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BackgroundMagnetic resonance imaging (MRI) is emerging as a robust, noninvasive method for detecting and characterizing prostate cancer (PCa), but limitations remain in its ability to distinguish cancerous from non-cancerous tissue. We evaluated the performance of a novel MRI technique, restriction spectrum imaging (RSI-MRI), to quantitatively detect and grade PCa compared with current standard-of-care MRI.MethodsIn a retrospective evaluation of 33 patients with biopsy-proven PCa who underwent RSI-MRI and standard MRI before radical prostatectomy, receiver-operating characteristic (ROC) curves were performed for RSI-MRI and each quantitative MRI term, with area under the ROC curve (AUC) used to compare each term's ability to differentiate between PCa and normal prostate. Spearman rank-order correlations were performed to assess each term's ability to predict PCa grade in the radical prostatectomy specimens.ResultsRSI-MRI demonstrated superior differentiation of PCa from normal tissue, with AUC of 0.94 and 0.85 for RSI-MRI and conventional diffusion MRI, respectively (P=0.04). RSI-MRI also demonstrated superior performance in predicting PCa aggressiveness, with Spearman rank-order correlation coefficients of 0.53 (P=0.002) and -0.42 (P=0.01) for RSI-MRI and conventional diffusion MRI, respectively, with tumor grade.ConclusionsRSI-MRI significantly improves upon current noninvasive PCa imaging and may potentially enhance its diagnosis and characterization.

Purpose: Diffusion imaging in the prostate is susceptible to distortion from B0 inhomogeneity. Distortion correction in prostate imaging is not routinely performed, resulting in diffusion images without accurate localization of tumors. We performed and evaluated distortion correction for diffusion imaging in the prostate. Materials and methods: 28 patients underwent pre-operative MRI (T2, Gadolinium perfusion, diffusion at b=800s/mm2). The restriction spectrum protocol parameters included b-values of 0, 800, 1500, and 4000s/mm2 in 30 directions for each nonzero b-value. To correct for distortion, forward and reverse trajectories were collected at b=0s/mm2. Distortion maps were generated to reflect the offset of the collected data versus the corrected data. Whole-mount histology was available for correlation. Results: Across the 27 patients evaluated (excluding one patient due to data collection error), the average root mean square distortion distance of the prostate was 3.1. mm (standard deviation, 2.2. mm; and maximum distortion, 12. mm). Conclusion: Improved localization of prostate cancer by MRI will allow better surgical planning, targeted biopsies and image-guided treatment therapies. Distortion distances of up to 12. mm due to standard diffusion imaging may grossly misdirect treatment decisions. Distortion correction for diffusion imaging in the prostate improves tumor localization.

BackgroundStandard magnetic resonance imaging (MRI) of the prostate lacks sensitivity in the diagnosis and staging of prostate cancer (PCa). To improve the operating characteristics of prostate MRI in the detection and characterization of PCa, we developed a novel, enhanced MRI diffusion technique using restriction spectrum imaging (RSI-MRI).MethodsWe compared the efficacy of our novel RSI-MRI technique with standard MRI for detecting extraprostatic extension (EPE) among 28 PCa patients who underwent MRI and RSI-MRI prior to radical prostatectomy, 10 with histologically proven pT3 disease. RSI cellularity maps isolating the restricted isotropic water fraction were reconstructed based on all b-values and then standardized across the sample with z-score maps. Distortion correction of the RSI maps was performed using the alternating phase-encode technique.Results27 patients were evaluated, excluding one patient where distortion could not be performed. Preoperative standard MRI correctly identified extraprostatic the extension in two of the nine pT3 (22%) patients, whereas RSI-MRI identified EPE in eight of nine (89%) patients. RSI-MRI correctly identified pT2 disease in the remaining 18 patients.ConclusionsIn this proof of principle study, we conclude that our novel RSI-MRI technology is feasible and shows promise for substantially improving PCa imaging. Further translational studies of prostate RSI-MRI in the diagnosis and staging of PCa are indicated.

BackgroundKnowledge of factors associated with the course of lower urinary tract symptoms (LUTS) before treatment is needed to inform preventive interventions. In a prospective study of elderly men untreated for LUTS, we identified factors associated with symptom progression and remission.MethodsIn community-dwelling US men aged ≥65 years, the American Urological Association Symptom Index (AUA-SI) was repeated four times, once at baseline (2000-2002) and then every 2 years thereafter. Analyses included 1740 men with all four AUA-SI assessments, who remained free from diagnosed prostate cancer, and who reported no treatment for LUTS or BPH during follow-up that averaged 6.9 (±0.4) years. LUTS change was determined with group-based trajectory modelingof the repeated AUA-SI measures. Multivariable logistic regression was then used to determine the baseline factors associated with progressing compared with stable trajectories, and with remitting compared with progressing trajectories. Lifestyle, body mass index (BMI) (kg/m(2)), mobility, mental health (Short-Form 12), medical history and prescription medications were considered for selection. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for variables in each model.ResultsWe identified 10 AUA-SI trajectories: 4 stable (1277 men, 73%), three progressing (345 men, 20%), two remitting (98 men, 6%) and one mixed (20 men, 1%). Men in progressing compared with stable trajectories were more likely to have mobility limitations (OR=2.0, 95% CI: 1.0-3.8), poor mental health (OR=1.9, 95% CI: 1.1-3.4), BMI≥25.0 kg m(-2) (OR=1.7, 95% CI: 1.0-2.8), hypertension (OR=1.5, 95% CI: 1.0-2.4) and back pain (OR=1.5, 95% CI: 1.0-2.4). Men in remitting compared with progressing trajectories more often used central nervous system medications (OR=2.3, 95% CI: 1.1-4.9) and less often had a history of problem drinking (OR=0.4, 95% CI: 0.2-0.9).ConclusionsSeveral non-urological lifestyle and health factors were independently associated with risk of LUTS progression in older men.

Context: The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer.Objective: To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men.Design, Setting, and Participants: A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011.Interventions: Oral selenium (200 μg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years.Main Outcome Measures: Prostate cancer incidence.Results: This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination.Conclusion: Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.Trial Registration: Clinicaltrials.gov Identifier: NCT00006392. [ABSTRACT FROM AUTHOR]

Context: Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer.Objective: To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men.Design, Setting, and Participants: A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer.Interventions: Oral selenium (200 microg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.Main Outcome Measures: Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer.Results: As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group.Conclusion: Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.Trial Registration: clinicaltrials.gov identifier: NCT00006392. [ABSTRACT FROM AUTHOR]

Objectives: We analyzed the prevalence and characteristics of lower urinary tract symptoms (LUTS) in community-dwelling men aged 80 years and older.Methods: We administered the American Urological Association Symptom Index (AUA-SI) by mail to 291 surviving community-dwelling male participants in the Rancho Bernardo Study, a prospective, community-based study of aging. We compared the prevalence, severity, and types of LUTS occurring in men who were > or = 80 years to those < 80 years.Results: The mean age was 74.6 years (standard deviation [SD] 8.9, range 48.3-97.1). One third of the respondents were > or = 80 years. The mean total AUA-SI score increased steadily by decade of life (P-trend = .002). The prevalence of LUTS was 70% in men > or = 80 years and 56% in men < 80 years (P = .03). Men > or = 80 years had significantly higher mean total AUA-SI (P = .05) and were more likely to complain of incomplete emptying (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.06-4.18, P = .02), frequency (OR 1.83, 95% CI 1.00-3.31, P = .03), urgency (OR 1.76, 95% CI 0.96-3.20, P = .05), and weak stream (OR 1.78, 95% CI 1.01-3.12, P = .03).Conclusions: In this cohort of community-dwelling men, prevalence and severity of LUTS increased into the 10th decade of life. Compared to younger men, men > or = 80 years were more likely to complain of incomplete emptying, frequency, urgency, and weak stream. Further studies of LUTS in older men are needed to better delineate these associations. [ABSTRACT FROM AUTHOR]

Children and adolescents with HIV-1 infection and elevated viral loads are at risk for disease progression. When outpatient adherence efforts fail to reduce viral loads, we have chosen to hospitalize patients for directly observed antiretroviral therapy. A retrospective chart review was performed for patients who were admitted for adherence concerns to a rehabilitation facility from December 1, 2000 to December 1, 2003. Differences in CD4 count and viral load at admission, prior to discharge and 6 months after discharge were evaluated using the Wilcoxon signed-ranks test. Nineteen admissions were included in the analysis. Compared to the mean CD4 count at admission (262), the mean CD4 counts at discharge (492) and 6 months after discharge (429) were significantly higher (p < 0.001 and p = 0.01, respectively). Similar results were observed for change in CD4 percentage. Compared to the mean viral load at admission (log 5.7), the mean viral loads at discharge (log 4.7) and 6 months after discharge (log 5) were significantly lower (p < 0.001 and p < 0.004). The majority of admissions (74%) involved a change in highly active antiretroviral therapy (HAART) regimen. In conclusion, hospitalization for directly observed therapy of HIV-1-infected children and adolescents with elevated viral loads and nonadherence resulted in an immediate and sustained (up to 6 months) reduction in viral load and increase in CD4 count. [ABSTRACT FROM AUTHOR]

Background: There is an unmet clinical need for interventions to prevent disease progression in patients with localized prostate cancer on active surveillance (AS)., Objective: To determine the immunologic response to the PROSTVAC vaccine and the clinical indicators of disease progression in patients with localized prostate cancer on AS., Design, Setting, and Participants: This was a phase 2, double-blind, randomized controlled trial in 154 men with low- or intermediate-risk prostate cancer on AS., Intervention: Participants were randomized (2:1) to receive seven doses of subcutaneous PROSTVAC, a vaccinia/fowlpox viral vector-based immunotherapy containing a prostate-specific antigen (PSA) transgene and three T-cell co-stimulatory molecules, or an empty fowlpox vector (EV) over 140 d., Outcome Measurements and Statistical Analysis: The primary outcome was the change from baseline in CD4 and CD8 T-cell infiltration in biopsy tumor tissue. Key secondary outcomes were safety and changes in prostate biopsy tumor pathology, peripheral antigen-specific T cells, and serum PSA. Continuous variables were compared using nonparametric tests. Categorical variables were compared using Fisher's exact test., Results and Limitations: The PROSTVAC/EV vaccination was well tolerated. All except one participant completed the vaccination series. Changes in CD4 or CD8 density in biopsy tumor tissue did not differ between the PROSTVAC and EV arms. The proportions of patients with Gleason upgrading to grade group 3 after treatment was similar between the arms. There were no differences in postvaccination peripheral T-cell responses or the PSA change from baseline to 6-mo post-treatment follow-up between the groups., Conclusions: In this first-of-kind trial of immunotherapy in patients on AS for prostate cancer, PROSTVAC did not elicit more favorable prostate tissue or peripheral T-cell responses than the EV. There was no difference between the arms in clinicopathologic effects. Despite the null findings, this is the first study reporting the feasibility and acceptability of an immunotherapy intervention in the AS setting., Patient Summary: We looked at responses after an experimental prostate cancer vaccine in patients with prostate cancer on active surveillance (AS). Participants who received the vaccine did not show more favorable outcomes than those receiving the control. Despite these findings, this is the first report showing the feasibility and acceptability of immunotherapy for prostate cancer in patients on AS., (Copyright © 2022 European Association of Urology. All rights reserved.)

Background: Little is known about the true rate of pathogenic (P)/likely pathogenic (LP) germline alterations in Hispanic men with prostate cancer as most studies analyzing the prevalence of P/LP germline alterations were performed in a largely non-Hispanic white population (NHW)., Methods: We performed a retrospective analysis of two separate cohorts of men with prostate cancer: (1) a multicenter cohort of 17,256 men who underwent germline testing in a CLIA-certified laboratory and (2) a single-center cohort of all men eligible for germline testing between 2018 and 2020. The proportions of P/LP alterations and variants of uncertain significance (VUS) were computed. Fisher's exact test was used to compare germline alteration rates for significance. A multivariate logistic regression was performed adjusting for demographic and clinical factors to examine factors associated with germline testing., Results: In the multicenter cohort, the rate of P/LP germline alterations among self-reported Hispanic men was 7.1%, which was lower than self-reported NHW men (9.7% vs. 7.1%, p = 0.058), but was not statistically significant. The VUS rate was significantly higher among the Hispanic cohort (21.5% vs. 16.6%, p = 0.005). In the single-center cohort, 136 Hispanic patients were eligible for testing of which 34 underwent germline testing (26.1%, N = 34/136). Of all prostate cancer patients in the single-center cohort undergoing germline testing (n = 173), the rate of P/LP alterations in Hispanic patients was not significantly different compared to NHW patients (14.7% vs. 12.2%, p = 0.77). The rate of VUS in Hispanic patients was significantly higher than that of NHW patients (20.6% vs. 7.2%, p = 0.047)., Conclusion: The P/LP germline alteration rate in our cohorts was similar between Hispanic and NHW men. The rate of VUS was significantly higher in Hispanic men, a consequence of undertesting in minority populations. These data support that Hispanic men with prostate cancer should be screened for germline testing similar to NHW men., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Despite higher risks associated with prostate cancer, young African American men are poorly represented in prostate-specific antigen (PSA) trials, which limits proper evidence-based guidance. We evaluated the impact of PSA screening, alongside primary care provider utilization, on prostate cancer outcomes for these patients., Methods: We identified African American men aged 40-55 years, diagnosed with prostate cancer between 2004 and 2017 within the Veterans Health Administration. Inverse probability of treatment-weighted propensity scores were used in multivariable models to assess PSA screening on PSA levels higher than 20, Gleason score of 8 or higher, and metastatic disease at diagnosis. Lead-time adjusted Fine-Gray regression evaluated PSA screening on prostate cancer-specific mortality (PCSM), with noncancer death as competing events. All statistical tests were 2-sided., Results: The cohort included 4726 patients. Mean age was 51.8 years, with 84-month median follow-up. There were 1057 (22.4%) with no PSA screening prior to diagnosis. Compared with no screening, PSA screening was associated with statistically significantly reduced odds of PSA levels higher than 20 (odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.49 to 0.63; P < .001), Gleason score of 8 or higher (OR = 0.78, 95% CI = 0.69 to 0.88; P < .001), and metastatic disease at diagnosis (OR = 0.50, 95% CI = 0.39 to 0.64; P < .001), and decreased PCSM (subdistribution hazard ratio = 0.52, 95% CI = 0.36 to 0.76; P  < .001). Primary care provider visits displayed similar effects., Conclusions: Among young African American men diagnosed with prostate cancer, PSA screening was associated with statistically significantly lower risk of PSA levels higher than 20, Gleason score of 8 or higher, and metastatic disease at diagnosis and statistically significantly reduced risk of PCSM. However, the retrospective design limits precise estimation of screening effects. Prospective studies are needed to validate these findings., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: This study was done to determine the representation of minorities, women, and the elderly in National Cancer Institute (NCI) clinical trials., Methods: This is an analysis in the NCI Clinical Data Update System. Patients were evaluated in breast, colorectal, lung, and prostate cancer trials from 2000 to 2019. Representation in a trial was determined by race/ethnicity, sex, and age. Secondarily, the change in trial participation by multivariable analysis by comparing years 2000 through 2004 to 2015 through 2019 was evaluated., Results: The cohort included 242,720 participants: 197,320 Non-Hispanic White (81.3%), 21,190 Black (8.7%), 11,587 Hispanic (4.8%), and 6880 Asian/Pacific Islander (2.8%). Black and Hispanic patients were underrepresented for colorectal (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.50-0.67; P < .001 and OR, 0.74; 95% CI, 0.64-0.87; P < .001, respectively), lung (OR, 0.83; 95% CI, 0.76-0.91; P < .001 and 0.66; 95% CI, 0.57-0.77; P < .001, respectively), and prostate cancer trials (OR, 0.85; 95% CI, 0.79-0.92; P < .001 and OR, 0.58; 95% CI, 0.51-0.66; P < .001) between 2015 and 2019. The odds of participation in 2015 to 2019 increased among Black patients in breast (OR, 2.19; 95% CI, 2.07-%2.32; P < .001), lung (OR, 1.54; 95% CI, 1.38-1.73; P < .001), and prostate cancer trials (OR, 1.14; 95% CI, 1.04-1.26; P < .001). The odds of participation in a trial among Hispanic patients increased for breast (OR, 3.32; 95% CI, 3.09-3.56; P < .001), colorectal (OR, 2.46; 95% CI, 2.04-2.96; P < .001), lung (OR, 3.88; 95% CI, 3.20-4.69; P < .001), and prostate cancer (OR, 1.70; 95% CI, 1.42-2.04; P = .005)., Conclusions: This study identified that Black and Hispanic patients remain underrepresented in trials, but in recent years, participation has increased. These findings indicate that minority participation has increased over time, but further efforts are needed., (© 2021 American Cancer Society.)

There is growing evidence that the microbiome is involved in development and treatment of many human diseases, including prostate cancer. There are several potential pathways for microbiome-based mechanisms for the development of prostate cancer: direct impacts of microbes or microbial products in the prostate or the urine, and indirect impacts from microbes or microbial products in the gastrointestinal tract. Unique microbial signatures have been identified within the stool, oral cavity, tissue, urine, and blood of prostate cancer patients, but studies vary in their findings. Recent studies describe potential diagnostic and therapeutic applications of the microbiome, but further clinical investigation is needed. In this review, we explore the existing literature on the discovery of the human microbiome and its relationship to prostate cancer., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Active surveillance (AS) is a safe treatment option for men with low-risk, localized prostate cancer. However, the safety of AS for patients with intermediate-risk prostate cancer remains unclear., Patients and Methods: We identified men with NCCN-classified low-risk and favorable and unfavorable intermediate-risk prostate cancer diagnosed between 2001 and 2015 and initially managed with AS in the Veterans Health Administration. We analyzed progression to definitive treatment, metastasis, prostate cancer-specific mortality (PCSM), and all-cause mortality using cumulative incidences and multivariable competing-risks regression., Results: The cohort included 9,733 men, of whom 1,007 (10.3%) had intermediate-risk disease (773 [76.8%] favorable, 234 [23.2%] unfavorable), followed for a median of 7.6 years. The 10-year cumulative incidence of metastasis was significantly higher for patients with favorable (9.6%; 95% CI, 7.1%-12.5%; P<.001) and unfavorable intermediate-risk disease (19.2%; 95% CI, 13.4%-25.9%; P<.001) than for those with low-risk disease (1.5%; 95% CI, 1.2%-1.9%). The 10-year cumulative incidence of PCSM was also significantly higher for patients with favorable (3.7%; 95% CI, 2.3%-5.7%; P<.001) and unfavorable intermediate-risk disease (11.8%; 95% CI, 6.8%-18.4%; P<.001) than for those with low-risk disease (1.1%; 95% CI, 0.8%-1.4%). In multivariable competing-risks regression, favorable and unfavorable intermediate-risk patients had significantly increased risks of metastasis and PCSM compared with low-risk patients (all P<.001)., Conclusions: Compared with low-risk patients, those with favorable and unfavorable intermediate-risk prostate cancer managed with AS are at increased risk of metastasis and PCSM. AS may be an appropriate option for carefully selected patients with favorable intermediate-risk prostate cancer, though identification of appropriate candidates and AS protocols should be tested in future prospective studies.

Objective: To analyse the effect of age at diagnosis on clinical outcomes of localized prostate cancer (PCa) treated with radiation therapy., Subjects and Methods: We identified 12 784 patients with intermediate- or high-risk localized PCa treated with radiation therapy (RT) and neoadjuvant androgen deprivation therapy (ADT) between 2000 and 2015 from nationwide Veterans Affairs data. Patients were grouped into three age categories (≤59, 60-69, and ≥70 years old). Outcomes included immediate PSA response (3-month post-RT PSA and 2-year PSA nadir, grouped into <0.10 ng/ml, 0.10-0.49 ng/ml, and ≥0.50 ng/ml), biochemical recurrence, and PCa-specific mortality. Multivariable regression models included ordinal logistic regression for short-term PSA outcomes, Cox regression for biochemical recurrence, and Fine-Gray competing risks regression for PCa-specific mortality., Results: A total of 2136 patients (17%) were ≤59 years old at diagnosis, 6107 (48%) were 60-69 years old, and 4541 (36%) were ≥70 years old. Median follow-up was 6.3 years. Younger age was associated with greater odds of higher 3-month PSA group (≤59 vs. ≥70: adjusted odds ratio [aOR] 1.90, 95% CI 1.64-2.20; p  < 0.001) and higher 2-year PSA nadir group (≤59 vs. ≥70: aOR 1.89, 95% CI 1.62-2.19, p  < 0.001). Younger age was associated with greater risk of biochemical recurrence (≤59 vs. ≥70: adjusted hazard ratio 1.45, 95% CI 1.26-1.67, p  < 0.001) but not PCa-specific mortality ( p  = 0.16)., Conclusion: In a large nationwide sample of US veterans treated with ADT and RT for localized PCa, younger age was associated with inferior short-term PSA response and higher risk of biochemical recurrence., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Background: The safety of active surveillance (AS) for African American men compared with non-Hispanic White (White) men with intermediate-risk prostate cancer is unclear., Methods: The authors identified patients with modified National Comprehensive Cancer Network favorable ("low-intermediate") and unfavorable ("high-intermediate") intermediate-risk prostate cancer diagnosed between 2001 and 2015 and initially managed with AS in the Veterans Health Administration database. They analyzed definitive treatment, disease progression, metastases, prostate cancer-specific mortality (PCSM), and all-cause mortality by using cumulative incidences and multivariable competing-risks (disease progression, metastasis, and PCSM) or Cox (all-cause mortality) regression., Results: The cohort included 1007 men (African Americans, 330 [32.8%]; Whites, 677 [67.2%]) followed for a median of 7.7 years; 773 (76.8%) had low-intermediate-risk disease, and 234 (23.2%) had high-intermediate-risk disease. The 10-year cumulative incidences of definitive treatment were not significantly different (African Americans, 83.5%; 95% confidence interval [CI], 78.5%-88.7%; Whites, 80.6%; 95% CI, 76.6%-84.4%; P = .17). Among those with low-intermediate-risk disease, there were no significant differences in the 10-year cumulative incidences of disease progression (African Americans, 46.8%; 95% CI, 40.0%-53.3%; Whites, 46.9%; 95% CI, 42.1%-51.5%; P = .91), metastasis (African Americans, 7.1%; 95% CI, 3.7%-11.8%; Whites, 10.8%; 95% CI, 7.6%-14.6%; P = .17), or PCSM (African Americans, 3.8%; 95% CI, 1.6%-7.5%; Whites, 3.8%; 95% CI, 2.0%-6.3%; P = .69). In a multivariable regression including the entire cohort, African American race was not associated with increased risks of definitive treatment, disease progression, metastasis, PCSM, or all-cause mortality (all P > .30)., Conclusions: Outcomes in the Veterans Affairs Health System were similar for African American and White men treated for low-intermediate-risk prostate cancer with AS., (© 2021 American Cancer Society.)

Purpose: Benign prostatic hyperplasia (BPH) is a histologic diagnosis describing proliferation of smooth muscle and epithelial cells within the prostatic transition zone. The prevalence and severity of lower urinary tract symptoms (LUTS) in aging men are progressive and impact the health and welfare of society. This revised Guideline provides a useful reference on effective evidence-based management of male LUTS/BPH. See the accompanying algorithm for a summary of the procedures detailed in the Guideline (figures 1 and 2[Figure: see text][Figure: see text])., Materials and Methods: The Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, Cochrane Library, and AHRQ databases to identify eligible English language studies published between January 2008 and April 2019, then updated through December 2020. Search terms included Medical Subject Headings (MeSH) and keywords for pharmacological therapies, drug classes, and terms related to LUTS or BPH. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text])., Results: Nineteen guideline statements pertinent to evaluation, work-up, and medical management were developed. Appropriate levels of evidence and supporting text were created to direct both primary care and urologic providers towards streamlined and suitable practices., Conclusions: The work up and medical management of BPH requires attention to individual patient characteristics, while also respecting common principles. Clinicians should adhere to recommendations and familiarize themselves with standards of BPH management.

Purpose: Surgical therapies for symptomatic bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) are many, and vary from minimally invasive office based to high-cost operative approaches. This Guideline presents effective evidence-based surgical management of male lower urinary tract symptoms secondary/attributed to BPH (LUTS/BPH). See accompanying algorithm for a detailed summary of procedures (figure[Figure: see text])., Materials/methods: The Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, Cochrane Library, and AHRQ databases to identify eligible studies published between January 2007 and September 2020, which includes the initial publication (2018) and amendments (2019, 2020). The Team also reviewed articles identified by Guideline Panel Members. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, information is provided as Clinical Principles and Expert Opinions (table[Table: see text])., Results: Twenty-four guideline statements pertinent to pre-operative and surgical management were developed. Appropriate levels of evidence and supporting text were created to direct urologic providers towards suitable and safe operative interventions for individual patient characteristics. A re-treatment section was created to direct attention to longevity and outcomes with individual approaches to help guide patient counselling and therapeutic decisions., Conclusion: Pre-operative and surgical management of BPH requires attention to individual patient characteristics and procedural risk. Clinicians should adhere to recommendations and familiarize themselves with criteria that yields the highest likelihood of surgical success when choosing a particular approach for a particular patient.

Purpose: Men with low serum testosterone at the time of prostate cancer diagnosis are frequently considered to have more aggressive disease. We examined treatment outcomes in men with clinically localized high-risk cancer to determine if baseline testosterone level identified men at higher risk for cancer progression after treatment., Materials and Methods: Alliance/CALGB 90203 randomized men with clinically localized high-risk prostate cancer to radical prostatectomy alone or neoadjuvant chemohormonal therapy and radical prostatectomy. Men with available baseline testosterone levels who had not received androgen deprivation prior to study enrollment were studied (656). Testosterone level was examined as a continuous variable, as quartiles, and separately in men with an absolute testosterone level above/below 150 ng/dl. Outcomes evaluated were overall survival and event-free survival with events defined by biochemical recurrence, secondary treatment, prostate cancer metastasis, and death., Results: We were unable to demonstrate a difference between baseline serum testosterone level measured as a continuous variable, as quartiles, or as a dichotomous variable (above/below 150 ng/dl) with the outcomes measured. This finding was observed in both arms of the study., Conclusions: Baseline serum testosterone level did not predict outcomes in men with clinically localized high-risk prostate cancer treated with radical prostatectomy alone or neoadjuvant chemohormonal therapy and radical prostatectomy.

Purpose: This multicenter randomized phase 2 trial investigates the impact of intense androgen deprivation on radical prostatectomy pathologic response and radiographic and tissue biomarkers in localized prostate cancer (NCT02903368)., Materials and Methods: Eligible patients had a Gleason score ≥4+3=7, prostate specific antigen >20 ng/mL or T3 disease and lymph nodes <20 mm. In Part 1, patients were randomized 1:1 to apalutamide, abiraterone acetate, prednisone and leuprolide (AAPL) or abiraterone, prednisone, leuprolide (APL) for 6 cycles (1 cycle=28 days) followed by radical prostatectomy. Surgical specimens underwent central review. The primary end point was the rate of pathologic complete response or minimum residual disease (minimum residual disease, tumor ≤5 mm). Secondary end points included prostate specific antigen response, positive margin rate and safety. Magnetic resonance imaging and tissue biomarkers of pathologic outcomes were explored., Results: The study enrolled 118 patients at 4 sites. Median age was 61 years and 94% of patients had high-risk disease. The combined pathologic complete response or minimum residual disease rate was 22% in the AAPL arm and 20% in the APL arm (difference: 1.5%; 1-sided 95% CI -11%, 14%; 1-sided p=0.4). No new safety signals were observed. There was low concordance and correlation between posttherapy magnetic resonance imaging assessed and pathologically assessed tumor volume. PTEN-loss, ERG positivity and presence of intraductal carcinoma were associated with extensive residual tumor., Conclusions: Intense neoadjuvant hormone therapy in high-risk prostate cancer resulted in favorable pathologic responses (tumor < 5 mm) in 21% of patients. Pathologic responses were similar between treatment arms. Part 2 of this study will investigate the impact of adjuvant hormone therapy on biochemical recurrence.

Importance: The association of the Patient Protection and Affordable Care Act (ACA) with insurance status and cancer stage at diagnosis among patients with renal cell carcinoma (RCC) is unknown., Objective: To test the hypothesis that the ACA may be associated with increased access to care through expansion of insurance, which may vary based on income., Design, Setting, and Participants: This retrospective cohort analysis included patients diagnosed with RCC from January 1, 2010, to December 31, 2016, in the National Cancer Database. Data were analyzed from July 1 to December 31, 2020. The periods from 2010 to 2013 and from 2014 to 2016 were defined as pre- and post-ACA implementation, respectively. Patients were categorized as living in a Medicaid expansion state or not., Exposures: Implementation of the ACA., Main Outcomes and Measures: The absolute percentage change (APC) of insurance coverage was calculated before and after ACA implementation in expansion and nonexpansion states. Secondary outcomes included change in stage at diagnosis, difference in the rate of insurance change, and change in localized disease between expansion and nonexpansion states. Adjusted difference-in-difference modeling was performed., Results: The cohort included 78 099 patients (64.7% male and 35.3% female; mean [SD] age, 54.66 [6.46] years), of whom 21.2% had low, 46.2% had middle, and 32.6% had high incomes. After ACA implementation, expansion states had a lower proportion of uninsured patients (adjusted difference-in-difference, -1.14% [95% CI, -1.98% to -1.41%]; P = .005). This occurred to the greatest degree among low-income patients through the acquisition of Medicaid (APC, 11.0% [95% CI, 8.6%-13.3%]; P < .001). Implementation of the ACA was also associated with an increase in detection of stage I and II disease (APC, 4.0% [95% CI, 1.6%-6.3%]; P = .001) among low-income patients in expansion states., Conclusions and Relevance: Among patients with RCC, ACA implementation was associated with an increase in insurance coverage status in both expansion and nonexpansion states for all income groups, but to a greater degree in expansion states. The proportion of patients with localized disease increased among low-income patients in both states. These data suggest that ACA implementation is associated with earlier RCC detection among lower-income patients.

Importance: The association of prostate-specific antigen velocity (PSAV) with clinical progression in patients with localized prostate cancer managed with active surveillance remains unclear and, to our knowledge, has not been studied in African American patients., Objectives: To test the hypothesis that PSAV is associated with clinical progression in patients with low-risk prostate cancer treated with active surveillance and to identify differences between African American and non-Hispanic White patients., Design, Setting, and Participants: This was a retrospective population-based cohort study using patient records from the Veterans Heath Administration Informatics and Computing Infrastructure on 5296 patients with a diagnosis of localized prostate cancer from January 1, 2001, to December 31, 2015, who were managed with active surveillance. Follow-up extended through March 31, 2020. Low-risk prostate cancer was defined as International Society of Urologic Pathology grade group (GG) 1 clinical tumor stage 2A or lower, PSA level of 10 ng/dL or lower, active surveillance, and no definitive treatment within the first year after diagnosis with at least 1 additional staging biopsy after diagnostic biopsy., Exposures: Prostate-specific antigen testing., Main Outcomes and Measures: The primary outcome was GG progression detected after repeated biopsy or prostatectomy, defined as GG2 or higher or GG3 or higher. The secondary outcome was incident metastases. Cumulative incidence functions and multivariable Cox proportional hazards regression models were used to test associations between PSAV and outcomes., Results: The final cohort (n = 5296) included 3919 non-Hispanic White men (74.0%; mean [SD] age, 65.7 [5.8] years) and 1377 African American men (26.0%; mean [SD] age, 62.8 [6.6] years). Compared with African American patients, non-Hispanic White patients were older (mean [SD] age, 65.7 [5.8] years vs 62.8 [6.6] years; P < .001), presented with higher cT stage (stage T2, 608 [15.5%] vs 111 [8.1%]; P < .001), had a higher Charlson Comorbidity Index score (1 and ≥2, 912 [23.3%] vs 273 [19.8%]; P = .002), had higher median income ($60 000 to ≥$100 000, 1223 [31.2%] vs 282 [20.5%]; P < .001), and had a higher median level of education (20% to ≥30% with college degree, 1192 [30.4%] vs 333 [24.2%]; P < .001). Progression to GG2 or higher occurred in 2062 patients (38.9%), with a cumulative incidence of 43.2%, and progression to GG3 or higher occurred in 728 patients (13.7%). Fifty-four patients (1.0%) developed metastases. On multivariable analysis, PSAV was significantly associated with progression to GG2 (hazard ratio, 1.32 [95% CI, 1.26-1.39]), GG3 (hazard ratio, 1.51 [95% CI, 1.41-1.62]), and metastases (hazard ratio, 1.38 [95% CI, 1.10-1.74]). Optimal PSAV thresholds that were associated with progression were significantly lower for African American patients (0.44 ng/mL/y) compared with non-Hispanic White patients (1.18 ng/mL/y)., Conclusions and Relevance: This study suggests that PSAV is significantly associated with grade progression among patients with low-risk prostate cancer managed with active surveillance, but at lower values for African American patients compared with non-Hispanic White patients. These data suggest that serial PSA measures may potentially substitute for multiple prostate biopsies and that African American patients may merit increased frequency of PSA testing.

Background: The safety of testosterone therapy (TT) after definitive treatment for localized prostate cancer remains undefined. We analyzed the risks of biochemical recurrence and mortality in men receiving TT after treatment for localized prostate cancer., Methods: Cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure. We identified 69,984 patients with localized prostate cancer diagnosed from 2001 to 2015 treated with surgery or radiation. We coded receipt of TT after treatment as a time-dependent covariate; used the National Death Index to identify cause of death; and defined biochemical recurrence as PSA > 0.2 ng/mL after surgery and nadir + 2 ng/mL after radiation. We analyzed recurrence and mortality using cumulative incidence curves, Fine-Gray competing risk regression, and Cox regression., Results: This cohort included 28,651 surgery patients and 41,333 radiation patients, of whom 469 (1.64%) and 543 (1.31%), respectively, received TT with a median follow-up of 6.95 years. Comparing testosterone users to nonusers, there were no between-group differences in biochemical recurrence, prostate cancer-specific mortality, or overall mortality after surgery [hazard ratios (HR): 1.07; HR: 0.72 (p = 0.43); and HR: 1.11 (p = 0.43), respectively] or radiation [HR: 1.07; HR: 1.02 (p = 0.95); and HR: 1.02 (p = 0.86), respectively]. Limitations included lack of detailed data on TT duration and serum testosterone concentrations., Conclusions: In this multi-ethnic national cohort, TT did not increase the risks of biochemical recurrence or prostate cancer-specific or overall mortality after surgery or radiation. These data suggest that TT is safe in appropriate men after definitive treatment of localized prostate cancer.

Background: There is concern that African-American men (AA) with low-risk prostate cancer may present with more aggressive disease and thus may not be candidates for active surveillance (AS). However, it is uncertain if poorer outcomes are due to disparities in access to medical care rather than true biological differences., Methods: Observational cohort study of patients diagnosed with low-risk PC-Gleason score ≤6, clinical tumor stage ≤2A, and prostate specific antigen (PSA) level ≤10-at US Department of Veterans Affairs between January 1, 2001 and October 31, 2015 and treated with radical prostatectomy. Outcomes included upgrading to Gleason Grade Group 2 (GG2), GG ≥ 3, PSA recurrence, pathologic tumor stage ≥3, positive surgical margins, and all-cause mortality., Results: A total of 2857 men (AA: 835 White: 2022) with a median follow-up of 7.1 years. Overall, there was no significant difference between AA and White men in upgrading to GG ≥ 3 (RR = 1.18, p = 0.43), tumor stage ≥3 (RR = 0.95, p = 0.74), positive surgical margins (RR = 1.14, p = 0.20), PSA recurrence (SHR = 1.26, p = 0.06), and all-cause mortality (SHR = 1.26, p = 0.16). However, there was a significant increase in upgrading for AA to GG2 (RR = 1.49, p < 0.01)., Conclusions: There was no significant difference in most adverse pathologic outcomes between AA and White patients. However, GG2 upgrading was more common in AA men. The implication is that AA may need to undergo additional evaluation, such as a biopsy MRI, before initiating AS. Whether the increase in GG2 upgrading will lead to poorer long-term clinical outcomes such as metastasis and PCSM also requires further investigation.

Importance: There is concern that African American men with low-risk prostate cancer may harbor more aggressive disease than non-Hispanic White men. Therefore, it is unclear whether active surveillance is a safe option for African American men., Objective: To compare clinical outcomes of African American and non-Hispanic White men with low-risk prostate cancer managed with active surveillance., Design, Setting, and Participants: Retrospective cohort study in the US Veterans Health Administration Health Care System of African American and non-Hispanic White men diagnosed with low-risk prostate cancer between January 1, 2001, and December 31, 2015, and managed with active surveillance. The date of final follow-up was March 31, 2020., Exposures: Active surveillance was defined as no definitive treatment within the first year of diagnosis and at least 1 additional surveillance biopsy., Main Outcomes and Measures: Progression to at least intermediate-risk, definitive treatment, metastasis, prostate cancer-specific mortality, and all-cause mortality., Results: The cohort included 8726 men, including 2280 African American men (26.1%) (median age, 63.2 years) and 6446 non-Hispanic White men (73.9%) (median age, 65.5 years), and the median follow-up was 7.6 years (interquartile range, 5.7-9.9; range, 0.2-19.2). Among African American men and non-Hispanic White men, respectively, the 10-year cumulative incidence of disease progression was 59.9% vs 48.3% (difference, 11.6% [95% CI, 9.2% to 13.9%); P < .001); of receipt of definitive treatment, 54.8% vs 41.4% (difference, 13.4% [95% CI, 11.0% to 15.7%]; P < .001); of metastasis, 1.5% vs 1.4% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .49); of prostate cancer-specific mortality, 1.1% vs 1.0% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .82); and of all-cause mortality, 22.4% vs 23.5% (difference, 1.1% [95% CI, -0.9% to 3.1%]; P = 0.09)., Conclusions and Relevance: In this retrospective cohort study of men with low-risk prostate cancer followed up for a median of 7.6 years, African American men, compared with non-Hispanic White men, had a statistically significant increased 10-year cumulative incidence of disease progression and definitive treatment, but not metastasis or prostate cancer-specific mortality. Longer-term follow-up is needed to better assess the mortality risk.

Cancer vaccines, cytokines, and checkpoint inhibitors are immunotherapeutic agents that act within the cancer immunity cycle. Prostate cancer has provided unique opportunities for, and challenges to, immunotherapy drug development, including low tumor mutational burdens, limited expression of PD-L1, and minimal T-cell intratumoral infiltrates. Nevertheless, efforts are ongoing to help prime prostate tumors by turning a "cold" prostate cancer "hot" and thus rendering them more susceptible to immunotherapy. Combination treatments, use of molecular biomarkers, and use of new immunotherapeutic agents provide opportunities to enhance the immune response to prostate tumors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The AUA Guideline panel provides evidence-based recommendations for the surgical management of male lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH)., Materials and Methods: The Panel amended the Guideline in 2020 to reflect additional literature published through September 2019. When sufficient evidence existed, the Panel assigned the body of evidence a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, the Panel provided additional information as Clinical Principles and Expert Opinions (See table 1[Table: see text])., Results: Amendments to these Guidelines include: 1) an amended statement (Guideline 1) to include conducting a physical examination; 2) a new statement (Guideline 6) discussing concepts of treatment failure and retreatment; 3) an amended statement (Guideline 15) with updated supporting text for prostatic urethral lift (PUL); 4) an amended statement (Guideline 16) for PUL; 5) an amended statement (Guideline 17) with updated supporting text for transurethral microwave therapy (TUMT); 6) an amended statement (Guideline 18) with updated supporting text for water vapor thermal therapy; 7) updated supporting text for water vapor thermal therapy (Guideline 19); 8) an amended statement (Guideline 21) with updated supporting text for laser enucleation; 9) an amended statement (Guideline 22) with updated supporting text for Aquablation; and 10) an amended statement (Guideline 23) with updated supporting text for Prostate Artery Embolization (PAE)., Conclusions: These evidence-based updates to the AUA Guidelines further inform the surgical management of LUTS/BPH.

Purpose: Radical prostatectomy (RP) alone is often inadequate in curing men with clinically localized, high-risk prostate cancer (PC). We hypothesized that chemohormonal therapy (CHT) with androgen-deprivation therapy plus docetaxel before RP would improve biochemical progression-free survival (BPFS) over RP alone., Patients and Methods: Men with clinically localized, high-risk PC were assigned to RP alone or neoadjuvant CHT with androgen deprivation plus docetaxel (75 mg/m 2 body surface area every 3 weeks for 6 cycles) and RP. The primary end point was 3-year BPFS. Biochemical failure was defined as a serum prostate-specific antigen level > 0.2 ng/mL that increased on 2 consecutive occasions that were at least 3 months apart. Secondary end points included 5-year BPFS, overall BPFS, local recurrence, metastasis-free survival (MFS), PC-specific mortality, and overall survival (OS)., Results: In total, 788 men were randomly assigned. Median follow-up time was 6.1 years. The overall rates of grade 3 and 4 adverse events during chemotherapy were 26% and 19%, respectively. No difference was seen in 3-year BPFS between neoadjuvant CHT plus RP and RP alone (0.89 v 0.84, respectively; 95% CI for the difference, -0.01 to 0.11; P = .11). Neoadjuvant CHT was associated with improved overall BPFS (hazard ratio [HR], 0.69; 95% CI, 0.48 to 0.99), improved MFS (HR, 0.70; 95% CI, 0.51 to 0.95), and improved OS (HR, 0.61; 95% CI, 0.40 to 0.94) compared with RP alone., Conclusion: The primary study end point, 3-year BPFS, was not met. Although some improvement was seen in secondary end points, any potential benefit must be weighed against toxicity. Our data do not support the routine use of neoadjuvant CHT and RP in patients with clinically localized, high-risk PC at this time., Competing Interests: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Background: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening., Methods: United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score ≥7, stage T3-T4, PSA ≥10, or nodal/distant metastases). Using HRs estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age, when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-year-standard risk), was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups., Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-year-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age., Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS., Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions., (©2020 American Association for Cancer Research.)

Purpose: Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services., Methods: A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider)., Results: Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM , for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM , and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches., Conclusion: This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.

Survivorship care for patients with prostate cancer requires careful consideration of unique disease-specific factors, including the prolonged natural disease history, the potential for competing health risks, and the consequences of long-term androgen deprivation therapy. However, current prostate cancer survivorship research is unfortunately limited by the lack of a robust supportive evidence base, variability in the definitions and measurement of survivorship outcomes, and a heavy reliance on expert opinion. As a result, the conduct of quality prostate cancer survivorship research is of increasing importance for patients, medical providers, and other key stakeholders. This manuscript harmonizes a path forward for improving prostate cancer survivorship by defining prostate cancer survivorship and survivorship research, as well as by highlighting key research priorities and cooperative mechanisms for survivorship studies within prostate cancer, with a particular focus on men with advanced disease., (Copyright © 2019. Published by Elsevier Inc.)

Importance: Guidelines endorsing vegetable-enriched diets to improve outcomes for prostate cancer survivors are based on expert opinion, preclinical studies, and observational data., Objective: To determine the effect of a behavioral intervention that increased vegetable intake on cancer progression in men with early-stage prostate cancer., Design, Setting, and Participants: The Men's Eating and Living (MEAL) Study (CALGB 70807 [Alliance]) was a randomized clinical trial conducted at 91 US urology and medical oncology clinics that enrolled 478 men aged 50 to 80 years with biopsy-proven prostate adenocarcinoma (International Society of Urological Pathology grade group = 1 in those <70 years and ≤2 in those ≥70 years), stage cT2a or less, and serum prostate-specific antigen (PSA) level less than 10 ng/mL. Enrollment occurred from January 2011 to August 2015; 24-month follow-up occurred from January 2013 to August 2017., Interventions: Patients were randomized to a counseling behavioral intervention by telephone promoting consumption of 7 or more daily vegetable servings (MEAL intervention; n = 237) or a control group, which received written information about diet and prostate cancer (n = 241)., Main Outcomes and Measures: The primary outcome was time to progression; progression was defined as PSA level of 10 ng/mL or greater, PSA doubling time of less than 3 years, or upgrading (defined as increase in tumor volume or grade) on follow-up prostate biopsy., Results: Among 478 patients randomized (mean [SD] age, 64 [7] years; mean [SD] PSA level, 4.9 [2.1] ng/mL), 443 eligible patients (93%) were included in the primary analysis. There were 245 progression events (intervention: 124; control: 121). There were no significant differences in time to progression (unadjusted hazards ratio, 0.96 [95% CI, 0.75 to 1.24]; adjusted hazard ratio, 0.97 [95% CI, 0.76 to 1.25]). The 24-month Kaplan-Meier progression-free percentages were 43.5% [95% CI, 36.5% to 50.6%] and 41.4% [95% CI, 34.3% to 48.7%] for the intervention and control groups, respectively (difference, 2.1% [95% CI, -8.1% to 12.2%])., Conclusions and Relevance: Among men with early-stage prostate cancer managed with active surveillance, a behavioral intervention that increased vegetable consumption did not significantly reduce the risk of prostate cancer progression. The findings do not support use of this intervention to decrease prostate cancer progression in this population, although the study may have been underpowered to identify a clinically important difference., Trial Registration: ClinicalTrials.gov Identifier: NCT01238172.

Patients with high-risk localized prostate cancer benefit from multimodality therapy of curative intent. Androgen-deprivation therapy (ADT) combined with radiation improves survival in this population. However, prior clinical trials of neoadjuvant ADT and surgery failed to consistently demonstrate a survival advantage. The development of novel, more potent hormonal agents presents an opportunity to revisit the potential for neoadjuvant therapy to improve long-term outcomes for patients with localized prostate cancer. We review recent advances in neoadjuvant approaches for prostate cancer and emerging clinical trials data supporting the use of neoadjuvant therapy prior to radical prostatectomy.

Context: Prostate-specific antigen (PSA) changes during testosterone treatment of older hypogonadal men have not been rigorously evaluated., Design: Double-blinded, placebo-controlled trial., Setting: Twelve US academic medical centers., Participants: Seven hundred ninety hypogonadal men ≥65 years of age with average testosterone levels ≤275 ng/dL. Men at high risk for prostate cancer were excluded., Interventions: Testosterone or placebo gel for 12 months., Main Outcomes: Percentile changes in PSA during testosterone treatment of 12 months., Results: Testosterone treatment that increased testosterone levels from 232 ± 63 ng/dL to midnormal was associated with a small but substantially greater increase (P < 0.001) in PSA levels than placebo treatment. Serum PSA levels increased from 1.14 ± 0.86 ng/mL (mean ± SD) at baseline by 0.47 ± 1.1 ng/mL at 12 months in the testosterone group and from 1.25 ± 0.86 ng/mL by 0.06 ± 0.72 ng/mL in the placebo group. Five percent of men treated with testosterone had an increase ≥1.7 ng/mL and 2.5% of men had an increase of ≥3.4 ng/mL. A confirmed absolute PSA >4.0 ng/mL at 12 months was observed in 1.9% of men in the testosterone group and 0.3% in the placebo group. Four men were diagnosed with prostate cancer; two were Gleason 8., Conclusions: When hypogonadal older men with normal baseline PSA are treated with testosterone, 5% had an increase in PSA ≥1.7 ng/mL, and 2.5% had an increase ≥3.4 ng/mL., (Copyright © 2019 Endocrine Society.)