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Importance: Incidence of distant stage prostate cancer is increasing in the United States. Research is needed to understand trends by social and geographic factors., Objective: To examine trends in prostate cancer incidence and mortality rates in California by stage, age, race and ethnicity, and region., Design, Setting, and Participants: This cohort study used mortality data from the California Cancer Registry and California Department of Public Health's Center for Health Statistics, and incidence data from the National Cancer Institute Surveillance, Epidemiology, and End Results program and the US Census. The dataset for these analyses was released in April 2024. Participants included males residing in California between 2004 and 2021. Analyses were conducted from April to October 2024., Exposures: Stage at diagnosis, age, race and ethnicity, and region of California., Main Outcomes and Measures: The delay-adjusted incidence rates and mortality rates were calculated and age-adjusted to the 2000 US standard population. Annual percentage changes (APC) were calculated using NCI's Joinpoint Regression Program., Results: Between 2004 and 2021, there were 387 636 prostate cancer cases (27 938 distant stage) and 58 754 prostate cancer deaths in California. In this study, 203 038 cases (52.4%) occurred among males aged 55 to 69 years, and 153 884 (39.7%) occurred among males 70 years or older. The distribution of race and ethnicity among cases was: 1031 American Indian or Alaska Native (0.3%); 31 366 Asian American, Native Hawaiian, and Pacific Islander (8.1%); 66 695 Hispanic or Latino (17.2%); 36 808 non-Hispanic Black (9.5%); 238 229 non-Hispanic White (61.5%); and 13 507 unknown or other races (3.5%). On average, the incidence of distant prostate cancer increased 6.7% (95% CI, 6.2% to 7.3%) per year between 2011 and 2021. By race and ethnicity, the APC ranged from 6.5% (95% CI, 4.2% to 13.4%) among Asian American, Native Hawaiian, and Pacific Islander males between 2011 and 2021 to 8.0% (95% CI, 6.9% to 9.5%) among Hispanic males between 2014 and 2021. In 9 of the 10 California regions, the incidence of distant prostate cancer increased by approximately 6% or more per year. Prostate cancer mortality rates declined 2.6% per year between 2004 and 2012 but plateaued between 2012 to 2021 (APC, 0.1%; 95% CI, -0.6% to 1.6%). The plateau in mortality occurred across ages, races and ethnicities, and regions., Conclusions and Relevance: In this cohort study among California residents, the incidence of distant stage prostate cancer increased throughout the state between 2011 and 2021. Mortality rates plateaued between 2012 and 2021, ending previous decades of decline. Implementation of more effective prostate cancer screening strategies are critically needed.

Purpose: Serial biopsy is a mainstay for patients on active surveillance (AS) for prostate cancer. multiparametric MRI 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 magnetic resonance (MR)-targeted sampling. The findings for dominant Gleason Grade Group (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.

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.)

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.)

Black men have a greater risk of prostate cancer as well as worse quality of life and more decisional regret after prostate cancer treatment compared to non-Hispanic White men. Furthermore, patients with prostate cancer who primarily obtain information on the internet have significantly more decisional regret compared to other information sources. Our objective was to explore the perspectives of Black patients on the use and impact of the internet for their prostate cancer care. In 2022-2023, we conducted seven virtual focus groups with Black patients with prostate cancer ( n = 22). Transcripts were independently analyzed by two experienced researchers using a constant comparative method. Online sources were commonly used by participants throughout their cancer journey, although informational needs varied over time. Patient factors affected use (e.g., physical health and experience with the internet), and family members played an active role in online information-seeking. The internet was used before and after visits to the doctor. Key topics that participants searched for online included nutrition and lifestyle, treatment options, and prostate cancer in Black men. Men reported many downstream benefits with internet use including feeling more empowered in decision-making, reducing anxiety about treatment and providing greater accountability for research. However, they also reported negative impacts such as feeling overwhelmed or discouraged sorting through the information to identify high-quality content that is personally relevant, as well as increased anxiety or loss of sleep from overuse. In summary, online sources have the potential to positively impact the cancer journey by reinforcing or supplementing information from health care providers, but can be harmful if the information is poor quality, not representative, or the internet is overused., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.)

Purpose: Although the majority of US adults obtain health information on the internet, the quality of information about prostate cancer is highly variable. Black adults are underrepresented in online content about prostate cancer despite a higher incidence of and mortality from the disease. The goal of this study was to explore the perspectives of Black patients with prostate cancer on the importance of racial representation in online content and other factors influencing trust., Materials and Methods: We conducted 7 virtual focus groups with Black patients with prostate cancer in 2022 and 2023. Participants completed an intake questionnaire with demographics followed by a group discussion, including feedback on purposefully selected online content. Transcripts were independently analyzed by 2 investigators experienced in qualitative research using a constant comparative method., Results: Most participants use online sources to look for prostate cancer information. Racial representation is an important factor affecting trust in the content. A lack of Black representation has consequences, including misperceptions about a lower risk of prostate cancer and discouraging further information-seeking. Other key themes affecting trust in online content included the importance of a reputable source of information, professional website structure, and soliciting money., Conclusions: Underrepresentation of Black adults in prostate cancer content has the potential to worsen health disparities. Optimal online communications should include racially diverse representation and evidence-based information in a professional format from reputable sources without financial conflict.

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).)

Introduction: Patients with mental health disorders are at risk for receiving inequitable cancer treatment, likely resulting from various structural, social, and health-related factors. This study aims to assess the relationship between mental health disorders and the use of definitive treatment in a population-based cohort of those with localized, clinically significant prostate cancer., Methods: We conducted a cohort study analysis in SEER (Surveillance, Epidemiology, and End Results)-Medicare (2004-2015). History of a mental health disorder was defined as presence of specific ICD (International Classification of Diseases)-9 or ICD-10 diagnostic codes in the 2 years preceding cancer diagnosis. Descriptive statistics were performed using Wilcoxon rank-sum and χ 2 testing. Multivariable logistic regression was used to evaluate the relationship between mental health disorders and definitive treatment utilization (defined as surgery or radiation)., Results: Of 101,042 individuals with prostate cancer, 7,945 (7.8%) had a diagnosis of a mental health disorder. They were more likely to be unpartnered, have a lower socioeconomic status, and less likely to receive definitive treatment (61.8% vs 68.2%, P < .001). Definitive treatment rates were >66%, 62.8%, 60.3%, 58.2%, 54.3%, and 48.1% for post-traumatic stress disorder, depressive disorder, bipolar disorder, anxiety disorder, substance abuse disorder, and schizophrenia, respectively. After adjusting for age, race and ethnicity, marital status and socioeconomic status, history of a mental health disorder was associated with decreased odds of receiving definitive treatment (OR 0.74, 95% CI 0.66-0.83)., Conclusions: Individuals with mental health disorders and prostate cancer represent a vulnerable population; careful attention to clinical and social needs is required to support appropriate use of beneficial treatments.

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.)

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.)

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).)

Importance: Black men have a higher risk of prostate cancer compared with White men, but Black adults are underrepresented in online content about prostate cancer. Across racial groups, the internet is a popular source of health information; Black adults are more likely to trust online health information, yet have more medical mistrust than White adults., Objective: To evaluate the association between racial representation in online content about prostate cancer and trust in the content and identify factors that influence trust., Design, Setting, and Participants: A randomized clinical trial was conducted from August 18, 2021, to January 7, 2022, consisting of a 1-time online survey. Participants included US men and women aged 40 years and older. Data were analyzed from January 2022 to June 2023., Interventions: Participants were randomized to watch the same video script about either prostate cancer screening or clinical trials presented by 1 of 4 speakers: a Black physician, a Black patient, a White physician, or a White patient, followed by a questionnaire., Main Outcomes and Measures: The primary outcome was a published scale for trust in the information. χ2 tests and multivariable logistic regression were used to compare trust according to the video's speaker and topic., Results: Among 2904 participants, 1801 (62%) were men, and the median (IQR) age was 59 (47-69) years. Among 1703 Black adults, a greater proportion had high trust in videos with Black speakers vs White speakers (72.7% vs 64.3%; adjusted odds ratio [aOR], 1.62; 95% CI, 1.28-2.05; P < .001); less trust with patient vs physician presenter (64.6% vs 72.5%; aOR, 0.63; 95% CI, 0.49-0.80; P < .001) and about clinical trials vs screening (66.3% vs 70.7%; aOR, 0.78; 95% CI, 0.62-0.99; P = .04). Among White adults, a lower proportion had high trust in videos featuring a patient vs physician (72.0% vs 78.6%; aOR, 0.71; 95% CI, 0.54-0.95; P = .02) and clinical trials vs screening (71.4% vs 79.1%; aOR, 0.57; 95% CI, 0.42-0.76; P < .001), but no difference for Black vs White presenters (76.8% vs 73.7%; aOR, 1.11; 95% CI, 0.83-1.48; P = .49)., Conclusions and Relevance: In this randomized clinical trial, prostate cancer information was considered more trustworthy when delivered by a physician, but racial concordance was significantly associated with trust only among Black adults. These results highlight the importance of physician participation and increasing racial diversity in public dissemination of health information and an ongoing need for public education about clinical trials., Trial Registration: ClinicalTrials.gov Identifier: NCT05886751.

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.)

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.

Background: Multiparametric magnetic resonance imaging (MRI) is increasingly utilized to improve the detection of clinically significant prostate cancer. Evidence for serial MRI in men on active surveillance (AS) is lacking., Objective: To evaluate the role of MRI in detecting Gleason grade group (GG) ≥2 disease in confirmatory and subsequent surveillance biopsies for men on AS., Design, Setting, and Participants: This was a single-center study of men with low-risk prostate cancer enrolled in an AS cohort between 2006 and 2018. All men were diagnosed by systematic biopsy and underwent MRI prior to confirmatory ("MRI1") and subsequent surveillance ("MRI2") biopsies. MRI lesions were scored with Prostate Imaging Reporting and Data System (PI-RADS) version 2., Outcome Measurements and Statistical Analysis: The primary outcome was biopsy upgrade to GG ≥ 2 prostate cancer, and the secondary outcome was definitive treatment. Test characteristics for PI-RADS score were calculated. Multivariable logistic and Cox proportional hazard regression models were used to determine the associations between PI-RADS score change and outcomes, on a per-examination basis., Results and Limitations: Of 125 men with a median follow-up of 78 mo, 38% experienced an increase in PI-RADS scores. The sensitivity and positive predictive value of PI-RADS ≥3 for GG ≥ 2 disease improved from MRI1 to MRI2 (from 85% to 91% and from 26% to 49%, respectively). An increase in PI-RADS scores from MRI1 to MRI2 was associated with GG ≥ 2 (odds ratio [OR] 4.8, 95% confidence interval [CI] 1.7-13.2) compared with PI-RADS 1-3 on both MRI scans. Men with PI-RADS 4-5 lesions on both MRI scans had a higher likelihood of GG ≥ 2 than patients with PI-RADS 1-3 lesions on both (OR 3.3, 95% CI 1.3-8.6). Importantly, any increase in PI-RADS scores was independently associated with definitive treatment (hazard ratio 3.9, 95% CI 1.3-11.9). This study was limited by its retrospective, single-center design., Conclusions: The prognostic value of MRI improves with serial examination and provides additional risk stratification. Validation in other cohorts is needed., Patient Summary: We looked at the role of serial prostate magnetic resonance imaging in men with low-risk prostate cancer on active surveillance at the University of California, San Francisco. We found that both consistently visible and increasingly suspicious lesions were associated with biopsy upgrade and definitive treatment., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Importance: Racial disparity in the use of prostate magnetic resonance imaging (MRI) presents obstacles to closing gaps in prostate cancer diagnosis, treatment, and outcome., Objective: To identify clinical, sociodemographic, and structural processes underlying racial disparity in the use of prostate MRI among men with a new diagnosis of prostate cancer., Design, Setting, and Participants: This population-based cohort study used mediation analysis to assess claims in the US Surveillance, Epidemiology, and End Results (SEER)-Medicare database for prostate MRI among 39 534 patients with a diagnosis of localized prostate cancer from January 1, 2011, to December 31, 2015. Statistical analysis was performed from April 1, 2020, to September 1, 2021., Exposure: Diagnosis of prostate cancer., Main Outcomes and Measures: Claims for prostate MRI within 6 months before or after diagnosis of prostate cancer were assessed. Candidate clinical and sociodemographic meditators were identified based on their association with both race and prostate MRI, including the Index of Concentration at the Extremes (ICE), as specified to measure racialized residential segregation. Mediation analysis was performed using nonlinear multiple additive regression trees models to estimate the direct and indirect effects of mediators., Results: A total of 39 534 eligible male patients (3979 Black patients [10.1%] and 32 585 White patients [82.4%]; mean [SD] age, 72.8 [5.3] years) were identified. Black patients with prostate cancer were less likely than White patients to receive a prostate MRI (6.3% vs 9.9%; unadjusted odds ratio, 0.62, 95% CI, 0.54-0.70). Approximately 24% (95% CI, 14%-32%) of the racial disparity in prostate MRI use between Black and White patients was attributable to geographic differences (SEER registry), 19% (95% CI, 11%-28%) was attributable to neighborhood-level socioeconomic status (residence in a high-poverty area), 19% (95% CI, 10%-29%) was attributable to racialized residential segregation (ICE quintile), and 11% (95% CI, 7%-16%) was attributable to a marker of individual-level socioeconomic status (dual eligibility for Medicare and Medicaid). Clinical and pathologic factors were not significant mediators. In this model, the identified mediators accounted for 81% (95% CI, 64%-98%) of the observed racial disparity in prostate MRI use between Black and White patients., Conclusions and Relevance: In this this population-based cohort study of US adults, mediation analysis revealed that sociodemographic factors and manifestations of structural racism, including poverty and residential segregation, explained most of the racial disparity in the use of prostate MRI among older Black and White men with prostate cancer. These findings can be applied to develop targeted strategies to improve cancer care equity.

Purpose: For men with clinically localized prostate cancer outcomes of continuing active surveillance (AS) after biopsy progression are not well understood. We aim to determine the impact of continuing AS and delayed definitive treatment after biopsy progression on oncologic outcomes., Materials and Methods: Participants in our prospective AS cohort (1990-2018) diagnosed with grade group (GG) 1, localized prostate cancer, with prostate specific antigen <20 who were subsequently upgraded to ≥GG2, and underwent further surveillance (biopsy/imaging/prostate specific antigen) were identified. Patients were stratified by post-progression followup into 3 groups: continue AS untreated, pursue early radical prostatectomy (RP) ≤6 months, or undergo late RP within 6 months to 5 years of progression. Patients receiving other treatments were excluded. We compared characteristics between groups and examined the associations of early vs late RP with risk of adverse pathology (AP) at RP and recurrence-free survival (RFS) after RP., Results: Of 531 patients with biopsy progression and further surveillance 214 (40%) remained untreated, 192 (36%) pursued early RP and 125 (24%) underwent late RP. Among patients who underwent early vs late RP, there was no difference in GG (p=0.15) or AP (55% vs 53%, p=0.74) rate at RP, or 3-year RFS (80% vs 87%, log-rank p=0.64) after RP. In multivariable models, only Cancer of Prostate Risk Assessment post-surgical score was associated with risk of RFS (HR=1.42 per point, 95% CI 1.24-1.64)., Conclusions: Among patients continuing AS after biopsy progression, 60% underwent surgery within 5 years. Delayed surgery after progression was not associated with higher risk of AP or RFS. This suggests select patients may be able to safely delay treatment after progression.

Purpose: The association between androgen deprivation therapy (ADT) and dementia in men with prostate cancer remains inconclusive. We assessed the association between cumulative ADT exposure and the onset of dementia in a nationwide longitudinal registry of men with prostate cancer., Materials and Methods: A retrospective analysis of men aged ≥50 years from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry was performed. The primary outcome was onset of dementia after primary treatment. ADT exposure was expressed as a time-varying independent variable of total ADT exposure. The probability of receiving ADT was estimated using a propensity score. Cox proportional hazards regression was performed to determine the association between ADT exposure and dementia with competing risk of death, adjusted for propensity score and clinical covariates among men receiving various treatments., Results: Of 13,570 men 317 (2.3%) were diagnosed with dementia after a median of 7.0 years (IQR 3.0-12.0) of followup. Cumulative ADT use was significantly associated with dementia (HR 2.02; 95% CI 1.40-2.91; p <0.01) after adjustment. In a subset of 8,506 men, where propensity score matched by whether or not they received ADT, there was also an association between ADT use and dementia (HR 1.59; 95% CI 1.03-2.44; p=0.04). There was no association between primary treatment type and onset of dementia in the 8,489 men in the cohort who did not receive ADT., Conclusions: Cumulative ADT exposure was associated with dementia. This increased risk should be accompanied by a careful discussion of the needs and benefits of ADT in those being considered for treatment.

Background: Active surveillance (AS) is generally recognized as the preferred option for men with low-risk prostate cancer. Current guidelines use prostate-specific antigen (PSA) of 10-20 ng/mL or low-volume biopsy Gleason grade group (GG) 2 as features that, in part, define the favorable intermediate-risk disease and suggest that AS may be considered for some men in this risk category., Methods: We identified 26,548 men initially managed with AS aged <80 years, with clinically localized prostate cancer (cT1-2cN0M0), PSA ≤ 20 ng/mL, biopsy GG ≤ 2 with percent positive cores ≤33% and who converted to treatment with radical prostatectomy from the surveillance, epidemiology, and end results prostate with the watchful waiting database. Multivariable logistic regression was performed to determine predictors of adverse pathology at RP according to PSA level (<10 vs 10-20 ng/mL) and GG (1 vs 2)., Results: Of 1731 men with GG 1 disease and PSA 10-20 ng/mL, 382 (22.1%) harbored adverse pathology compared to 2340 (28%) of 8,367 men with GG 2 and a PSA < 10 ng/mL who had adverse pathology at RP. On multivariable analysis, the odds of harboring adverse pathology with a PSA 10-20 ng/mL (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.71-2.05, p < 0.001) was less than that of GG 2 (OR 2.56, 95%CI 2.40-2.73, p < 0.001) after adjustment., Conclusions: Our results support extending AS criteria more permissively to carefully selected men with PSA 10-20 ng/mL and GG 1 disease., (© 2021. The Author(s).)

Background: Urinary incontinence after radical prostatectomy affects many men. In addition to surgical and patient factors, longer preoperative membranous urethral length (MUL) has been suggested to be associated with improved postoperative urinary continence outcomes. Here, we assess the association of preoperative MUL and the risk of persistent postoperative urinary incontinence after robot-assisted radical prostatectomy (RARP) for prostate cancer on extended follow-up., Methods: All participants underwent RARP at the University of California, San Francisco between 2000-2018. Patients were excluded if preoperative MRI-measured MUL was not performed by a radiologist. A single, blinded urologist remeasured MUL retrospectively. Logistic regression models examined associations between radiologist- and urologist-measured MUL and likelihood of persistent incontinence post-RARP by two definitions: strict incontinence (>0 pad/day) and social incontinence (>1 pad/day)., Results: In 251 men with a median follow-up of 42 months (IQR 29-76), the median MUL measurements were 14 mm ([IQR 12-17], radiologist) and 15 mm ([IQR 12-18], urologist) with poor agreement (interclass correlation coefficient 0.34). On logistic regression, urologist-measured longer MUL was associated with lower likelihood of strict incontinence within 6 months (odds ratio [OR] 0.87; 95% confidence interval [CI] 0.81-0.94) and 12 months (OR 0.90; 95% CI 0.82-0.98) and social incontinence within 6 months (OR 0.93; 95% CI 0.86-1.00) and 12 months (OR 0.84; 95% CI 0.74-0.95). Radiologist-measured longer MUL was associated with lower likelihood of strict incontinence within 6 months (OR 0.93; 95% CI 0.87-1.00) and social within 12 months (OR 0.87; 95% CI 0.77-1.00). MUL was not associated with likelihood of strict or social incontinence within 24 months., Conclusion: Preoperative MRI-measured MUL was not associated with urinary incontinence after 12 months post-RARP. Poor agreement between radiologists' and urologist's measurements supports standardizing MUL measurements to establish the likelihood of early incontinence., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Active surveillance (AS) is a safe and accepted option for managing men with low-risk prostate cancer. Nevertheless, some patients lack confidence in or access to AS. Focal therapy (FT) is a possible alternative to radical treatment for such patients., Objective: We evaluated dominant tumor (DT) progression across serial biopsies to determine whether men on AS could be reasonable candidates for FT., Design, Setting, and Participants: Men enrolled in AS at University of California, San Francisco between 1996 and 2017 with low/intermediate risk were included., Outcome Measurements and Statistical Analysis: Changes in biopsy grade, volume, and focality of the DT over time were assessed. Focality (good or poor for FT) was defined by the number of cores, laterality, and contiguity of prostate sites containing tumor (based on pathology reports). Candidates (either for targeted/quadrant ablation or for hemigland ablation) were defined based on good focality, grade group (GG) ≤2, and low-volume disease. Patients were classified as favorable (GG ≤ 2 with good focality and concordant multiparametric magnetic resonance imaging [mpMRI]) or unfavorable (poor focality or high-volume disease or discordant mpMRI) for FT at surveillance biopsies., Results and Limitations: A total of 1057 men met the inclusion criteria. The median number of biopsies per patient was three (interquartile range 2-4), and 196 patients (18.5%) underwent five or more biopsies. At confirmatory biopsy, 43% remained candidates for FT (67% for targeted/quadrant ablation and 33% for hemigland ablation) and 20% had a negative biopsy. Of the candidates for FT at initial biopsy, 11% had less favorable characteristics at confirmatory biopsy. Among candidates for FT based on both initial and confirmatory biopsies, 70% remained favorable for hemigland ablation at subsequent biopsies. Limitations include retrospective design and mpMRI information only at surveillance biopsy., Conclusions: Serial biopsy findings in men with early-stage cancer on AS show that tumor location remains relatively stable and significant changes in grade and/or volume occur largely in the DT. Combined diagnostic and confirmatory biopsy findings help better select patients for FT than the use of the diagnostic biopsy alone., Patient Summary: In a large cohort of patients on active surveillance for prostate cancer, we evaluated changes across serial biopsies to identify potential candidates for focal therapy (FT). Our findings showed that the dominant tumor remained stable over time and the majority of men were favorable candidates for FT., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Lesion-targeted prostate biopsy based on multiparametric magnetic resonance imaging (mpMRI) has been shown to be superior to systematic transrectal ultrasound (TRUS) biopsy (SBx) alone in men at risk for prostate cancer (PCa). However, the incremental benefit of MRI-targeted biopsy (MBx) beyond SBx with ultrasound-targeted biopsy (UBx) is less clear., Objective: We performed a three-way comparison of UBx versus MBx versus SBx for PCa detection., Design, Setting, and Participants: A prospective, single-center cohort study was conducted on consecutive patients with PCa suspicion or low-risk PCa on active surveillance (AS). All men had at least one lesion (Prostate Imaging Reporting and Data System [PI-RADS] ≥3) on pre-biopsy mpMRI. UBx, MBx, and SBx were performed during the same encounter, and the urologists were blinded to MRI results and targeting until both SBx and UBx were completed., Outcome Measurements and Statistical Analysis: The ability of each biopsy type to identify the highest grade group (GG) was determined, and UBx and MBx were compared using a paired t test., Results and Limitations: We prospectively enrolled 201 consecutive men undergoing targeted prostate biopsy: 72 (36%) were biopsy-naïve, 34 (17%) had a prior negative SBx, and 95 (47%) were on AS. Median age and prostate-specific antigen were 66 yr (interquartile range [IQR] 62-71) and 6.8 ng/ml (IQR 4.9-9.8), respectively. Suspicious hypoechoic lesions were reported on TRUS in 69%. Among the 169 men with PCa, SBx detected the highest GG or was equivalent to UBx/MBx in 136 (80%) men. UBx detected the highest GG or was equivalent to MBx in 19 (11%) men, and MBx alone detected the highest GG in 14 (8%) men. There was no significant difference between UBx and MBx in direct comparison (p = 0.08). Limitations include that patients were not randomized, our population was heterogeneous, and TRUS expertise at a tertiary care academic center might not reflect routine practice., Conclusions: In the setting of high expertise and experience with both ultrasound and MRI, MBx offers only a modest benefit over SBx and UBx., Patient Summary: At a highly experienced academic medical center, we examined the detection rates of prostate cancer among men undergoing prostate biopsy using three techniques: transrectal ultrasound lesion-targeted biopsy, magnetic resonance imaging-targeted biopsy, and systematic biopsy. We identified a few more cases of aggressive prostate cancer with magnetic resonance imaging-targeted biopsy, but a large majority was found by ultrasound alone., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: To determine if benign glandular tissue at the surgical margin (BGM) is associated with detectable prostate specific antigen (PSA) and/or biochemical recurrence (BCR) after radical prostatectomy (RP)., Materials and Methods: Participants underwent RP for localized prostate cancer between 2004 and 2018. Regression analysis was used to identify demographic, clinical and surgical factors associated with the likelihood of BGM presence on surgical pathology. Oncologic outcomes included detectable PSA (>0.03 ng/ml), BCR (≥0.2 ng/ml) and progression to BCR or salvage treatment after detectable PSA. Life tables and Cox proportional hazards regression models were used to determine the association of BGM and risk of oncologic outcomes., Results: A total of 1,082 men underwent RP for localized prostate cancer with BGM reported on surgical pathology and an undetectable postoperative PSA. BGM was present on 249 (23%) specimens. Younger age, bilateral nerve sparing surgery and robotic approach were associated with presence of BGM while malignancy at the surgical margin (MSM) was not. At 7 years after RP, 29% experienced detectable PSA and 11% had BCR. In the subgroup of men who reached detectable PSA, 79% had progression within 7 years. On multivariate Cox proportional hazards regression, BGM status was not independently associated with detectable PSA, BCR and/or progression from detectable PSA to BCR or salvage treatment., Conclusions: The presence of BGM at RP was not associated with increased risk of MSM, detectable PSA, BCR or progression after detectable PSA.

Background: A detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) is an unfavorable prognostic factor. However, not all men with a detectable PSA experience recurrence. We describe the natural history and outcomes in men with a detectable PSA following RP in a contemporary cohort., Methods: A retrospective analysis of men who underwent RP for non-metastatic prostate cancer at the University of California, San Francisco from 2000 to 2020 was performed. A detectable PSA was defined as PSA ≥ 0.03 ng/ml within 6 months of RP. Cox regression models tested the effect of detectable PSA on the development of metastasis, prostate cancer-specific mortality, and overall survival., Results: We identified 2941 men who had RP with 408 (13.9%) with a detectable PSA within the first 6 months. The median follow-up was 4.42 years (interquartile range [IQR], 2.58-8.00). In total, 296 (72.5%) men with a detectable PSA had salvage treatment at a median of 6 months (IQR, 4-11). One hundred sixteen of these men had PSA failure after salvage treatment at a median of 2.0 years (IQR, 0.7-3.8). On multivariable Cox regression, the risk of development of metastasis (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.09; p = .01), prostate cancer-specific mortality (HR, 1.13; 95% CI, 1.05-1.21; p = .0005), and overall mortality (HR, 1.07; 95% CI, 1.03-1.12; p = .002) was associated with PSA velocity after salvage treatment in men with a detectable PSA., Conclusions: Men with a detectable PSA after RP may have excellent long-term outcomes. PSA velocity after salvage treatment may be an important predictor for the development of metastasis, prostate cancer-specific mortality, and overall mortality., (© 2021 Wiley Periodicals LLC.)

Purpose of Review: This study aimed to summarize evidence published between 1999 and June 2020 examining diet and lifestyle after prostate cancer (PC) diagnosis in relation to risk of biochemical recurrence, PC progression, and PC-specific mortality., Recent Findings: Secondary prevention is an important research area in cancer survivorship. A growing number of studies have reported associations between post-diagnostic modifiable behaviors and risk of PC outcomes. Evidence on modifiable lifestyle factors and PC remains limited. Where multiple studies exist, findings are often mixed. However, studies consistently suggest that smoking and consumption of whole milk/high-fat dairy are associated with higher risk of PC recurrence and mortality. In addition, physical activity and ½ to 1 glass of red wine/day have been associated with lower risk of recurrence and PC-specific mortality. Greater inclusion of racially/ethnically diverse groups in future research is necessary to understand these relationships in populations most impacted by adverse PC outcomes.

Background: The benefit of pelvic lymph node dissection (PLND) at radical prostatectomy (RP) remains unclear given the low prevalence of known nodal disease (pN1) and concerns about its therapeutic utility., Objective: To characterize the impact of PLND and secondary treatment on oncologic outcomes., Design, Setting, and Participants: Cohort study of men who underwent primary RP with PLND for prostate cancer (PCa) at our institution since 2003. Men stratified by nodal status., Outcome Measures and Statistical Analysis: Outcomes include biochemical recurrence-free survival (bRFS), overall survival, and PCa-specific mortality (PCSM). Multivariable Cox regression models used for each outcome., Results and Limitations: Of 1,543 men who underwent primary RP, 174 (11%) had pN1 disease. Median follow-up was 34 months (interquartile range, 15-62). Seven-year outcomes were similar whether less than or ≥14 LNs dissected. Among node-positive patients, 29% had undetectable (UDT) prostate-specific antigen (PSA), 11% had UDT PSA + adjuvant therapy, and 60% had detectable PSA, and 7-year bRFS differed (75% for UDT PSA, 90% for UDT + adjuvant therapy, 38% for detectable PSA, p < .01). Survival outcomes did not differ. In multivariable analysis, detectable PSA (vs. UDT, HR 5.2, 95% CI 2.0-13.3) associated with worse bRFS. After salvage treatment, 7-year outcomes did not differ between groups. Study limited by retrospective review., (© 2020 Wiley Periodicals LLC.)

Purpose: Men with low risk prostate cancer on active surveillance undergo multiple biopsies over time. The long-term clinical significance of consecutively negative biopsies is not known., Materials and Methods: Men with low risk prostate cancer prospectively enrolled in an active surveillance database with at least 4 biopsies were included in the study. Exposure variables were 0, 1 or 2 consecutively negative biopsies after diagnosis. Other variables included age, prostate specific antigen, prostate specific antigen density, Gleason grade group, percent positive cores and magnetic resonance imaging findings. Outcome variables were the detection of any cancer at fourth biopsy and active treatment., Results: A total of 514 men were included, with 112 (22%) men having 1 negative biopsy and 78 (15%) with 2 consecutively negative biopsies. Median prostate specific antigen density was lower for men with 1 negative biopsy (0.11) and consecutively negative biopsies (0.10) compared to men who never had a negative biopsy (0.13, p <0.01). On univariable logistic regression higher prostate specific antigen density (OR 1.68, 95% CI 1.16-2.45) and suspicious magnetic resonance imaging lesions (OR 2.00, 95% CI 1.16-3.42) were associated with a higher likelihood of detecting cancer on fourth biopsy. On multivariable logistic regression 1 negative biopsy (OR 0.22, 95% CI 0.12-0.41) and consecutively negative biopsies (OR 0.12, 95% CI 0.06-0.24) were associated with a lower likelihood of detecting cancer at outcome biopsy. Unadjusted 10-year treatment-free survival was highest for patients with consecutively negative biopsies (84%) and 1 negative biopsy (74%) than those who had none (66%) (log rank p=0.02)., Conclusions: Consecutively negative surveillance biopsies are correlated with favorable clinical risk factors and independently associated with subsequent negative biopsy and lower risk of active treatment.

Purpose: Few validated clinical tools currently exist to standardize the frequency of biopsies for men on active surveillance for low risk prostate cancer. We determined predictors of biopsy reclassification at specific time points after enrollment on active surveillance., Materials and Methods: We identified men with clinically low risk prostate cancer prospectively enrolled on active surveillance at the University of California, San Francisco between 2000 and 2016. Biopsy reclassification was defined as Gleason Grade Group 2 or greater on subsequent biopsy. Multivariable Cox proportional hazards regression models were used to identify factors associated with risk of biopsy reclassification at first surveillance biopsy and 1 to 3, 3 to 5 and 5 to 10 years after enrollment, adjusting for clinicodemographic factors, PI-RADS® (Prostate Imaging Reporting and Data System) score and genomic testing., Results: A total of 1,031 men were included in the study. On multivariable analysis biopsy reclassification was associated with prostate specific antigen density 0.15 or greater (HR 3.37, 95% CI 1.83-6.21), percentage biopsy cores positive (HR 1.27, 95% CI 1.05-1.54) and high genomic score (HR 2.81, 95% CI 1.21-6.52) at first surveillance biopsy and also at 1 to 3 years, after adjustment. Prostate specific antigen density 0.15 or greater (HR 2.36, 95% CI 1.56-3.56) and prostate specific antigen kinetics (HR 2.19, 95% CI 1.43-3.34) were associated with reclassification at 3 to 5 years. A PI-RADS 4-5 score was not associated with biopsy reclassification at any time point., Conclusions: High genomic score, prostate specific antigen kinetics and prostate specific antigen density 0.15 or greater were associated with reclassification within 3 years of commencing active surveillance, and prostate specific antigen kinetics and prostate specific antigen density 0.15 or greater remained associated with reclassification at 5 years after diagnosis.

Importance: Active surveillance (AS) is now recognized as the preferred management option for most low-risk prostate cancers to minimize risks of overtreatment. Despite increasing use of AS in the US, wide regional variability has been observed, and these regional variations in contemporary practice have not been well described., Objective: To explore variations between county and Surveillance, Epidemiology, and End Results (SEER) regions in AS in the US., Design, Setting, and Participants: A cohort study using the SEER Prostate with Watchful Waiting (WW) database linked to the County Area Health Resource File for detailed county-level demographics and physician distribution data was conducted from January 2010 to December 2015. Analysis was performed in October 2020. A total of 79 825 men with clinically localized, low-risk prostate cancer eligible for AS or WW were included., Exposures: Multiple patient-, county-, and SEER region-level factors, including age, year of diagnosis, county-level densities of urologists, radiation oncologists, primary care physicians, and SEER registry region., Main Outcomes and Measures: Use of AS or WW as the initial reported treatment strategy were noted. Hierarchical mixed-effect logistic regression models were used to evaluate clustered random regional variation on use of AS or WW. Temporal trends by year in proportions of initial treatment type, as well as county-level local variation, were also estimated., Results: Of 79 825 men (mean [SD] age, 62.8 [7.6] years, 11 292 [14.1%] non-Hispanic Black, 7506 [9.4%] Hispanic) with low-risk prostate cancer, the mean annualized percent increase in AS rates from 2010 to 2015 ranged from 6.3% in New Mexico to 81.0% in New Jersey. Differences across SEER regions accounted for 17% of the total variation in AS. Increasing age (51-60 years: odds ratio [OR], 1.33; 95% CI, 1.21-1.46; 61-70 years: OR, 1.86; 95% CI, 1.70-2.04; 71-80 years: OR, 2.26; 95% CI, 2.05-2.50) was associated with greater odds of AS. Hispanic ethnicity (OR, 0.79; 95% CI, 0.74-0.85), T category (OR, 0.79; 95% CI, 0.73-0.84), and Medicaid enrollment (OR, 0.73; 95% CI, 0.66-0.81) were associated with lower odds of AS. Black race, county-level socioeconomic factors (household income, educational level, and city type), and specialist densities were not associated with AS use., Conclusions and Relevance: In this US cohort study based on the SEER-WW database, although the use of AS increased, considerable practice variation appeared to be associated with geographic location, but use of AS was not associated with Black race, specialty professional density, or socioeconomic factors. This small area variation underlies the broader national trends in AS practice and may inform policies aimed at continuing to affect risk-appropriate care for men throughout the US.

Purpose: We assessd the long-term outcomes from a large prospective cohort of men diagnosed with prostate cancer managed with active surveillance and determined the clinical prognostic factors that may predict the risk of metastases., Materials and Methods: We retrospectively reviewed data of men enrolled on active surveillance at our institution between 1990 and 2018 with low or intermediate risk disease (stage cT1-2, prostate specific antigen less than 20 ng/ml, and biopsy Grade Group [GG]1-2). Patients were classified into 3 groups by diagnostic GG and prostate specific antigen density. Primary outcome was metastatic prostate cancer detected on imaging or at prostatectomy. In addition, upgrade at surveillance biopsy, active treatment, and overall and prostate cancer specific survival outcomes were assessed. Cox proportional hazards regression models were used., Results: A total of 1,450 men met the inclusion criteria. Median followup was 77 months (IQR 49-114). The 7-year metastasis-free survival rate was 99%. Metastases developed in 15 men at a median of 62 months (IQR 29-104), of which 69% were confined to lymph nodes. Men with GG2 had a lower metastasis-free survival rate compared to those with GG1 disease. GG2, prostate specific antigen velocity and PI-RADS® 4-5 lesions on multiparametric magnetic resonance imaging were associated with a higher risk of metastases. The 7-year prostate cancer specific survival was greater than 99%., Conclusions: Active surveillance seems to preserve favorable long-term prognosis, as metastases and prostate cancer specific death are rare. However, the higher risk of metastases associated with higher Gleason grade, prostate specific antigen velocity, and characteristics on multiparametric magnetic resonance imaging should be considered when selecting and counseling patients for active surveillance.

Background: Active surveillance (AS)/watchful waiting (WW) strategy for localized prostate cancer (PCa) is increasingly and broadly endorsed as a preferred option for initial treatment of men with very low- and low-risk PCa, but outcomes can be difficult to analyze in traditional, population-based registries. The recently released Surveillance, Epidemiology, and End Results (SEER) Prostate with WW dataset provides an opportunity to understand national patterns and trends in AS/WW, but the data source itself has not been well described., Objective: To provide a comprehensive description of this dataset and investigate possible biases due to missing data., Design, Setting, and Participants: The SEER is a population-based epidemiologic registry in the USA. Newly diagnosed PCa patient data were collected from 18 SEER registries between 2010 and 2015, with inclusion of a new treatment variable for AS/WW. We identified 316 724 patients in the entire cohort and 257 060 men with clinically localized PCa (T1-2N0M0)., Intervention: Various primary treatments for PCa., Outcome Measurements and Statistical Analysis: The degree of missing data for each variable was measured. In order to investigate possible bias due to missing data for cancer characterization, we compared two versions of the data: one that excluded cases with missing data and one dataset generated applying multiple imputations., Results and Limitations: Only 46% of cases had complete data on basic cancer characteristics for risk stratification. The excluded dataset (N=118 821) differed significantly from the multiple imputation dataset (N=257 060) in the distribution of every reported variable (all p<0.001). The dataset does not distinguish WW from AS, which is a limitation., Conclusions: While the SEER Prostate with WW dataset offers a new method to describe treatment trends for men with PCa, including the use of AS/WW, the amount of missing data should not be ignored., Patient Summary: While the Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting dataset offers a new method to describe treatment trends for men with prostate cancer, including the use of active surveillance, it has a significant amount of missing data, which can be a source of potential bias if not addressed properly., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

OBJECTIVE. Elevated prostate-specific antigen density (PSAD) based on transrectal ultrasound (TRUS) measurements has been shown to be strongly associated with clinically significant disease and to predict progression on active surveillance (AS) for men with disease that is at a low stage or grade. We hypothesized that elevated MRI PSAD is similarly associated with increased risk of progression on subsequent biopsy. MATERIALS AND METHODS. In this retrospective study, men with Gleason score of 3+3 on diagnostic TRUS-guided biopsy who were managed with AS, had undergone MRI, and had at least one additional biopsy were included. MRI PSAD was calculated using prostate volume on MRI and prostate-specific antigen level temporally closest to the MRI. Multivariable logistics regression models were used to evaluate the association between MRI PSAD and predictors of upgrade on serial biopsy. RESULTS. A total of 166 patients were identified, of whom 74 (44.6%) were upgraded to a Gleason score of 7 or higher on subsequent biopsy. Lesions with Prostate Imaging Reporting and Data System (PI-RADS) scores of 4 and 5 more commonly had MRI PSAD of 0.15 ng/mL 2 or higher (51.93% vs 22.22%, p = 0.01) than lesions with PI-RADS scores of 1-3. Median MRI PSAD was significantly higher in the upgraded group compared with the group that was not upgraded (0.15 ng/mL 2 vs 0.11 ng/mL 2 , p = 0.01). MRI PSAD was significantly associated with increased odds of upgrading on subsequent biopsy (log transformation; odds ratio, 1.9 [95% CI, 1.2-2.8]; p = 0.01) after adjusting for age and length of follow-up. CONCLUSION. MRI PSAD was significantly associated with Gleason score upgrading on subsequent biopsy for men initially diagnosed with Gleason 3+3 disease. Although this result is intuitive, to our knowledge it has not been previously shown. As MRI utilization increases, MRI PSAD can aid in risk stratification for men managed with AS.

Purpose of Review: Active surveillance is becoming more widely accepted as an initial management option for carefully selected men with favorable intermediate-risk prostate cancer (PCa). As prospective active surveillance cohorts mature sufficiently to begin evaluating longer-term outcomes, consensus on more precise evidence-based guidelines is needed to identify the patient cohorts who may be safely managed with active surveillance and what the ideal surveillance protocol entails., Recent Findings: Long-term outcomes updates have suggested a trend toward worse 15-year survival outcomes for intermediate-risk patients on active surveillance compared with definitive treatment, but 'intermediate-risk' is a broad category and there is a subset of favorable intermediate-risk patients for whom survival outcomes remain equivalent. Promising updates to current risk stratification include consideration of genomic classifiers, advanced imaging and more nuanced interpretation of biopsy results., Summary: Despite widespread acknowledgement of the pitfalls of overtreatment in clinically localized PCa, utilization of active surveillance in the intermediate-risk population remains marginal, in part due to the absence of easily interpretable consensus recommendations. As more long-term outcomes data become available for this subgroup, the field is now poised to refine the definition of favorable intermediate-risk patients for whom active surveillance is a safe, evidence-based first-line management option.

Purpose: Genomic testing may improve risk stratification in men with prostate cancer managed by active surveillance. We aimed to characterize the stability and usefulness of serial genomic test scores in men undergoing serial biopsies during active surveillance., Materials and Methods: We compiled clinical and disease characteristics of men on active surveillance using an institutional Urologic Outcomes Database. We included patients initially diagnosed with Gleason 3 + 3 prostate cancer who elected active surveillance and received 2, 17-gene GPS (Genomic Prostate Score) results. We examined the association of GPS results and Gleason grade reclassification (Gleason 3 + 4 or greater) with definitive treatment using multivariable Cox proportional hazards regression models., Results: We identified 111 men who underwent serial genomic testing. There were 49 grade reclassification events (44%) at a median followup of 64 months. The mean ± SD GPS change between the first and second biopsies was 2.1 ± 10.3. The GPS at first biopsy (per 5 units HR 1.04, 95% CI 1.00-1.07, p=0.03) was associated with an upgrade at second biopsy, although the second GPS was not (HR 1.02, 95% CI 0.99-1.05, p=0.13). The first and second GPSs (HR 1.09, 95% CI 1.04-1.14 and HR 1.09, 95% CI 1.04-1.14, each p <0.01) were associated with active treatment., Conclusions: The GPS undergoes small changes with time. Absolute GPS results at the first and second biopsies were associated with Gleason upgrading and transition from active surveillance to active treatment.

Purpose: Cancer pathology findings are critical for many aspects of care but are often locked away as unstructured free text. Our objective was to develop a natural language processing (NLP) system to extract prostate pathology details from postoperative pathology reports and a parallel structured data entry process for use by urologists during routine documentation care and compare accuracy when compared with manual abstraction and concordance between NLP and clinician-entered approaches., Materials and Methods: From February 2016, clinicians used note templates with custom structured data elements (SDEs) during routine clinical care for men with prostate cancer. We also developed an NLP algorithm to parse radical prostatectomy pathology reports and extract structured data. We compared accuracy of clinician-entered SDEs and NLP-parsed data to manual abstraction as a gold standard and compared concordance (Cohen's κ) between approaches assuming no gold standard., Results: There were 523 patients with NLP-extracted data, 319 with SDE data, and 555 with manually abstracted data. For Gleason scores, NLP and clinician SDE accuracy was 95.6% and 95.8%, respectively, compared with manual abstraction, with concordance of 0.93 (95% CI, 0.89 to 0.98). For margin status, extracapsular extension, and seminal vesicle invasion, stage, and lymph node status, NLP accuracy was 94.8% to 100%, SDE accuracy was 87.7% to 100%, and concordance between NLP and SDE ranged from 0.92 to 1.0., Conclusion: We show that a real-world deployment of an NLP algorithm to extract pathology data and structured data entry by clinicians during routine clinical care in a busy clinical practice can generate accurate data when compared with manual abstraction for some, but not all, components of a prostate pathology report.

Prostate cancer remains a leading cause of cancer-related death in men. Concurrently, the incidence of metastatic hormone-sensitive prostate cancer (mHSPC) at diagnosis has significantly risen as a result, in part, of recent advances in imaging. Given the increased utilization of prostate-specific membrane antigen-targeted positron emission tomography imaging and other modalities with improved accuracy in the detection of cancer, combined with changes in screening and other secular trends, more men get diagnosed at an oligometastatic stage in which timely treatment may improve survival. However, the optimal timing of initiation and the specific sequence of systemic agents are not yet clearly defined. Worldwide, both urologists and oncologists may primarily direct the medical management of mHSPC. This collaboration potentially invites differing treatment recommendations dependent upon the treating physician's medical specialty. Ideally, a shared decision-making approach incorporating multidisciplinary tumor board discussions and personalized analysis will provide personalized treatment recommendations to optimize the benefit for mHSPC patients. Here, we conducted a concise review and evaluation of existing literature, and provide one perspective on health care delivery for mHSPC worldwide. PATIENT SUMMARY: Given the improvement in imaging techniques and changes in screening practices, the incidence of metastatic hormone-sensitive prostate cancer will likely continue to rise. An early, multimodal treatment approach involving a multidisciplinary team is critical to delivering the best care to this patient population., (Copyright © 2018. Published by Elsevier B.V.)

Management of prostate cancer presents unique challenges because of the disease's variable natural history. Accurate risk stratification at the time of diagnosis in clinically localized disease is crucial in providing optimal counseling about management options. To accurately distinguish pathologically indolent tumors from aggressive disease, risk groups are no longer sufficient. Rather, multivariable prognostic models reflecting the complete information known at time of diagnosis offer improved accuracy and interpretability. After diagnosis, further testing with genomic assays or other biomarkers improves risk classification. These postdiagnostic risk assessment tools should not supplant shared decision making, but rather facilitate risk classification and enable more individualized care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose of Review: Active surveillance has become the recommended management strategy for most patients with low-risk prostate cancer (PCa), but whether surveillance criteria can be expanded without compromising oncologic outcomes is a matter of debate. Whereas there is essentially uniform consensus that those with low-risk disease can be safely managed with AS, those with intermediate-risk disease, younger men and African-American men are often excluded., Recent Findings: Outcome data for intermediate-risk patients managed by active surveillance demonstrate acceptable oncologic outcomes, but there is also evidence that such patients have higher rates of progression, adverse disease and metastatic disease. Studies evaluating the utility of quantitative Gleason grade, the use of biomarkers and multiparametric MRI are emerging and are likely to refine risk assessment. Literature describing the effects of young age on outcomes is lacking, but early data appear promising. Data on African-American men show varied results that are sometimes contradictory and further investigation is needed to elucidate the impact of race, independent of socioeconomic status., Summary: Patients with intermediate-risk PCa should not be excluded from active surveillance based on any single, borderline criterion; rather, treatment decisions should be based on the full clinical picture, and may be further refined by patient characteristics and adjunctive tools.

Purpose of Review: In 2012, the United States Preventive Services Task Force (USPSTF) issued a grade 'D' recommendation against the use of routine prostate-specific antigen (PSA)-based screening for any men. This recommendation reflects critical misinterpretations of the available evidence base regarding benefits and harms of PSA screening and has influenced the nationwide landscape of prostate cancer screening, diagnosis, and treatment., Recent Findings: Following the USPSTF recommendation, a substantial decline in PSA screening was noted for all age groups. Similarly, overall rates of prostate biopsy and prostate cancer incidence have significantly decreased with a shift toward higher grade and stage disease upon diagnosis. Concurrently, the incidence of metastatic prostate cancer has significantly risen in the United States. These trends are concerning particularly for the younger men with occult high-grade disease who are expected to benefit the most from early detection and definitive prostate cancer treatment., Summary: These emerging trends in PSA screening and prostate cancer incidence following the USPSTF recommendation may have significant public health implications. Due to the long natural history of the disease, a long-term follow-up is needed to provide a better understanding on the implications of such recommendations on disease progression and mortality rates in prostate cancer patients. The future of US screening policy should reflect a targeted 'smarter' screening strategy rather than dichotomizing the decision between 'screen all' or 'screen none'.

Objective: To determine whether the presence of benign glandular tissue at the radical prostatectomy surgical margin is associated with technique (open radical prostatectomy [ORP] or robotic-assisted laparoscopic radical prostatectomy [RALRP]) and if benign glandular tissue increases the risk of biochemical recurrence., Methods: Surgical specimens from men with clinical T1-T2 disease who underwent radical prostatectomy (RP) between 2004 and 2010 were re-reviewed by a single uropathologist, examining all sections from the prostate apex and base for the presence of benign glandular tissue and tumor at the margin. Regression analysis was used to examine associations of benign glandular tissue with surgical approach and biochemical recurrence., Results: Of 934 cases reviewed, 431 were managed by ORP and 503 by RALRP with a median follow-up of 49 and 28 months, respectively. Overall, benign glandular tissue was found in 274 cases (29%): 98 (36%) at the apex, 138 (50%) at the base, and 38 (14%) at both. Compared with those who underwent ORP, patients who underwent RALRP had 3-fold greater odds of benign glandular tissue at the margin (P <.01), including significantly greater number of cases with benign glandular tissue at the base (P <.01). However, recurrence-free survival rates were similar between patients with and without benign glands at the surgical margin (BGM) regardless of surgical approach and across all clinical risk groups (log-rank P = .20)., Conclusion: Patients undergoing RALRP were more likely to have benign glandular tissue at the surgical margin. However, the presence of benign glandular tissue was not an independent risk factor for biochemical recurrence., (Published by Elsevier Inc.)