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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.)

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.

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.)

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: 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.

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.

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.)