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Background: Prostate cancer (PCa) screening recommendations do not support prostate-specific antigen (PSA) screening for older men. Such screening often occurs, however. It is, therefore, important to understand how frequently and among which subgroups screening occurs, and the extent of distant stage PCa diagnoses among screened older men., Methods: Using the 2014-2016 linked Ohio Cancer Incidence Surveillance System (OCISS) and Medicare administrative database, we identified men 68 and older diagnosed with PCa and categorized their PSA testing in the three years preceding diagnosis as screening or diagnostic. We conducted multivariable logistic regression analysis to identify correlates of screening PSA and to determine whether screening PSA is independently associated with distant stage disease., Results: Our study population included 3034 patients (median age: 73 years). 62.1% of PCa patients underwent at least one screening-based PSA in the three years preceding diagnosis. Older age (75-84 years: aOR [95% CI]: 0.84 [0.71, 0.99], ≥ 85: aOR: 0.27 [0.19, 0.38]), and frailty (aOR: 0.51 [0.37, 0.71]) were associated with lower screening. Screening was associated with decreased odds of distant stage disease (aOR: 0.55 [0.42, 0.71]). However, older age (75-84 years: aOR: 2.43 [1.82, 3.25], ≥ 85: aOR: 10.57 [7.05, 15.85]), frailty (aOR: 5.00 [2.78, 9.31]), and being separated or divorced (aOR: 1.64 [1.01, 2.60]) were associated with increased distant stage PCa., Conclusion: PSA screening in older men is common, though providers appear to curtail PSA screening as age and frailty increase. Screened older men are diagnosed at earlier stages, but the harms of screening cannot be assessed., Competing Interests: Declarations Conflict of interest The authors declare no competing interests. Ethical approval This study was approved by the Case Western Reserve University Institutional Review Board (#20120107), the Ohio Department of Health Institutional Review Board (#2018-05), and the Centers for Medicare and Medicaid Services Privacy board (DUA# 2012-23469)., (© 2024. The Author(s).)

BACKGROUND: The Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) working group identified metastasis-free survival as a valid surrogate end point for overall survival (OS) for patients with localized prostate cancer. No comparably validated surrogate end points exist in advanced prostate cancer. METHODS: We searched for trials in advanced prostate cancer, defined as node-positive, metastatic castration-sensitive, nonmetastatic, or metastatic castration-resistant prostate cancer. Eligible randomized trials reported OS and one or more intermediate clinical end points, including biochemical failure (BF), clinical failure, biochemical failure–free survival (BFS), progression-free survival (PFS), and radiographic PFS. Candidacy for surrogacy was assessed by using the second condition of the meta-analytic approach; R2 was weighted by the inverse variance of the log intermediate clinical end point hazard ratio and defined as R2>0.70. RESULTS: A total of 143 randomized trials (n=75,601 patients) were included. No candidate end points met the criteria for surrogacy (R2 BF [n=28,922], 0.42 [95% confidence interval (CI), 0.18 to 0.64]; BFS [n=25,741], 0.57 [95% CI, 0.37 to 0.73]; clinical failure [n=22,616], 0.31 [95% CI, 0.075 to 0.56]; PFS [n=52,639], 0.50 [95% CI, 0.35 to 0.63]; and radiographic PFS [n=52,548], 0.50 [95% CI, 0.35 to 0.63]). Within preplanned subgroups according to castration-sensitive or castration-resistant disease or according to treatment type, neither BFS nor PFS consistently met criteria for surrogacy. Sensitivity analyses showed that candidacy for surrogacy of all end points tested did not change over time. CONCLUSIONS: Our aggregate screening method for surrogate end points in advanced prostate cancer showed that commonly used clinical end points are not clear valid surrogate end points for OS. (Funded by the Prostate Cancer Foundation and the National Cancer Institute.)

Purpose: There remains a lack of clarity regarding the influence of sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) on outcomes in prostate cancer (PCa). Herein, we evaluate the optimal sequencing of ADT with prostate-directed RT in localized PCa., Methods: MEDLINE (1966-2018), Embase (1982-2018), ClinicalTrials.gov, and conference proceedings (1990-2018) were searched to identify randomized trials evaluating the sequencing, but not duration, of ADT with RT. Two randomized phase III trials were identified, and individual patient data were obtained: Ottawa 0101 and NRG Oncology's Radiation Therapy Oncology Group 9413. Ottawa 0101 randomly assigned patients to neoadjuvant or concurrent versus concurrent or adjuvant short-term ADT. Radiation Therapy Oncology Group 9413, a 2 × 2 factorial trial, included a random assignment of neoadjuvant or concurrent versus adjuvant short-term ADT. The neoadjuvant or concurrent ADT arms of both trials were combined into the neoadjuvant group, and the arms receiving adjuvant ADT were combined into the adjuvant group. The primary end point of this meta-analysis was progression-free survival (PFS)., Results: The median follow-up was 14.9 years. Overall, 1,065 patients were included (531 neoadjuvant and 534 adjuvant). PFS was significantly improved in the adjuvant group (15-year PFS, 29% v 36%, hazard ratio [HR], 1.25 [95% CI, 1.07 to 1.47], P = .01). Biochemical failure (subdistribution HR [sHR], 1.37 [95% CI, 1.12 to 1.68], P = .002), distant metastasis (sHR, 1.40 [95% CI, 1.00 to 1.95], P = .04), and metastasis-free survival (HR, 1.17 [95% CI, 1.00 to 1.37], P = .050) were all significantly improved in the adjuvant group. There were no differences in late grade ≥ 3 gastrointestinal (2% v 3%, P = .33) or genitourinary toxicity (5% v 5%, P = .76) between groups., Conclusion: The sequencing of ADT with prostate-directed RT has significant association with long-term PFS and MFS in localized PCa. Our findings favor use of an adjuvant over a neoadjuvant approach, without any increase in long-term toxicity.

Purpose: In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT., Materials and Methods: A systematic review identified published randomized trials comparing EBRT with or without ADT, or EBRT (with or without ADT) with or without BT, that reported on overall survival (OS). Standard fixed-effects meta-analyses were performed for each comparison, and a meta-regression was conducted to adjust for use and duration of ADT. Network meta-analyses were performed to compare EBRT plus ADT versus EBRT plus BT. Bayesian analyses were also performed, and a rank was assigned to each treatment after Markov Chain Monte Carlo analyses to create a surface under the cumulative ranking curve., Results: Six trials compared EBRT with or without ADT (n = 4,663), and 3 compared EBRT with or without BT (n = 718). The addition of ADT to EBRT improved OS (hazard ratio [HR], 0.71 [95% CI, 0.62 to 0.81]), whereas the addition of BT did not significantly improve OS (HR, 1.03 [95% CI, 0.78 to 1.36]). In a network meta-analysis, EBRT plus ADT had improved OS compared with EBRT plus BT (HR, 0.68 [95% CI, 0.52 to 0.89]). Bayesian modeling demonstrated an 88% probability that EBRT plus ADT resulted in superior OS compared with EBRT plus BT., Conclusion: Our findings suggest that current practice patterns of omitting ADT with EBRT plus BT may result in inferior OS compared with EBRT plus ADT in men with intermediate- and high-risk prostate cancer. ADT for these men should remain a critical component of treatment regardless of radiotherapy delivery method until randomized evidence demonstrates otherwise.

Randomized clinical trials assessing novel therapies in men with localized prostate cancer frequently require large patient numbers and more than a decade of follow-up to demonstrate improvements in overall survival. As the landscape of treatment options for prostate cancer is rapidly changing, clinical trials requiring long follow-up threaten to impede treatment improvements and run the risk of results being obsolete by the time that they are reported in publication. To address these issues, there has been tremendous interest in identifying an intermediate clinical endpoint that can be assessed earlier in the disease course to serve as a robust surrogate for overall survival in men with localized prostate cancer. Herein we review the relevant data for surrogate endpoints in localized prostate cancer, highlighting the work performed by the Intermediate Clinical Endpoints in Cancer of the Prostate Working Group identifying metastasis-free survival as a valid surrogate for men treated for localized prostate cancer.

Purpose: Utilization of stereotactic body radiation therapy (SBRT) for treatment of localized prostate cancer is increasing. Guidelines and payers variably support the use of prostate SBRT. We therefore sought to systematically analyze biochemical recurrence-free survival (bRFS), physician-reported toxicity, and patient-reported outcomes after prostate SBRT., Methods and Materials: A systematic search leveraging Medline via PubMed and EMBASE for original articles published between January 1990 and January 2018 was performed. This was supplemented by abstracts with sufficient extractable data from January 2013 to March 2018. All prospective series assessing curative-intent prostate SBRT for localized prostate cancer reporting bRFS, physician-reported toxicity, and patient-reported quality of life with a minimum of 1-year follow-up were included. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Meta-analyses were performed with random-effect modeling. Extent of heterogeneity between studies was determined by the I 2 and Cochran's Q tests. Meta-regression was performed using Hartung-Knapp methods., Results: Thirty-eight unique prospective series were identified comprising 6116 patients. Median follow-up was 39 months across all patients (range, 12-115 months). Ninety-two percent, 78%, and 38% of studies included low, intermediate, and high-risk patients. Overall, 5- and 7-year bRFS rates were 95.3% (95% confidence interval [CI], 91.3%-97.5%) and 93.7% (95% CI, 91.4%-95.5%), respectively. Estimated late grade ≥3 genitourinary and gastrointestinal toxicity rates were 2.0% (95% CI, 1.4%-2.8%) and 1.1% (95% CI, 0.6%-2.0%), respectively. By 2 years post-SBRT, Expanded Prostate Cancer Index Composite urinary and bowel domain scores returned to baseline. Increasing dose of SBRT was associated with improved biochemical control (P = .018) but worse late grade ≥3 GU toxicity (P = .014)., Conclusions: Prostate SBRT has substantial prospective evidence supporting its use, with favorable tumor control, patient-reported quality of life, and levels of toxicity demonstrated. SBRT has sufficient evidence to be supported as a standard treatment option for localized prostate cancer while ongoing trials assess its potential superiority., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: Black men are more likely to die of prostate cancer than white men. In men with similar stages of disease, the contribution of biological vs nonbiological differences to this observed disparity is unclear., Objective: To quantify the association of black race with long-term survival outcomes after controlling for known prognostic variables and access to care among men with prostate cancer., Design, Setting, and Participants: This multiple-cohort study included updated individual patient-level data of men with clinical T1-4N0-1M0 prostate cancer from the following 3 cohorts: Surveillance, Epidemiology, and End Results (SEER [n = 296 273]); 5 equal-access regional medical centers within the Veterans Affairs health system (VA [n = 3972]); and 4 pooled National Cancer Institute-sponsored Radiation Therapy Oncology Group phase 3 randomized clinical trials (RCTs [n = 5854]). Data were collected in the 3 cohorts from January 1, 1992, through December 31, 2013, and analyzed from April 27, 2017, through April 13, 2019., Exposures: In the VA and RCT cohorts, all patients received surgery and radiotherapy, respectively, with curative intent. In SEER, radical treatment, hormone therapy, or conservative management were received., Main Outcomes and Measures: Prostate cancer-specific mortality (PCSM). Secondary measures included other-cause mortality (OCM). To adjust for demographic-, cancer-, and treatment-related baseline differences, inverse probability weighting (IPW) was performed., Results: Among the 306 100 participants included in the analysis (mean [SD] age, 64.9 [8.9] years), black men constituted 52 840 patients (17.8%) in the SEER cohort, 1513 (38.1%) in the VA cohort, and 1129 (19.3%) in the RCT cohort. Black race was associated with an increased age-adjusted PCSM hazard (subdistribution hazard ratio [sHR], 1.30; 95% CI, 1.23-1.37; P < .001) within the SEER cohort. After IPW adjustment, black race was associated with a 0.5% (95% CI, 0.2%-0.9%) increase in PCSM at 10 years after diagnosis (sHR, 1.09; 95% CI, 1.04-1.15; P < .001), with no significant difference for high-risk men (sHR, 1.04; 95% CI, 0.97-1.12; P = .29). No significant differences in PCSM were found in the VA IPW cohort (sHR, 0.85; 95% CI, 0.56-1.30; P = .46), and black men had a significantly lower hazard in the RCT IPW cohort (sHR, 0.81; 95% CI, 0.66-0.99; P = .04). Black men had a significantly increased hazard of OCM in the SEER (sHR, 1.30; 95% CI, 1.27-1.34; P < .001) and RCT (sHR, 1.17; 95% CI, 1.06-1.29; P = .002) IPW cohorts., Conclusions and Relevance: In this study, after adjustment for nonbiological differences, notably access to care and standardized treatment, black race did not appear to be associated with inferior stage-for-stage PCSM. A large disparity remained in OCM for black men with nonmetastatic prostate cancer.

Objective: To elucidate the functional erection rate after prostate stereotactic body radiotherapy (SBRT) and to develop a comprehensive prognostic model of outcomes after treatment., Patients and Methods: Between 2008 and 2013, 373 consecutive men with localized prostate cancer were treated with SBRT at a single academic institution as part of a prospective clinical trial or prospective registry. Prospective longitudinal patient-reported health-related quality of life (HRQoL) data was collected using the Expanded Prostate Cancer Index Composite (EPIC)-26 instrument. Functional erections were strictly defined as 'firm enough for intercourse' according to EPIC-26. Detailed comorbidity data were also collected. Logistic regression models were used to predict 24- and 60-month functional erection rates. Observed erection rates after SBRT were compared with those after other radiation therapies (external beam radiation therapy [EBRT] and brachytherapy) using prospectively validated models., Results: The median (interquartile range) follow-up was 56 (37-73) months and the response rate at 2 years was 84%. For those with functional erections at baseline, 57% and 45% retained function at 24 and 60 months, respectively. On multivariable analysis for 24-month erectile function, significant variables included higher baseline sexual HRQoL (adjusted odds ratio [aOR] 1.55 per 10 points, 95% confidence interval [CI] 1.37-1.74; P < 0.001) and older age (aOR 0.66 per 10 years, 95% CI 0.43-1.00; P = 0.05). At 60 months, baseline HRQoL and age remained associated with erectile function, along with body mass index (aOR 0.45, 95% CI 0.26-0.78; P < 0.001). The 24- and 60-month models had excellent discrimination (c-index 0.81 and 0.84, respectively). Erection rates after SBRT were not statistically different from model-predicted rates after EBRT or brachytherapy for the whole cohort and the cohort with baseline erectile function., Conclusions: Intermediate- to long-term post-SBRT erectile function results are promising and not significantly different from other radiotherapy techniques. Clinicians can use our prognostic model to counsel patients regarding expected erectile function after SBRT., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)