenous fibroplasia, 1 carcinoma with mucin rupture, and 1 carcinoma with basal cell marker expression. Of the 18 GG2 high Decipher risk cases, 2 showed GG3 on re-review, 5 showed large cribriform and/or other high risk features, and 10 showed a "difficult to grade" pattern. Of the 10 GG ≥ 3 low Decipher risk cases, 5 had known high risk features including 2 with large cribriform, 1 with IDC, and 1 with Gleason pattern 5., Conclusions: In GG1-2 high Decipher risk cases, difficult to grade patterns were frequently seen in the absence of other known high risk morphologic features; whether these constitute true high risk cases requires further study. In the GG ≥ 3 low Decipher risk cases, aggressive histologic patterns such as large cribriform and IDC were observed in half (50%) of cases; therefore, the molecular classifier may not capture all high risk histologic patterns., (© 2024 The Authors. The Prostate published by Wiley Periodicals LLC.)

Background and Objective: Active surveillance (AS) of prostate cancer (PCa) involves regular monitoring for disease progression. The aim is to avoid unnecessary treatment while ensuring appropriate and timely treatment for those whose disease progresses. AS has emerged as the standard of care for low-grade (Gleason grade 1, GG 1) PCa. Opponents are concerned that initial undersampling and delay of definitive management for patients with GG 2 disease may lead to adverse outcomes. We sought to determine whether the timing for definitive management of GG 2 PCa, either upfront or after initial AS, affects recurrence outcomes after radical prostatectomy (RP)., Methods: Participants were diagnosed with cT1-2N0/xM0/x, prostate-specific antigen (PSA) <20 ng/ml, and GG 1-2 PCa between 2000 and 2020 and underwent immediate RP for GG 2 or AS followed by delayed RP on upgrading to GG 2. The outcome was recurrence-free survival (RFS) after surgery, with recurrence defined as either biochemical failure (2 PSA measurements ≥0.2 ng/ml) or a second treatment. Multivariable Cox proportional-hazards regression models were used to calculate associations between the timing for definitive RP and the risk of recurrence, adjusted for age at diagnosis, percentage of positive biopsy cores (PPC), PSA density, PSA before RP, year of diagnosis, surgical margins, genomic risk score, and prostate MRI findings., Key Findings: Of the 1259 men who met the inclusion criteria, 979 underwent immediate RP after diagnosis of GG 2, 190 underwent RP within 12 mo of upgrading to GG 2 on AS, and 90 men underwent RP >12 mo after upgrading to GG 2. The 5-yr RFS rates were 81% for the immediate RP group, 80% for the delayed RP ≤12 mo, and 70% for the delayed RP >12 mo group (univariate log-rank p = 0.03). Cox multivariable regression demonstrated no difference in RFS outcomes between immediate RP for GG 2 disease and delayed RP after upgrading on AS. PPC (hazard ratio [HR] per 10% increment 1.08, 95% confidence interval [CI] 1.02-1.15; p = 0.01) and PSA before RP (HR 1.06, 95% CI 1.03-1.09; p < 0.01) were significantly associated with the risk of recurrence., Conclusions and Clinical Implications: PPC and PSA before RP, but not the timing of definitive surgery after upgrade to GG 2, were associated with the risk of PCa recurrence after RP on multivariable analysis. These findings support the safety of AS and delayed definitive therapy for a subset of patients with GG 2 disease., Patient Summary: In a large group of 1259 patients with low-grade prostate cancer, we found that delaying surgical treatment after an initial period of active surveillance resulted in no differences in prostate cancer recurrence. Our results support the safety of active surveillance for low-grade prostate cancer., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Importance: Outcomes from protocol-directed active surveillance for favorable-risk prostate cancers are needed to support decision-making., Objective: To characterize the long-term oncological outcomes of patients receiving active surveillance in a multicenter, protocol-directed cohort., Design, Setting, and Participants: The Canary Prostate Active Surveillance Study (PASS) is a prospective cohort study initiated in 2008. A cohort of 2155 men with favorable-risk prostate cancer and no prior treatment were enrolled at 10 North American centers through August 2022., Exposure: Active surveillance for prostate cancer., Main Outcomes and Measures: Cumulative incidence of biopsy grade reclassification, treatment, metastasis, prostate cancer mortality, overall mortality, and recurrence after treatment in patients treated after the first or subsequent surveillance biopsies., Results: Among 2155 patients with localized prostate cancer, the median follow-up was 7.2 years, median age was 63 years, 83% were White, 7% were Black, 90% were diagnosed with grade group 1 cancer, and median prostate-specific antigen (PSA) was 5.2 ng/mL. Ten years after diagnosis, the incidence of biopsy grade reclassification and treatment were 43% (95% CI, 40%-45%) and 49% (95% CI, 47%-52%), respectively. There were 425 and 396 patients treated after confirmatory or subsequent surveillance biopsies (median of 1.5 and 4.6 years after diagnosis, respectively) and the 5-year rates of recurrence were 11% (95% CI, 7%-15%) and 8% (95% CI, 5%-11%), respectively. Progression to metastatic cancer occurred in 21 participants and there were 3 prostate cancer-related deaths. The estimated rates of metastasis or prostate cancer-specific mortality at 10 years after diagnosis were 1.4% (95% CI, 0.7%-2%) and 0.1% (95% CI, 0%-0.4%), respectively; overall mortality in the same time period was 5.1% (95% CI, 3.8%-6.4%)., Conclusions and Relevance: In this study, 10 years after diagnosis, 49% of men remained free of progression or treatment, less than 2% developed metastatic disease, and less than 1% died of their disease. Later progression and treatment during surveillance were not associated with worse outcomes. These results demonstrate active surveillance as an effective management strategy for patients diagnosed with favorable-risk prostate cancer.

Background: Active surveillance (AS) is standard care for most men with low-risk prostate cancer (PC); yet, many men on AS eventually undergo curative therapy. Interventions to lower the risk of cancer progression and fear of recurrence among men on AS for PC are needed., Objective: To determine the effect of aerobic exercise on cardiorespiratory fitness, body size, and quality of life (QOL) among men on AS for PC., Design, Setting, and Participants: We conducted a 1:1 randomized controlled trial among 51 men with low-risk PC who elected AS. Participants were enrolled at the University of California, San Francisco., Intervention: The 16-wk intervention included a home-based walking program with a nonlinear exercise prescription tailored to baseline fitness level, heart rate monitor, and weekly phone call with an exercise physiologist. Controls received printed materials., Outcome Measurements and Statistical Analysis: Cardiorespiratory fitness was measured using VO 2 peak; secondary outcomes included change in body size, anxiety, and QOL. Analyses were based on intention to treat., Results and Limitations: Between 2016 and 2021, we randomized 51 men to intervention (n = 26) or control (n = 25). Follow-up was 88% (45/51), 85% (22/26) in the intervention and 92% (23/25) in the control group. At 16 wk, the intervention group had a higher mean VO 2 peak than the control group (31.9 ± 4.7 vs 27.2 ± 4.8 ml/kg/min; group × time effect p value: <0.001). Additionally, the intervention group reported less fear of PC recurrence and urinary obstruction/irritation, while controls reported more of these two QOL measures, from 0 to 16 wk (p = 0.04 and 0.03, respectively). Two participants discontinued the intervention, including one due to knee pain related to the study., Conclusions: A home-based walking program improved VO 2 peak and reduced urinary obstruction/irritation and fear of recurrence among men on AS for PC., Patient Summary: Moderate to vigorous aerobic exercise improves fitness and quality of life among men on active surveillance for prostate cancer., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The optimal treatment of localized prostate cancer (PCa) remains controversial., Objective: To compare long-term survival among men who underwent radical prostatectomy (RP), brachytherapy (BT), external beam radiation therapy (EBRT), primary androgen deprivation therapy (PADT), or monitoring (active surveillance [AS]/watchful waiting [WW]) for PCa., Design, Setting, and Participants: This is a cohort study with long-term follow-up from the multicenter, prospective, largely community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Men with biopsy-proven, clinical T1-3aN0M0, localized PCa were consecutively accrued within 6 mo of diagnosis and had clinical risk data and at least 12 mo of follow-up after diagnosis available., Outcome Measurements and Statistical Analysis: PCa risk was assessed, and multivariable analyses were performed to compare PCa-specific mortality (PCSM) and all-cause mortality by primary treatment, with extensive adjustment for age and case mix using the Cancer of the Prostate Risk Assessment (CAPRA) score and a well-validated nomogram., Results and Limitations: Among 11 864 men, 6227 (53%) underwent RP, 1645 (14%) received BT, 1462 (12%) received EBRT, 1510 (13%) received PADT, and 1020 (9%) were managed with AS/WW. At a median of 9.4 yr (interquartile range 5.8-13.7) after treatment, 764 men had died from PCa. After adjusting for CAPRA score, the hazard ratios for PCSM with RP as the reference were 1.57 (95% confidence interval [CI] 1.24-1.98; p < 0.001) for BT, 1.55 (95% CI 1.26-1.91; p < 0.001) for EBRT, 2.36 (95% CI 1.94-2.87; p < 0.001) for PADT, and 1.76 (95% CI 1.30-2.40; p < 0.001) for AS/WW. In models for long-term outcomes, PCSM differences were negligible for low-risk disease and increased progressively with risk. Limitations include the evolution of diagnostic and therapeutic strategies for PCa over time. In this nonrandomized study, the possibility of residual confounding remains salient., Conclusions: In a large, prospective cohort of men with localized PCa, after adjustment for age and comorbidity, PCSM was lower after local therapy for those with higher-risk disease, and in particular after RP. Confirmation of these results via long-term follow-up of ongoing trials is awaited., Patient Summary: We evaluated different treatment options for localized prostate cancer in a large group of patients who were treated mostly in nonacademic medical centers. Results from nonrandomized trials should be interpret with caution, but even after careful risk adjustment, survival rates for men with higher-risk cancer appeared to be highest for patients whose first treatment was surgery rather than radiotherapy, hormones, or monitoring., (Copyright © 2023. Published by Elsevier B.V.)

Background: The gold standard for detecting bladder cancer is cystoscopy with biopsy or transurethral resection confirming histologic diagnosis. URO17® employs a chromogenically labeled monoclonal antibody to keratin 17 (k17), an intermediate filament cytoskeleton molecule associated with bladder, pancreatic, and cervical cancers. Preliminary studies evaluating k17 demonstrated a high sensitivity and specificity for the detection of bladder cancer, supporting the need for further study., Objective: To evaluate the sensitivity and specificity of URO17., Methods: This is a cross-sectional study of participants undergoing urologic procedures between July 6, 2018 and July 17, 2019 at a single institution. Patients undergoing cystectomy, endoscopic bladder and/or upper tract procedure for probable urothelial carcinoma comprised cases; patients undergoing urologic procedures for other reasons comprised the control group (i.e. prostatectomy, nephrectomy, etc.). Voided urine samples were at the time of procedure; a minority of participants underwent multiple resections in the study period, thus, as many as three urine samples were taken from any given participant. Samples were distributed for blinded testing with URO17. Sensitivity and specificity were calculated., Results: In 152 participants and 167 samples, URO17 demonstrated an overall sensitivity of 90% and 92% and a specificity of 88% and 87%, respectively. In 76 participants and 91 samples from patients with suspected urothelial carcinoma, the sensitivity was 90% and 92%, and the specificity was 50% and 54%, respectively. No controls demonstrated a positive URO17 result, and URO17 superseded urine cytology detection of low-grade and high-grade Ta. False positive results were associated with inflamed tissue or urothelial atypia on histology; the large majority had a history of intravesical therapy., Conclusion: Limitations include cross-sectional design and convenience sampling. URO17 may improve sensitivity of urine cytology in the detection of urothelial cancer, though further study is required to refine the application of this biomarker in clinical practice., Competing Interests: Declaration of competing interest SJ is co-founder, President, and COO of KDx diagnostics; NK is co-founder and CEO of KDx diagnostics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The challenge of distinguishing indolent from aggressive prostate cancer (PCa) complicates decision-making for men considering active surveillance (AS). Genomic classifiers (GCs) may improve risk stratification by predicting end points such as upgrading or upstaging (UG/US). The aim of this study was to assess the impact of GCs on UG/US risk prediction in a clinicopathologic model., Methods: Participants had favorable-risk PCa (cT1-2, prostate-specific antigen [PSA] ≤15 ng/mL, and Gleason grade group 1 [GG1]/low-volume GG2). A prediction model was developed for 864 men at the University of California, San Francisco, with standard clinical variables (cohort 1), and the model was validated for 2267 participants from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (cohort 2). Logistic regression was used to compute the area under the receiver operating characteristic curve (AUC) to develop a prediction model for UG/US at prostatectomy. A GC (Oncotype Dx Genomic Prostate Score [GPS] or Prolaris) was then assessed to improve risk prediction., Results: The prediction model included biopsy GG1 versus GG2 (odds ratio [OR], 5.83; 95% confidence interval [CI], 3.73-9.10); PSA (OR, 1.10; 95% CI, 1.01-1.20; per 1 ng/mL), percent positive cores (OR, 1.01; 95% CI, 1.01-1.02; per 1%), prostate volume (OR, 0.98; 95% CI, 0.97-0.99; per mL), and age (OR, 1.05; 95% CI, 1.02-1.07; per year), with AUC 0.70 (cohort 1) and AUC 0.69 (cohort 2). GPS was associated with UG/US (OR, 1.03; 95% CI, 1.01-1.06; p < .01) and AUC 0.72, which indicates a comparable performance to the prediction model., Conclusions: GCs did not substantially improve a clinical prediction model for UG/US, a short-term and imperfect surrogate for clinically relevant disease outcomes., (© 2024 American Cancer Society.)

Importance: Plant-based diets are associated with many health and environmental benefits, including primary prevention of fatal prostate cancer, but less is known about postdiagnostic plant-based diet patterns in individuals with prostate cancer., Objective: To examine whether postdiagnostic plant-based dietary patterns are associated with risk of prostate cancer progression and prostate cancer-specific mortality., Design, Setting, and Participants: This longitudinal observational cohort study included men with biopsy-proven nonmetastatic prostate cancer (stage ≤T3a) from the diet and lifestyle substudy within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) enrolled at 43 urology practices across the US from 1999 to 2018. Participants completed a comprehensive diet and lifestyle questionnaire (including a validated food frequency questionnaire [FFQ]) between 2004 and 2016. Data were analyzed from August 2022 to April 2023., Exposures: Overall plant-based diet index (PDI) and healthful plant-based diet index (hPDI) scores were calculated from the FFQ., Main Outcomes and Measures: The primary outcome was prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer-specific mortality). The secondary outcome was prostate cancer-specific mortality., Results: Among 2062 participants (median [IQR] age, 65.0 [59.0-70.0] years), 61 (3%) identified as African American, 3 (<1%) identified as American Indian or Alaska Native, 9 (<1%) identified as Asian or Pacific Islander, 15 (1%) identified as Latino, and 1959 (95%) identified as White. Median (IQR) time from prostate cancer diagnosis to FFQ was 31.3 (15.9-62.0) months after diagnosis. During a median (IQR) follow-up of 6.5 (1.3-12.8) years after the FFQ, 190 progression events and 61 prostate cancer-specific mortality events were observed. Men scoring in the highest vs lowest quintile of PDI had a 47% lower risk of progression (HR, 0.53; 95% CI, 0.37-0.74; P for trend = .003). The hPDI was not associated with risk of progression overall. However, among 680 individuals with Gleason grade 7 or higher at diagnosis, the highest hPDI quintile was associated with a 55% lower risk of progression compared with the lowest hPDI quintile (HR 0.45; 95% CI, 0.25-0.81; P for trend = .01); no association was observed in individuals with Gleason grade less than 7., Conclusions and Relevance: In this cohort study of 2062 men with prostate cancer, higher intake of plant foods after prostate cancer diagnosis was associated with lower risk of cancer progression. These findings suggest nutritional assessment and counseling may be recommended to patients with prostate cancer to help establish healthy dietary practices and support well-being and overall health.

Background: Prostate cancers featuring an expansile cribriform (EC) pattern are associated with worse clinical outcomes following radical prostatectomy (RP). However, studies of the genomic characteristics of Gleason pattern 4 subtypes are limited., Objective: To explore transcriptomic characteristics and heterogeneity within Gleason pattern 4 subtypes (fused/poorly formed, glomeruloid, small cribriform, EC/intraductal carcinoma [IDC]) and the association with biochemical recurrence (BCR)-free survival., Design, Setting, and Participants: This was a retrospective cohort study including 165 men with grade group 2-4 prostate cancer who underwent RP at a single academic institution (2016-2020) and Decipher testing of the RP specimen. Patients with Gleason pattern 5 were excluded. IDC and EC patterns were grouped. Median follow-up was 2.5 yr after RP for patients without BCR., Outcomes Measurements and Statistical Analysis: Prompted by heterogeneity within pattern 4 subtypes identified via exploratory analyses, we investigated transcriptomic consensus clusters using partitioning around medoids and hallmark gene set scores. The primary clinical outcome was BCR, defined as two consecutive prostate-specific antigen measurements >0.2 ng/ml at least 8 wk after RP, or any additional treatment. Multivariable Cox proportional-hazards models were used to determine factors associated with BCR-free survival., Results and Limitations: In this cohort, 99/165 patients (60%) had EC and 67 experienced BCR. Exploratory analyses and clustering demonstrated transcriptomic heterogeneity within each Gleason pattern 4 subtype. In the multivariable model controlled for pattern 4 subtype, margin status, Cancer of the Prostate Risk Assessment Post-Surgical score, and Decipher score, a newly identified steroid hormone-driven cluster (hazard ratio 2.35 95% confidence interval 1.01-5.47) was associated with worse BCR-free survival. The study is limited by intermediate follow-up, no validation cohort, and lack of accounting for intratumoral and intraprostatic heterogeneity., Conclusions: Transcriptomic heterogeneity was present within and across each Gleason pattern 4 subtype, demonstrating there is additional biologic diversity not captured by histologic subtypes. This heterogeneity can be used to develop novel signatures and to classify transcriptomic subtypes, which may help in refining risk stratification following RP to further guide decision-making on adjuvant and salvage treatments., Patient Summary: We studied prostatectomy specimens and found that tumors with similar microscopic appearance can have genetic differences that may help to predict outcomes after prostatectomy for prostate cancer. Our results demonstrate that further gene expression analysis of prostate cancer subtypes may improve risk stratification after prostatectomy. Future studies are needed to develop novel gene expression signatures and validate these findings in independent sets of patients., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Aims: A recent outcome-based, radical prostatectomy study defined > 0.25 mm diameter to distinguish large versus small cribriform glands, with > 0.25 mm associated with worse recurrence-free survival. This study evaluates whether identification of > 0.25 mm cribriform glands in Grade Group 2 patients at biopsy is associated with adverse pathology at radical prostatectomy., Methods and Results: Tumours containing biopsy slides for 133 patients with Grade Group 2 prostate cancer with subsequent radical prostatectomy were re-reviewed for large cribriform glands (diameter > 0.25 mm). The primary outcome was adverse pathology (Grade Groups 3-5; stage pT3a or greater, or pN1). The secondary outcome was recurrence-free survival. Cribriform pattern was present in 52 of 133 (39%) patients; of these, 16 of 52 (31%) had large cribriform glands and 36 of 52 (69%) had only small cribriform glands. Patients with large cribriform glands had significantly more adverse pathology at radical prostatectomy compared to patients with small cribriform glands and no cribriform glands (large = 11 of 16, 69%; small = 12 of 36, 33%; no cribriform = 25 of 81, 31%; χ 2 P-value 0.01). On multivariate analysis, large cribriform glands were also associated with adverse pathology, independent of age, prostate-specific antigen (PSA)/PSA density at diagnosis, year of diagnosis and biopsy cores percentage positive (global P-value 0.02). Large cribriform glands were also associated with increased CAPRA-S surgical risk score (Kruskal-Wallis P-value 0.02)., Conclusions: Large cribriform glands using a diameter > 0.25 mm definition in Grade Group 2 patients on biopsy are associated with increased risk of adverse pathology at radical prostatectomy. The presence of large cribriform histology should be considered when offering active surveillance for those with Grade Group 2 disease., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Background: Men with high-risk prostate cancer undergoing surgery likely recur due to failure to completely excise regional and/or local disease., Objective: The first-in-human evaluation of safety, pharmacokinetics, and exploratory efficacy of IS-002, a novel near-infrared prostate-specific membrane antigen (PSMA)-targeted fluorescence imaging agent, designed for intraoperative prostate cancer visualization., Design, Setting, and Participants: A phase 1, single-center, dose-escalation study was conducted in 24 men with high-risk prostate cancer scheduled for robotic-assisted radical prostatectomy with (extended) pelvic lymph node dissection using the da Vinci surgical system., Outcome Measurements and Statistical Analysis: Adverse events (AEs), vital signs, complete blood count, complete metabolic panel, urinalysis, and electrocardiogram were assessed over a 14-d period and compared with baseline. The pharmacokinetic profile of IS-002 was determined. Diagnostic accuracy was assessed for exploratory efficacy., Results and Limitations: AEs predominantly included discoloration of urine (n = 22/24; expected, related, grade 1). There were no grade ≥2 AEs. IS-002 C max and area under the curve increased with increasing dose. Plasma concentrations declined rapidly in a biphasic manner, with the median terminal half-lives ranging from 5.0 to 7.6 h, independent of dose and renal function. At 25 μg/kg, the exploratory efficacy readouts for the negative and positive predictive values were, 97% and 45% for lymph nodes, and 100% and 80% for residual/locoregional disease detection, respectively., Conclusions: IS-002 is safe and well tolerated, and has the potential to enable intraoperative tumor detection that could not be identified using standard imaging., Patient Summary: IS-002 is a new imaging agent that specifically targets the prostate-specific membrane antigen receptor. In this study, we tested IS-002 for the first time in men with high-risk prostate cancer undergoing surgery and found that IS-002 is safe, is cleared from the body quickly, and potentially allows identification of prostate cancer in areas that would not be identified by conventional white light imaging., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Distinguishing indolent from clinically significant localized prostate cancer is a major clinical challenge and influences clinical decision-making between treatment and active surveillance. The development of novel predictive biomarkers will help with risk stratification, and clinical decision-making, leading to a decrease in over or under-treatment of patients with prostate cancer. Here, we report that Trop2 is a prognostic tissue biomarker for clinically significant prostate cancer by utilizing the Canary Prostate Cancer Tissue Microarray (CPCTA) cohort composed of over 1100 patients from a multi-institutional study. We demonstrate that elevated Trop2 expression is correlated with worse clinical features including Gleason score, age, and pre-operative PSA levels. More importantly, we demonstrate that elevated Trop2 expression at radical prostatectomy predicts worse overall survival in men undergoing radical prostatectomy. Additionally, we detect shed Trop2 in urine from men with clinically significant prostate cancer. Our study identifies Trop2 as a novel tissue prognostic biomarker and a candidate non-invasive marker for prostate cancer., (© 2024. The Author(s).)

Background: Up to 40% of patients with prostate cancer may develop biochemical recurrence after surgery, with salvage radiation therapy (SRT) being the only curative option. In 2016, Tendulkar et al. (Contemporary update of a multi-institutional predictive nomogram for salvage radiotherapy after radical prostatectomy. J Clin Oncol 2016;34:3648-54) published a nomogram to predict distant metastasis in a cohort of patients treated with SRT with pre-SRT prostate-specific antigen (PSA) of 0.5 ng/ml after radical prostatectomy. In modern practice, SRT is delivered at lower PSA values., Objective: To train and externally validate a machine learning model to predict the risk of distant metastasis at 5 yr in a contemporary cohort of patients receiving SRT., Design, Setting, and Participants: We trained a machine learning model on data from 2418 patients treated with SRT at one institution, with a median PSA value of 0.27 ng/ml. External validation was done in 475 patients treated at two different institutions. Patients with cM1, pN1, or pT4 disease were excluded, as were patients with PSA >2 ng/ml or PSA 0, and patients with radiation dose <60 or ≥80 Gy., Outcome Measurements and Statistical Analysis: Model performance was assessed using calibration and time-dependent area under the receiver operating curve (tAUC)., Results and Limitations: Our model had better calibration and showed improved discrimination (tAUC = 0.72) compared with the Tendulkar model (tAUC = 0.60, p < 0.001). The main limitations of this study are its retrospective design and lack of validation on patients who received hormone therapy., Conclusions: The updated model can be used to provide more individualized risk assessments to patients treated with SRT at low PSA values, improving decision-making., Patient Summary: Up to 40% of patients with prostate cancer may develop biochemical recurrence after surgery, with salvage radiation therapy as the only potentially curative option. We trained and validated a machine learning model using clinical and surgical data to predict a patient's risk of distant metastasis at 5 yr after treatment. Our model outperformed the reference tool and can improve clinical decision-making by providing more personalized risk assessment., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Patients diagnosed with low-risk prostate cancer (PCa) are confronted with a difficult decision regarding whether to undergo definitive treatment or to pursue an active surveillance protocol. This is potentially further complicated by the possibility that patients and physicians may place different value on factors that influence this decision. We conducted a qualitative investigation to better understand patient and physician perceptions of factors influencing treatment decisions for low-risk PCa., Methods: Semi-structured interviews were conducted among 43 racially and ethnically diverse patients diagnosed with low-risk PCa, who were identified through a population-based cancer registry, and 15 physicians who were selected to represent a variety of practice settings in the Greater San Francisco Bay Area., Results: Patients and physicians both described several key individual (e.g., clinical) and interpersonal (e.g., healthcare communications) factors as important for treatment decision-making. Overall, physicians' perceptions largely mirrored patients' perceptions. First, we observed differences in treatment preferences by age and stage of life. At older ages, there was a preference for less invasive options. However, at younger ages, we found varying opinions among both patients and physicians. Second, patients and physicians both described concerns about side effects including physical functioning and non-physical considerations. Third, we observed differences in expectations and the level of difficulty for clinical conversations based on information needs and resources between patients and physicians. Finally, we discovered that patients and physicians perceived patients' prior knowledge and the support of family/friends as facilitators of clinical conversations., Conclusions: Our study suggests that the gap between patient and physician perceptions on the influence of clinical and communication factors on treatment decision-making is not large. The consensus we observed points to the importance of developing relevant clinical communication roadmaps as well as high quality and accessible patient education materials., (© 2023. The Author(s).)

Introduction: Men with a detectable PSA after radical prostatectomy (RP) are often offered salvage therapy while those with an undetectable PSA are monitored. We aim to better characterize the natural history of men with an initially undetectable PSA who subsequently developed a detectable PSA > 6 months after RP., Methods: Retrospective analysis of men who underwent RP for clinically localized prostate cancer at the University of California, San Francisco from 2000 to 2022. The primary outcome was biochemical recurrence, defined as 2 consecutive PSA > = 0.03 ng/mL starting 6 months after surgery. Secondary outcomes were salvage treatment, post-salvage treatment, metastasis free survival (MFS), prostate cancer specific mortality (PCSM), and all-cause mortality (ACM). This cohort was compared to a previously described cohort who had an immediately detectable post-operative PSA., Results: From our cohort of 3348 patients, we identified 2868 men who had an undetectable post-op PSA. Subsequently, 642 men had a delayed detectable PSA at a median of 25 months (IQR 15, 43) with median follow-up of 72 months after RP. PSA at time of failure was <0.10 ng/mL for 65.7% of men. Of those with a delayed detectable PSA, 46% underwent salvage treatment within 10 years after RP at a median PSA of 0.08 ng/mL (IQR 0.05, 0.14). High CAPRA-S score (HR 1.09, CI 1.02-1.17, p = 0.02) and PSA doubling time (PSA-DT) of <6 months (HR 7.58, CI 5.42-10.6, p < 0.01) were associated with receiving salvage treatment. After salvage treatment, 62% of men had recurrent PSA failure within 10 years. Overall, MFS was 92%, PCSM 3%, and ACM 6% at 10 years. For those who received tertiary treatment for recurrent PSA failure, MFS was 54%, PCSM 23% and ACM 23% at 10 years' time., Conclusions: Men who develop a detectable PSA > 6 months post-operatively may have excellent long-term outcomes, even in the absence of salvage therapy., (© 2023. The Author(s).)

Objective: To understand the relationship between common urologic medications phosphodiesterase-5 inhibitors (PDE5i) and anticholinergics (AC) and risk of dementia onset in men who underwent different primary treatments for prostate cancer., Materials and Methods: Patients (>50years) with prostate cancer (1998-2022) without Alzheimer's disease or related dementias were selected from Cancer of the Prostatic Strategic Urologic Research Endeavor Registry. Minimum medication use was 3months. Fine-Gray regression was performed to determine the association between medication exposure and dementia onset ≥12months after primary treatment in men matched on age, race, comorbid conditions, smoking, and type of clinical site, with competing risk of death., Results: Among 5937 men (53% PDE5i; 14% AC), PDE5i users were younger (63 vs 70, P < .01) with less CAD, CVA, DM (all P < .01); AC users were older (68 vs 66, P < .01) with higher incidence of comorbidities (P < .01). Median months of use was 24.3 (IQR 12.1, 48.7) for PDE5i and 12.2 (IQR 6.1, 24.3) for AC users. Cumulative incidence of Alzheimer's disease or related dementias was 6.5% at 15years. PDE5i (P = .07) and AC (P = .06) were not associated with dementia regardless of primary treatment modality., Conclusion: In this retrospective cohort study, PDE5i and AC use do not appear independently associated with risk of dementia. Notably, our cohort was generally healthy and younger which may limit our ability to detect significance. We recommend prospective investigation into association between PDE5i and dementia and advise continued judicious stewardship of AC in older patient populations., Competing Interests: Declaration of Competing Interest No conflict., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Contemporary treatment strategies for localized prostate cancer (PCa) have been evolved over time. However, there is little data regarding survival outcomes based on initial treatment by risk group in this new era. This study aims to evaluate survival outcomes among men who underwent observation, radiotherapy, or radical prostatectomy for localized PCa using a population-based cohort., Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) prostate with watchful waiting dataset (2010-2016) was used. We included men diagnosed with localized PCa and clinical stage T1c-2cN0M0. Other inclusion criteria were age 50-79 years, prostate-specific antigen (PSA) ≤50 ng/mL, and initial treatment with observation (active surveillance/watchful waiting), radiotherapy, or radical prostatectomy. PCa risk was assessed using the D'Amico classification. The primary endpoint was overall survival. Secondary endpoints included PCa-specific survival. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression and competing risk analysis were performed to assess outcomes., Results: After IPTW-adjusting, pseudo-population comprised 521,656 men (observation: 170,428, radiotherapy: 175,628, radical prostatectomy: 175,600) at a median 36.5 month follow-up. Observation demonstrated the lowest 5-year overall survival rate (91.6%) after IPTW-adjusting in comparison to radiotherapy (92.4%) and radical prostatectomy (96.1%, p<0.001). Men who underwent radical prostatectomy had the lowest cumulative PCa-specific and all-cause mortality (p<0.001). Compared to observation, radiotherapy (sub-distribution hazard ratio [sHR], 0.89; 95% CI, 0.81-0.97; p=0.012) and radical prostatectomy (sHR, 0.46; 95% CI, 0.41-0.52; p<.001) had a lower risk of PCa-specific mortality in competing risk analysis after adjustment for all other factors and other-cause death., Conclusions: Intermediate-term mortality risk in men with localized PCa were lower with active treatments compared to observation-especially for intermediate- and high-risk disease. However, observation represents a safe management strategy in men within the low-risk group., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Phosphatase and tensin homolog (PTEN) loss is associated with adverse outcomes in prostate cancer and can be measured via immunohistochemistry. The purpose of the study was to establish the clinical application of an in-house developed artificial intelligence (AI) image analysis workflow for automated detection of PTEN loss on digital images for identifying patients at risk of early recurrence and metastasis. Postsurgical tissue microarray sections from the Canary Foundation (n = 1264) stained with anti-PTEN antibody were evaluated independently by pathologist conventional visual scoring (cPTEN) and an automated AI-based image analysis pipeline (AI-PTEN). The relationship of PTEN evaluation methods with cancer recurrence and metastasis was analyzed using multivariable Cox proportional hazard and decision curve models. Both cPTEN scoring by the pathologist and quantification of PTEN loss by AI (high-risk AI-qPTEN) were significantly associated with shorter metastasis-free survival (MFS) in univariable analysis (cPTEN hazard ratio [HR], 1.54; CI, 1.07-2.21; P = .019; AI-qPTEN HR, 2.55; CI, 1.83-3.56; P < .001). In multivariable analyses, AI-qPTEN showed a statistically significant association with shorter MFS (HR, 2.17; CI, 1.49-3.17; P < .001) and recurrence-free survival (HR, 1.36; CI, 1.06-1.75; P = .016) when adjusting for relevant postsurgical clinical nomogram (Cancer of the Prostate Risk Assessment [CAPRA] postsurgical score [CAPRA-S]), whereas cPTEN does not show a statistically significant association (HR, 1.33; CI, 0.89-2; P = .2 and HR, 1.26; CI, 0.99-1.62; P = .063, respectively) when adjusting for CAPRA-S risk stratification. More importantly, AI-qPTEN was associated with shorter MFS in patients with favorable pathological stage and negative surgical margins (HR, 2.72; CI, 1.46-5.06; P = .002). Workflow also demonstrated enhanced clinical utility in decision curve analysis, more accurately identifying men who might benefit from adjuvant therapy postsurgery. This study demonstrates the clinical value of an affordable and fully automated AI-powered PTEN assessment for evaluating the risk of developing metastasis or disease recurrence after radical prostatectomy. Adding the AI-qPTEN assessment workflow to clinical variables may affect postoperative surveillance or management options, particularly in low-risk patients., (Copyright © 2023 United States & Canadian Academy of Pathology. All rights reserved.)

Background: Pelvic lymph node dissection (PLND) is the gold standard for diagnosis of lymph node involvement (LNI) in patients with prostate cancer. The Roach formula, Memorial Sloan Kettering Cancer Center (MSKCC) calculator, and Briganti 2012 nomogram are elegant and simple traditional tools used to estimate the risk of LNI and select patients for PLND., Objective: To determine whether machine learning (ML) can improve patient selection and outperform currently available tools for predicting LNI using similar readily available clinicopathologic variables., Design, Setting, and Participants: Retrospective data for patients treated with surgery and PLND between 1990 and 2020 in two academic institutions were used., Outcome Measurements and Statistical Analysis: We trained three models (two logistic regression models and one gradient-boosted trees-based model [XGBoost]) on data provided from one institution (n = 20267) with age, prostate-specific antigen (PSA) levels, clinical T stage, percentage positive cores, and Gleason scores as inputs. We externally validated these models using data from another institution (n = 1322) and compared their performance to that of the traditional models using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA)., Results and Limitations: LNI was present in 2563 patients (11.9%) overall, and in 119 patients (9%) in the validation data set. XGBoost had the best performance among all the models. On external validation, its AUC outperformed that of the Roach formula by 0.08 (95% confidence interval [CI] 0.042-0.12), the MSKCC nomogram by 0.05 (95% CI 0.016-0.070), and the Briganti nomogram by 0.03 (95% CI 0.0092-0.051; all p < 0.05). It also had better calibration and clinical utility in terms of net benefit on DCA across relevant clinical thresholds. The main limitation of the study is its retrospective design., Conclusions: Taking all measures of performance together, ML using standard clinicopathologic variables outperforms traditional tools in predicting LNI., Patient Summary: Determining the risk of cancer spread to the lymph nodes in patients with prostate cancer allows surgeons to perform lymph node dissection only in patients who need it and avoid the side effects of the procedure in those who do not. In this study, we used machine learning to develop a new calculator to predict the risk of lymph node involvement that outperformed traditional tools currently used by oncologists., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: To report objective long-term complications and health related quality of life (HRQOL) outcomes after radical prostatectomy (RP) with and without radiation therapy (RT) for prostate cancer (CaP)., Methods: We analyzed patients diagnosed with CaP who underwent RP from the UCSF Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry between 1995 and 2020. Cox proportional hazards were used to assess risk of postoperative complications which included cystitis, gastrointestinal (GI) toxicity, incontinence requiring a surgical procedure, ureteral injury and urinary stricture. Repeated measures mixed models were used to assess the effects of radiation and complications on patient-reported urinary, bowel, and sexual function after surgery., Results: Of 6,258 men who underwent RP, cumulative incidence of EBRT was 9.1% at 5 years after surgery. Patients who received postoperative radiation were at increased risk for onset of cystitis (HR 5.60, 95% CI 3.40-9.22, P < 0.01). Receipt of RT was not associated with other complications. In repeated measures analysis, postoperative RT was associated with worsening general health scores, adjusting for complications of incontinence, urinary stricture, GI toxicity or ureteral injury, independent of whether patients had those complications., Conclusions: RT after RP was associated with an increase in the risk of cystitis and worse general health in the long term. Other complications and HRQOL outcomes did not demonstrate differences by whether patients had RT or not. While post-operative RT is the only curative option for CaP after RP, patients and providers should be aware of the increased risks when making treatment decisions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To characterize the incidence of stress urinary incontinence (SUI) after radical prostatectomy (RP), its treatment, and impact on quality of life (QoL) and work status 1year after RP., Materials and Methods: Prostate cancer patients treated by RP (1998-2016) were selected from CaPSURE. SUI was defined as any pads per day (ppd) 1 year after RP. SUI procedures were tracked by CPT codes (sling and artificial sphincter). Patients reported work status (full-time, part-time, unpaid), UCLA PCa Index urinary function (UF) and bother (UB) and SF36 Index physical function (PF). Associations of incontinence with UF, UB, and PF and work status changes were assessed (ANOVA). Lifetable estimates and Cox proportional hazards regression evaluated risk of undergoing SUI procedures., Results: 664/2989 (22%) men treated with RP reported SUI at 1 year. More men with SUI had ≥GG2, intermediate to high-risk disease and non-nerve-sparing surgery (all P < .01). Cumulative incidence of SUI procedures was 1.4% at 10years after RP. Age (HR 2.68 per 10years, 95% CI 1.41-5.08) and number of ppd at 1 year (HR 3.20, 95% CI 2.27-4.50) were associated with undergoing SUI procedures. UF declined at 1year after RP, while UB and PF remained stable. UF, UB, and PF were inversely associated with number of ppd (all P < .01). Change in work status was not associated with incontinence or QoL scores., Conclusion: Incontinence affected QoL without impacting work status, suggesting that men with SUI after RP may continue working and go under-treated despite impact on QoL., Competing Interests: Declaration of Competing Interest Peter R. Carroll, MD MPH - Source of Funding (UCSF Goldberg-Benioff Program in Translational Cancer Biology). All the other authors have no conflict of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: We aim to characterize the magnitude of the work burden (weeks off from work) associated with prostate cancer (PCa) treatment over a 10-year period after PCa diagnosis and identify those at greatest risk., Materials and Methods: We identified men diagnosed with PCa treated with radical prostatectomy, radiation therapy, or active surveillance/watchful waiting within CaPSURE. Patients self-reported work burden and SF36 general health scores via surveys before and 1,3,5, and 10 years after treatment. Using multivariate repeated measures generalized estimating equation modeling we examined the association between primary treatment with risk of any work weeks lost due to care., Results: In total, 6693 men were included. The majority were White (81%, 5% Black, and 14% Other) with CAPRA low- (60%) or intermediate-risk (32%) disease and underwent surgery (62%) compared to 29% radiation and 9% active surveillance. Compared to other treatments, surgical patients were more likely to report greater than 7 days off work in the first year, with relatively less time off over time. Black men (RR 0.64, 95% CI 0.54-0.77) and those undergoing radiation (vs. surgery, RR 0.46, 95% CI 0.41-0.51) were less likely to report time off from work over time. Mean baseline GH score (73 [SD 18]) was similar between race and treatment groups, and stable over time., Conclusions: The work burden of cancer care continued up to 10 years after treatment and varied across racial groups and primary treatment groups, highlighting the multifactorial nature of this issue and the call to leverage greater resources for those at greatest risk., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Although official T-staging criteria for prostate cancer are based on digital rectal examination findings, providers increasingly rely on transrectal US and MRI to define pragmatic clinical stage to guide management. We assessed the impact of incorporating imaging findings into T-staging on performance of a well-validated prognostic instrument., Materials and Methods: Patients who underwent radical prostatectomy for prostate cancer diagnosed between 2000 and 2019 with stage ≤cT3a on both digital rectal examination and imaging (transrectal US/MRI) were included. The University of California, San Francisco CAPRA (Cancer of the Prostate Risk Assessment) score was computed 2 ways: (1) incorporating digital rectal examination-based T stage and (2) incorporating imaging-based T stage. We assessed for risk changes across the 2 methods and associations of CAPRA (by both methods) with biochemical recurrence, using unadjusted and adjusted Cox proportional hazards models. Model discrimination and net benefit were assessed with time-dependent area under the curve and decision curve analysis, respectively., Results: Of 2,222 men included, 377 (17%) increased in CAPRA score with imaging-based staging ( P < .01). Digital rectal examination-based (HR 1.54; 95% CI 1.48-1.61) and imaging-based (HR 1.52; 95% CI 1.46-1.58) CAPRA scores were comparably accurate for predicting recurrence with similar discrimination and decision curve analyses. On multivariable Cox regression, positive digital rectal examination at diagnosis (HR 1.29; 95% CI 1.09-1.53) and imaging-based clinical T3/4 disease (HR 1.72; 95% CI 1.43-2.07) were independently associated with biochemical recurrence., Conclusions: The CAPRA score remains accurate whether determined using imaging-based staging or digital rectal examination-based staging, with relatively minor discrepancies and similar associations with biochemical recurrence. Staging information from either modality can be used in the CAPRA score calculation and still reliably predict risk of biochemical recurrence.

Objective: To assess the long-term incidence of treatment-related toxicities and quality of life (QOL) outcomes associated with toxicity after external beam radiotherapy (EBRT) for prostate cancer., Methods: We identified all men who had EBRT between 1994 and 2017 from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a longitudinal, nationwide prostate cancer registry. CaPSURE was queried for patient-reported and International Classification of Diseases-9/10 and Current Procedural Terminology codes. The Medical Outcomes Studies Short Form 36 and the University of California, Los Angeles Prostate Cancer Index were used to provide measures of general health, sexual, urinary, and bowel function. Repeated measures mixed models were used to determine QOL change after onset of toxicity., Results: From a total of 15,332, 1744 (11.4%) men had EBRT. The median follow-up was 7.9years (interquartile range [IQR] 4.3-12.7). The median time to onset of any toxicity including urinary pad usage in 265 (15.4% at 8years) men was 4.3years (IQR 1.8-8.0). The most frequent toxicity was hemorrhagic cystitis (104, 5.9% at 8years) after a median of 3.7years (1.3-7.8), gastrointestinal (48, 2.7% at 8years) after a median of 4.2years (IQR 1.3-7.8), followed by urethral stricture (47, 2.4% at 8years) after a median of 3.7years (IQR 1.9-9.1). Repeated measures mixed models found that onset of hemorrhagic cystitis was associated with change in general health over time., Conclusion: EBRT for prostate cancer is associated with distinct treatment-related toxicities which can occur many years after treatment and can affect QOL. These results may help men understand the long-term implications of treatment decisions., Competing Interests: DECLARATION OF COMPETING INTEREST The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Although there are several decision aids for the treatment of localized prostate cancer (PCa), there are limitations in the consistency and certainty of the information provided. We aimed to better understand the treatment decision process and develop a decision-predicting model considering oncologic, demographic, socioeconomic, and geographic factors. Men newly diagnosed with localized PCa between 2010 and 2015 from the Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting database were included (n = 255,837). We designed two prediction models: (1) Active surveillance/watchful waiting (AS/WW), radical prostatectomy (RP), and radiation therapy (RT) decision prediction in the entire cohort. (2) Prediction of AS/WW decisions in the low-risk cohort. The discrimination of the model was evaluated using the multiclass area under the curve (AUC). A plausible Shapley additive explanations value was used to explain the model's prediction results. Oncological variables affected the RP decisions most, whereas RT was highly affected by geographic factors. The dependence plot depicted the feature interactions in reaching a treatment decision. The decision predicting model achieved an overall multiclass AUC of 0.77, whereas 0.74 was confirmed for the low-risk model. Using a large population-based real-world database, we unraveled the complex decision-making process and visualized nonlinear feature interactions in localized PCa., (© 2023. The Author(s).)

Purpose: Exercise and healthy diet are key components of cancer survivorship. We sought to explore perceived barriers to engaging in healthy diet and exercise, and whether these barriers change throughout remote-based behavioral interventions., Methods: Smart Pace (SP) and Prostate 8 (P8) were two 12-week pilot randomized controlled trials (RCTs) among 42 colorectal cancer (CRC) survivors and 76 prostate cancer (PC) survivors, respectively, that encouraged participants to implement exercise (both) and healthy diet (P8 only) through text messaging and wearable fitness monitors; P8 also included web materials. Participants completed surveys on perceived barriers and confidence in their ability to implement healthy behaviors at enrollment and 12 weeks; P8 also included a 52-week assessment., Results: At enrollment, CRC survivors commonly reported a lack of discipline/willpower (36%), time (33%), and energy (31%); PC survivors often reported a lack of knowledge about healthy dietary behaviors (26%). Not having anyone with whom to exercise with was a common barrier among both groups (21% in CRC, 20% in PC). Among the intervention groups in both studies, various enrollment barriers (overall, functional/psychological disability, aversiveness, excuses, and inconveniences) were associated with change in behavior over time., Conclusions: Among CRC and PC survivors, there are multiple potential barriers related to motivation, time, social support, and lack of knowledge, that can be addressed and overcome to improve healthy behaviors. Tailoring lifestyle interventions to participants' individual barriers and confidence is needed to promote and sustain behavior change long-term., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The morbidity and mortality conference is essential to medical education and quality improvement. Ideally, the conference is inclusive, judgment-free, and focused on practice improvement. In reality, it may not meet these goals. We reimagined the process by standardizing presentations and creating an oversight committee to improve the perceived value of the conference and identify opportunities for improvement. This study evaluates the subjective impact of the redesigned process at our institution and provides a blueprint for our reproducible model., Methods: We created a faculty and resident committee to review all submitted cases, implemented a standardized presentation template and moderating structure, and tracked quality improvement measures from proposed improvement initiatives. Attitudes toward the conference, including perceived quality/relevance, identification of potential systems changes, inclusiveness, and educational value, were assessed among faculty and trainees using pre- and postintervention Likert-style surveys., Results: Of 45 eligible department members, 41 (91%) completed the preintervention and 36 (80%) completed the postintervention survey. We found a statistically significant improvement in all questions between pre- and postintervention surveys except on the question about the conference environment being nonthreatening, which also improved but was not statistically significant. The overall average answer improved on the postintervention survey compared to the preintervention survey (3.36 vs 4.20, P < .001). These trends were similar regardless of attendee role and gender., Conclusions: Redesigning and standardizing the morbidity and mortality conference with greater attention to education, inclusion, systems change, and quality improvement improves the attitudes of conference attendees and increases the perceived value of the conference.

Introduction: Understanding what the most effective and safe non-steroidal anti-inflammatory drug (NSAID) is for managing osteoarthritis (OA) is complicated. OA is prevalent worldwide and people living with OA commonly have multiple comorbidities. The efficacy and safety of NSAIDs in a patient are influenced by their intrinsic and extrinsic factors. Current guidelines recommend the lowest dose for the shortest duration, monitoring patients for risk factors and comorbidities but generally do not specify, which NSAID is most suitable for a patient with specific comorbidities., Areas Covered: This paper looks at the mechanism of action of all NSAIDs and reviews the current literature concerning their safety in patients with and without comorbidities. Relevant publications were identified by searching PubMed and Cochrane Library using key terms. The search was conducted from inception to 18 July 2023 and included results published before 18 July 2023. The search results and their references were then manually reviewed., Expert Opinion: In the paper, we determine whether the current practice of 'lowest dose for shortest duration' is in fact the best approach for prescribing NSAIDs and identify which NSAIDs are most suitable given a patient's risk factors and comorbidities. Our aim is to help guide health professionals in recommending the most suitable NSAID for each patient.

Introduction: The University of California, San Francisco Cancer of the Prostate Risk Assessment (CAPRA) score is a validated tool using factors at diagnosis to predict prostate cancer outcomes after radical prostatectomy (RP). This study evaluates whether substitution of prostate-specific antigen (PSA) density for serum PSA improves predictive performance of the clinical CAPRA model., Methods: Participants were diagnosed in 2000-2019 with stage T1/T2 cancer, underwent RP, with at least a 6-month follow-up. We computed standard CAPRA score using diagnostic age, Gleason grade, percent positive cores, clinical T stage, and serum PSA, and an alternate score using similar variables but substituting PSA density for PSA. We reported CAPRA categories as low (0-2), intermediate (3-5), and high (6-10) risk. Recurrence was defined as two consecutive PSA ≥ 0.2 ng/mL or receipt of salvage treatment. Life table and Kaplan-Meier analysis evaluated recurrence-free survival after prostatectomy. Cox proportional hazards regression models tested associations of standard or alternate CAPRA variables with recurrence risk. Additional models tested associations between standard or alternate CAPRA score with recurrence risk. Cox log-likelihood ratio test (-2 LOG L) assessed model accuracy., Results: A total of 2880 patients had median age 62 years, GG1 30% and GG2 31%, median PSA 6.5, and median PSA density 0.19. Median postoperative follow-up was 45 months. Alternate CAPRA model was associated with shifts in risk scores, with 16% of patients increasing and 7% decreasing (p < 0.01). Recurrence-free survival after RP was 75% at 5 years and 62% at 10 years. Both CAPRA component models were associated with recurrence risk after RP on Cox regression. Covariate fit statistics showed better fit for standard CAPRA model versus alternate (p < 0.01). Standard (hazard ratio [HR]: 1.55; 95% confidence interval [CI]: 1.50-1.61) and alternate (HR: 1.50; 95% CI: 1.44-1.55) CAPRA scores were associated with recurrence risk, with better fit for standard model (p < 0.01)., Conclusions: In a 2880 patient cohort followed for median 45 months after RP, alternate CAPRA model using PSA density was associated with higher biochemical recurrence (BCR) risk, but performed inferior to standard CAPRA at predicting BCR. While PSA density is an established prognostic variable in prediagnostic settings and sub-stratifying low-risk disease, it does not improve BCR model predictive accuracy when applied across a range of cancer risk., (© 2023 Wiley Periodicals LLC.)

Although the American Urological Association recently dropped the very low-risk (VLR) subcategory for low-risk prostate cancer (PCa) and the European Association of Urology does not substratify low-risk PCa, the National Comprehensive Cancer Network (NCCN) guidelines still maintain this stratum, which is based on the number of positive biopsy cores, tumor extent in each core, and prostate-specific antigen density. This subdivision may be less applicable in the modern era in which imaging-targeted prostate biopsies are common practice. In our large institutional active surveillance cohort of patients diagnosed from 2000 to 2020 (n = 1276), the number of patients meeting NCCN VLR criteria decreased significantly in recent years, with no patient meeting VLR criteria after 2018. By contrast, the multivariable Cancer of the Prostate Risk Assessment (CAPRA) score effectively substratified patients over the same period and was predictive of upgrading on repeat biopsy to Gleason grade group ≥2 on multivariable Cox proportional-hazards regression modeling (hazard ratio 1.21, 95% confidence interval 1.05-1.39; p < 0.01), independent of age, genomic test results, and magnetic resonance imaging findings. These findings suggest that the NCCN VLR criteria are less applicable in the targeted biopsy era, and that the CAPRA score or similar instruments are better contemporary risk stratification tools for men on active surveillance. PATIENT SUMMARY: We investigated whether the National Comprehensive Cancer Network classification of very low risk (VLR) for prostate cancer is relevant in the modern era. We found that in a large group of patients on active surveillance, no man diagnosed after 2018 satisfied the VLR criteria. However, the Cancer of the Prostate Risk Assessment (CAPRA) score discriminated patients by cancer risk at diagnosis and was predictive of outcomes on active surveillance, and thus may be a more relevant classification scheme in the modern era., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Multi-parametric MRI (mpMRI) has proven itself a clinically useful tool to assess prostate cancer (PCa). Our objective was to generate PCa risk maps to quantify the volume and location of both all PCa and high grade (Gleason grade group ≥ 3) PCa. Such capabilities would aid physicians and patients in treatment decisions, targeting biopsy, and planning focal therapy. A cohort of men with biopsy proven prostate cancer and pre-prostatectomy mpMRI were studied. PCa and benign ROIs (1524) were identified on mpMRI and histopathology with histopathology serving as the reference standard. Logistic regression models were created to differentiate PCa from benign tissues. The MRI images were registered to ensure correct overlay. The cancer models were applied to each image voxel within prostates to create probability maps of cancer and of high-grade cancer. Use of an optimum probability threshold quantified PCa volume for all lesions >0.1 cc. Accuracies were calculated using area under the curve (AUC) for the receiver operating characteristic (ROC). The PCa models utilized apparent diffusion coefficient (ADC), T2 weighted (T2W), dynamic contrast-enhanced MRI (DCE MRI) enhancement slope, and DCE MRI washout as the statistically significant MRI scans. Application of the PCa maps method provided total PCa volume and individual lesion volumes. The AUCs derived from lesion analysis were 0.91 for all PCa and 0.73 for high-grade PCa. At the optimum threshold, the PCa maps detected 135 / 150 (90%) histopathological lesions >0.1 cc. This study showed the feasibility of cancer risk maps, created from pre-prostatectomy, mpMR images validated with histopathology, to detect PCa lesions >0.1 cc. The method quantified the volume of cancer within the prostate. Method improvements were identified by determining root causes for over and underestimation of cancer volumes. The maps have the potential for improved non-invasive capability in quantitative detection, localization, volume estimation, and MRI characterization of PCa., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Both the performance characteristics of prostate-specific membrane antigen positron emission tomography and insurance approval improves with increasing prostate-specific antigen (PSA) level causing some physicians to delay post-radical prostatectomy salvage radiation therapy (sRT) after PSA failure. Yet, it is unknown for men with at most one high-risk factor (ie, pT3/4 or prostatectomy [p] Gleason score 8-10) whether a PSA level exists above which initiating sRT is associated with increased all-cause mortality (ACM)-risk and was investigated., Methods: Using a multinational database of 25,551 patients with pT2-4N0 or NXM0 prostate cancer, multivariable Cox regression analysis evaluated whether an association with a significant increase in ACM-risk existed when sRT was delivered above a prespecified PSA level beginning at 0.10 ng/mL and in 0.05 increments up to 0.50 ng/mL versus at or below that level. The model was adjusted for age at and year of radical prostatectomy, established prostate cancer prognostic factors, institution, and the time-dependent use of androgen deprivation therapy., Results: After a median follow-up of 6.00 years, patients who received sRT at a PSA level >0.25 ng/mL had a significantly higher ACM-risk (AHR, 1.49; 95% CI, 1.11 to 2.00; P = .008) compared with men who received sRT when the PSA was ≤0.25 mg/mL. This elevated ACM-risk remained significant for all PSA cutpoints up to 0.50 ng/mL but was not significant at PSA cutpoint values below 0.25 ng/mL., Conclusion: Among patients with at most one high-risk factor, initiating sRT above a PSA level of 0.25 ng/mL was associated with increased ACM-risk.

Objective: Management guidelines encourage self-care in patients with symptomatic osteoarthritis (OA). We undertook this study to investigate the relationship between health literacy (HL) and appropriateness of selection of self-care strategies in people with self-reported symptoms of OA., Methods: We conducted an online national observational, demographically representative, cross-sectional survey of adults (ages 45-74 years). The eligibility criterion of "self-reported OA symptoms" was screened for using guideline-endorsed clinical criteria. Participants completed a custom-built questionnaire that included validated scales for HL, pain intensity, sleep quality, and OA function/disability. Management strategies were grouped into self-care activities, analgesics, and complementary medicines, and analyses of appropriateness were based on predefined, evidence-based quality indicators., Results: Of 6,800 participants, 628 met the inclusion criteria and completed the survey. HL was categorized as follows: low (100 of 628, 15.9%), moderate (317 of 628, 50.5%), and excellent (211 of 628, 33.6%). In the past 7 days, mean pain intensity (0-10 scale) was 3.11 (95% confidence interval [95% CI] 3.06-3.16), and 71.7% of participants (450 of 628) had not achieved adequate pain relief. In the past month, 54.1% (340 of 628) reported disrupted sleep. Participants managed their pain with multiple self-care activities (mean 1.44; 95% CI 1.32-1.57), analgesics (mean 1.74; 95% CI 1.60-1.88), and complementary medicines (mean 1.01; 95% CI 0.90-1.12). There was a statistically significant (P < 0.001) interaction between HL and appropriateness of current management strategies (HL low, guideline-recommended management strategies less likely). Higher HL did not always translate into making appropriate pain management choices., Conclusion: Appropriate selection and use of evidence-based management options is critical for patients with OA to obtain the full benefits from their treatment. Knowledge about suitable choices for OA self-care is suboptimal, and future education should be tailored to different levels of HL., (© 2021 American College of Rheumatology.)

Background: One challenge in transgender research is reliably identifying patients through electronic medical records data, as there is no universal transgender International Classification of Diseases (ICD) code, but rather multiple ICD codes that can be used., Aim: To explore the sensitivity and specificity of 5 commonly used ICD codes to identify transgender patients overall and transgender women specifically (assigned male sex at birth) by using data from the Veterans Affairs (VA), the largest integrated health system in the United States., Methods: Patients aged ≥18 years were identified via ICD-9 codes 302.5 and 302.6 (Ninth Revision) and ICD-10 codes F64.0, F64.8, and F64.9 (Tenth Revision) using VA health records from 2000 to 2021 and stratified by bilateral orchiectomy status., Outcomes: Detailed chart review was performed on 32 randomly selected patients for each code (half with and half without orchiectomy) to confirm transgender status and to perform descriptive analyses., Results: For each ICD code, rates of confirmed transgender status ranged from 88% to 100% for those with and without an orchiectomy, with the majority being transgender women (consistent with most veterans being assigned male sex at birth). Most transgender women (66%-100%) were undergoing estrogen gender-affirming therapy. The majority of provider-driven entries of transgender status took place from 2011 to 2020, with 75% of entries made from 2011 to 2020, consistent with increased recognition and societal acceptance of this population. False negatives were detected at a rate of 15%. Based upon these 5 ICD codes alone, we estimate that the VA has records for 9,449 to 10,738 transgender individuals., Clinical Implications: All 5 codes are very sensitive in identifying transgender patients, and the combination of these codes with orchiectomy is extremely sensitive in identifying transgender women, specifically., Strengths and Limitations: Major strengths of the study are the use of universal ICD codes and a large patient sample size that spans health records nationally and across multiple decades, potentially making our data more generalizable. The main limitation of this study is that subanalyses were performed on a limited number of patients, which prevented us from capturing all false positives and thus from calculating specificity for each code. Similarly, our true negatives were derived from a small, random subset of the population; as such, our calculation for specificity is an estimate., Conclusion: This study highlights a novel method to identify transgender women and paves the way for further research., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Factors that influence prostate cancer treatment decisions are complex, multifaceted, and personal, and may vary by race/ethnicity. Although research has been published to quantify factors involved in decision-making, these studies have been limited to primarily white, and to a lesser extent, Black patients, and quantitative studies are limited for discerning the cultural and contextual processes that shape decision-making., Methods: We conducted 43 semi-structured interviews with a racially and ethnically diverse sample of patients diagnosed with low- and very-low risk prostate cancer who had undergone treatment for their prostate cancer. Interviews were transcribed, independently coded, and analyzed to identify themes salient for decision-making, with attention to sociocultural differences., Results: We found racial and ethnic differences in three areas. First, we found differences in how socialized masculinity influenced patient's feelings about different treatment options. Second, we found that for some men, religion and spirituality alleviated anxiety associated with the active surveillance protocol. Finally, for racially and ethnically minoritized patients, we found descriptions of how historic and social experiences within the healthcare system influenced decision-making., Conclusions: Our study adds to the current literature by expounding on racial and ethnic differences in the multidimensional, nuanced factors related to decision-making. Our findings suggest that factors associated with prostate cancer decision-making can manifest differently across racial and ethnic groups, and provide some guidance for future research., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Nutrition and physical activity are associated with prostate cancer recurrence and mortality. Few randomized controlled trials (RCT) have examined the effects of long-term exercise and diet changes on prostate cancer clinical, biological, and patient-reported outcomes., Methods: Prostate 8-II is a 4-arm RCT among 200 men with prostate cancer who chose radical prostatectomy (RP) as their primary treatment. Men are enrolled prior to RP and randomized to exercise-only, diet-only, exercise + diet, or usual care (50/arm). Participants begin their assigned intervention 0-5 weeks prior to RP and continue for 24-months following surgery. The 3 active intervention arms receive access to a web-portal and text messages, coaching calls, and other intervention resources (e.g., heart rate sensor and resistance bands and/or recipe booklet). Weekly exercise goals for the exercise intervention groups are 150 min moderate or 75 min vigorous aerobic exercise, 2 strength sessions, and 2 flexibility sessions. Diet intervention groups work with a dietitian to customize their goals (e.g., increase cruciferous vegetables, cooked tomatoes, healthy fats, fish; limit processed meats, whole milk). The primary endpoint is biochemical recurrence. Secondary endpoints include change in tumor biomarkers from biopsy to RP as well as patient-reported outcomes (e.g., quality-of-life), blood and urine biomarkers, and anthropometry at 0, 6, 12, and 24 months., Conclusion: This 4-arm RCT will examine the impact of change in exercise and diet (alone or in combination) on prostate cancer recurrence, biology, and quality-of-life., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.A.K is a consultant and board member for Fellow Health Inc., unrelated to the current study. A.L. is the founder of Sportzpeak, Inc., unrelated to the current study., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Clinical guidelines suggest that for low-grade, clinically localized prostate cancer, patients with higher volume of disease at diagnosis may benefit from definitive therapy, although the data remain unclear. Our objective was to determine associations between low-grade prostate cancer volume and outcomes in men managed with primary radical prostatectomy., Materials and Methods: Men with cT1-2N0/xM0/x prostate cancer, prostate specific antigen at diagnosis <10 ng/mL, and Gleason grade group 1 pathology on diagnostic biopsy managed with primary radical prostatectomy were included. Outcomes were pathological upgrade at radical prostatectomy (≥Gleason grade group 2), University of California, San Francisco adverse pathology at radical prostatectomy (≥Gleason grade group 3, pT3/4, or pN1), alternate adverse pathology at radical prostatectomy (≥Gleason grade group 3, ≥pT3b, or pN1), and recurrence (biochemical failure with 2 prostate specific antigen ≥0.2 ng/mL or salvage treatment). Multivariable logistic regression models were used to estimate associations between percentage of positive cores and risk of upgrade and adverse pathology at radical prostatectomy. Multivariable Cox proportional hazards regression models were used to estimate associations between percentage of positive cores and hazard of recurrence after radical prostatectomy., Results: A total of 1,029 men met inclusion criteria. Multivariable logistic regression models demonstrated significant associations between percentage of positive cores and pathological upgrade (OR 1.31, 95% CI 1.1-1.57, P < . 01), but not University of California, San Francisco adverse pathology at radical prostatectomy ( P = . 84); percentage of positive cores was negatively associated with alternate adverse pathology (OR 0.67, 95% CI 0.48-0.93, P = . 02). Multivariable Cox regression models demonstrated no association between percentage of positive cores and hazard of recurrence after radical prostatectomy ( P = . 11)., Conclusions: In men with Gleason grade group 1 prostate cancer, tumor volume may be associated with upgrading at radical prostatectomy, but not more clinically significant outcomes of adverse pathology or recurrence.

Context: Approximately 0.4-1.3% of the worldwide population is transgender. Although the exact prevalence is unknown, there is an increase in open identification as transgender. Among transgender women (TW), the prostate is retained even after gender-affirmation surgery, thus necessitating ongoing screening for prostate cancer (CaP). However, little is known about CaP screening in this population., Objective: To assess our current understanding of CaP incidence and prostate-specific antigen (PSA) screening in TW., Evidence Acquisition: We performed a nonsystematic narrative review of all PubMed publications through June 2022 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Given the limited primary research on this subject, case reports were also included. Studies were reviewed to understand PSA screening practices and reports of CaP in this population, as applicable., Evidence Synthesis: There is no consensus regarding PSA screening in TW from any of the major societies, and TW are largely absent from guidelines. Case report data suggest that TW with CaP may have more aggressive disease, and these cancers may have been pre-existing prior to present before gender-affirming hormone therapy (GAHT) or be castrate-resistant., Conclusions: We are in the infancy of our understanding of PSA screening in TW. Important avenues for future research include understanding the risks/benefits of PSA screening in TW, how best to mitigate potential negative psychological effects of PSA screening in TW, establishing baseline PSA values for those on GAHT (and determining what values should be considered "elevated"), establishing when to initiate PSA screening for those on GAHT, and establishing the accuracy of biomarkers for those undergoing GAHT., Patient Summary: We examined patterns of prostate cancer screening for transgender women. Little is known about prostate cancer incidence or screening in this population. Additional research is needed to establish guidelines for screening in this population., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)