PURPOSE:This study investigates a short-course, intensified regimen combining apalutamide, abiraterone acetate, and prednisone (AAP) and stereotactic body radiotherapy (SBRT) to reduce treatment burden and improve disease control in a very high-risk (VHR) population inadequately represented in prior trials. PATIENTS AND METHODS:This multi-institutional, single-arm, phase 2 trial enrolled patients with VHR localized prostate cancer, defined according to the National Comprehensive Cancer Network as histologically confirmed adenocarcinoma with ≥2 high-risk features: Gleason score 8 to 10, prostate-specific antigen (PSA) ≥20, clinical or radiographic ≥T3, or >4 cores containing Gleason score 8 disease. Patients received 6 months of apalutamide, abiraterone acetate, and leuprolide plus prostate/seminal vesicle-directed ultra-fractionated SBRT. The primary endpoint was 3-year biochemical recurrence (BCR) rate by Phoenix criteria, with a prespecified superiority threshold of <10%. Secondary endpoints included PSA ≥0.2 ng/mL, metastasis-free survival (MFS), and time to testosterone recovery >150 ng/dL. RESULTS:Between August 2016 and December 2022, 63 patients were treated. At 3 years, the Phoenix-defined BCR rate was 19%. BCR-free survival was 84.2% [95% confidence interval (CI), 75.6-93.7] with a median follow-up of 41 months (34-43). The 3-year MFS was 93.6% (95% CI, 87.8%-99.8%), with no deaths observed. The median time to testosterone recovery >150 ng/dL was 6 months (range, 3-24 months). No new safety signals emerged, and the only significant quality-of-life (QOL) decline was in the EPIC sexual subdomain at 12 months. CONCLUSIONS:Treatment intensification with apalutamide, AAP, androgen deprivation therapy, and SBRT was well-tolerated with limited impact on QOL. Although BCR rates exceed the superiority threshold, outcomes aligned with historic benchmarks, supporting further evaluation of the regimen in prospective trials.

BACKGROUND:For over a decade the Advanced Prostate Cancer Consensus Conference (APCCC) covers a variety of topics that greatly impact daily practice. In 2025, a dedicated event was organised to discuss key questions in clinical management of patients with prostate cancer (PC) related to diagnostic tools (APCCC Diagnostics). Here we present the voting results of the APCCC Diagnostics questions. OBJECTIVE; DESIGN, SETTING, AND PARTECIPANTS: APCCC Diagnostics 2025 is a pilot project. The scientific committee for APCCC Diagnostics 2025 developed 88 multiple-choice consensus questions on six different topics. Prior to the conference, the panel members (''panellists'') voted on these questions via a web-based survey. Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS:Consensus was only reached on 17 of 88 questions (19%), of which six (7%) received a strong consensus. Specifically, consensus was reached for two of 17 questions (14%) in "how to diagnose PC"; seven of 16 (44%) in "how to stage PC"; three of 14 (21%) in "Biochemical Recurrence Scenario"; two of 11 (18%) in "metastatic disease: what to do?"; zero of 18 (0%) in "monitoring metastatic PC"; and three of 12 (25%) in "radioligand therapy and imaging." CONCLUSIONS:The voting results and their discussion may assist physicians in navigating controversial areas of clinical management related to diagnosis, staging, and restaging in the different clinical settings for PC, particularly where high-level evidence is scarce or conflicting. The findings can also help funders and policymakers in prioritising areas for future research.

BACKGROUND AND OBJECTIVE:Trimodality therapy (TMT) is an accepted bladder-preserving option for selected patients with muscle-invasive bladder cancer (MIBC). Pembrolizumab has demonstrated activity in MIBC and may enhance the effects of chemotherapy and radiation. We evaluated the safety and efficacy of adding pembrolizumab to TMT. METHODS:In this multicenter phase 2 trial, patients with MIBC received one dose of pembrolizumab followed by maximal transurethral resection, then definitive bladder radiation with concurrent low-dose gemcitabine and pembrolizumab every 3 wk for three doses. The primary end point was 2-yr bladder-intact disease-free survival (BIDFS). Secondary end points included safety, metastasis-free survival (MFS), and overall survival (OS). KEY FINDINGS AND LIMITATIONS:Fifty-four patients were enrolled, including 48 in the efficacy cohort; 67% had clinical stage T2 disease. The 2-yr BIDFS was 60% (95% confidence interval [CI], 45-73). Two-yr MFS and OS were 81% (95% CI, 66-92) and 83% (95% CI, 69-91), respectively. Grade ≥3 treatment-related adverse events occurred in 25% of patients. Limitations include the single-arm design and modest sample size. CONCLUSIONS AND CLINICAL IMPLICATIONS:Pembrolizumab combined with gemcitabine-based chemoradiation was feasible and showed efficacy comparable to standard TMT. Ongoing phase 3 trials will further define its role in bladder preservation.

The NCCN Guidelines for Prostate Cancer include recommendations for staging and risk assessment after a prostate cancer diagnosis and for the care of patients with localized, regional, recurrent, and metastatic disease. These NCCN Guidelines Insights summarize the panel's discussions on select 2026 updates to the guidelines regarding nonmetastatic disease: the elimination of the very-low-risk group, updates to the Principles of Active Surveillance, and caution in the use of focal therapy in newly diagnosed patients.

PURPOSE:The association between late toxicity and biochemical recurrence (BCR) after prostate radiation therapy is unclear. We set out to characterize the relationship between late gastrointestinal (GI) and genitourinary (GU) toxicity and BCR among patients receiving conventionally fractionated (CF) or moderately hypofractionated (MHF) prostate radiation therapy. METHODS AND MATERIALS:This was an individual patient data meta-analysis that identified randomized phase 3 trials of CF or MHF prostate radiation therapy in the MARCAP (Meta-Analysis of Randomized trials in Cancer of the Prostate) Consortium that had individual-level late toxicity and BCR data available. Data were provided to MARCAP by study investigators. The associations between BCR and late (>3 months after radiation therapy) grade ≥2 GI and GU toxicities were assessed using Fine-Gray subdistribution hazard models with an 18-month landmark to address immortal time bias. RESULTS:Seven of 26 available trials met all eligibility criteria. A total of 6761 patients were included (CF: n = 4333; MHF: n = 2428). Median follow-up was 72 months (IQR, 61-94 months). BCR occurred in 17.0% of patients (1142/6732). The rate of late grade ≥2 GI toxicity was 14.3% (965/6761), although the rate of grade ≥2 GU toxicity was 15.5% (1045/6761). BCR was inversely associated with late grade ≥2 GI toxicity (subdistribution hazard ratio, 0.64; 95% CI, 0.43-0.96; P = .03). BCR was not significantly associated with late grade ≥2 GU toxicity (subdistribution hazard ratio, 1.06; 95% CI, 0.70-1.60; P = .78). CONCLUSIONS:Late grade ≥2 GI toxicity was significantly associated with lower rates of BCR. We hypothesize that this may be related to the impact of prostatic motion during treatment, specifically anterosuperior motion of the prostate that would increase the dose to the rectum and to posterior dominant intraprostatic lesions. Late grade ≥2 GU toxicity did not appear to be associated with BCR.

PURPOSE:Precision medicine has revolutionized oncology; however, tumor biomarkers are not reflective of the heterogeneous cancer population. We evaluated NRG Oncology prostate cancer (PCa) clinical trials for demographic differences among patients with optional biospecimen collection (BC) consent and biospecimen submission (BSub). METHODS:Data from 19 NRG PCa clinical trials closed before 2015 were analyzed. Patients who consented to BC and completed BSub were evaluated by race, ethnicity, median income, area deprivation index (ADI; categorized as highest v lowest three quartiles), age at enrollment, site, and year of enrollment. T/chi-square tests were used for continuous/categorical variables, respectively, followed by logistic regression. RESULTS:Of the 15,648 randomized patients eligible for BC, 11,796 (75%) had specimens submitted. In all, 4,598 (82.2%) of 5,597 eligible patients consented for optional BC in nine clinical trials with a separate BC consent process (consent rates by race/ethnicity: 74.1% Black, 72.8% Hispanic/Latino, 83.8% White). A smaller proportion of Black and Hispanic/Latino patients consented to optional BC compared with those who did not (12.1% v 19.5% Black, P < .0001; 3.5% v 5.8% Hispanic, P = .0006). In univariable logistic regression models, high ADI (more socioeconomic disadvantage) was associated with a decreased likelihood for optional BC consent (odds ratio [OR], 0.67 [95% CI, 0.55 to 0.82]; P = .02), but not a decreased likelihood for BSub (OR, 0.74 [95% CI, 0.53 to 1.04]; P = .08). Multivariable models demonstrated that Black/Hispanic/Latino patients were less likely to consent to optional BC, and Black patients were less likely to have BSub (P < .05 for all). CONCLUSION:White/non-Hispanic patients and those with less socioeconomic disadvantage were more likely to consent to optional BC, whereas Black patients were less likely to have BSub. Targeted solutions are needed to improve biorepository representation so that precision medicine approaches better reflect the cancer population.

BACKGROUND:Issues with randomized controlled trial generalizability are well described, but whether these issues result from differences in patient treatment across contexts remains unknown. We studied treatment of patients with high-risk prostate cancer after radical prostatectomy inside and outside a randomized controlled trial evaluating the impact of a genomic classifier on post-radical prostatectomy treatment decision making (Genomics in Michigan Impacting Observation of Radiation [G-MINOR]; ClinicalTrials.gov identifier NCT02783950). METHODS:G-MINOR enrolled 338 patients; propensity score-matched eligible but unenrolled patient cohorts (pretrial and trial contemporary) from the Michigan Urological Surgery Improvement Collaborative (MUSIC), in which the trial was embedded, were compared for rates and time to secondary treatment (adjuvant or salvage therapy) after prostatectomy. RESULTS:Among 338 patients in the G-MINOR cohort, 69 (31 adjuvant, 38 salvage) received secondary treatment compared with 266 (183 adjuvant, 83 salvage) and 104 (60 adjuvant, 44 salvage) in the 1014 contemporary and 338 pretrial-matched MUSIC cohorts. Time to secondary treatment was much shorter in the MUSIC cohort across all comparisons. For example, matching G-MINOR to synchronous MUSIC patients demonstrated 84% vs 74% estimated 2-year treatment-free survival for trial and real-world patients, respectively (P < .001). CONCLUSIONS:Controlling for key clinicopathologic factors, patients in the G-MINOR randomized controlled trial and MUSIC cohorts were treated differently, even after stratifying by genomic risk. These findings suggest that challenges in randomized controlled trial generalizability extend beyond the representativeness of trial participants. Differences in management may also explain why divergent patient outcomes are observed in randomized controlled trials vs real-world settings.

PURPOSE:Although outcomes for nonmetastatic cancers have improved since the 1970s, it remains uncertain whether long-term survival has improved among patients presenting with de novo metastatic disease, defined as cancer presenting with distant metastases at the time of initial diagnosis. This study evaluated changes in 5-year survival among patients with de novo metastatic cancer diagnosed in 1976 versus 2015, with a minimum 5-year follow-up through 1981 and 2020, respectively. METHODS:Population-based data were obtained from the SEER database. Patients diagnosed with de novo metastatic cancer in 1976 (n = 11,864) and 2015 (n = 26,324) were included. Five-year overall survival (OS) was compared between cohorts, and multivariable logistic regression identified demographic and clinical factors associated with survival. RESULTS:The 5-year OS increased significantly from 10.6% in 1976-1981 to 23.6% in 2015-2020 (P < .001). Survival gains were largest in breast cancer (12.6%-34.2%; P < .001), ovarian cancer (14.4%-32.5%; P < .001), colorectal cancer (3.7%-15.0%; P < .001), and hematologic malignancies (24.3%-53.9%; P < .001). Minimal improvement occurred in pancreatic cancer (0.25%-1.6%; P = .007) and small cell lung cancer (0.8%-3.1%; P = .008). Multivariable analysis demonstrated that older age, male sex, and Black race were associated with lower odds of 5-year survival (all P < .01). CONCLUSION:Over the past four decades, long-term survival among patients with de novo metastatic cancer has more than doubled; however, progress remains uneven across cancer types. Gains appear concentrated in malignancies with substantial therapeutic advances, whereas others show persistently poor outcomes. Continued efforts are needed to address disparities and improve survival in resistant cancer types.

BACKGROUND:Clinical studies have shown that outcomes of patients with prostate cancer could vary depending on race. In this study, the authors sought to determine if the treatment effect of apalutamide, an androgen receptor pathway inhibitor (ARPI), on overall survival (OS) varies depending on the race of the patient. METHODS:This pooled analysis includes individual patient data from two phase 3 trials, TITAN and SPARTAN, which randomized patients to androgen deprivation therapy (ADT) ± apalutamide in metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer, respectively. Race was self-identified and categorized as Asian, Black, White, and Others categories. The authors applied a stratified (stratification for the trial) multivariable Cox proportional hazards regression model to determine heterogeneity of treatment effect on OS after adjustment for age, performance status, body mass index, T- and N-stage, Gleason score, comorbidities, and exposure to statins and metformin. RESULTS:Overall, 2190 patients were included: 16.9% patients were Asian, 3.7% were Black, 67.4% were White, and 12.0% were from the Others category. The authors did not find any significant heterogeneity of treatment effect from apalutamide on OS across racial groups (interaction-p = .46). Among ADT plus apalutamide-treated patients, there was no association of race with OS (hazard ratio for Asian, 0.77 [95% CI, 0.56-1.06]; Black, 0.82 [95% CI, 0.49-1.37]; and Others, 1.00 [95% CI, 0.75-1.34], all compared to White). CONCLUSIONS:In this study, the authors did not find any evidence of difference in the treatment effect of apalutamide on OS across patients of different races, although interpretation remains limited by poor representation of racial minorities. Among apalutamide-treated patients, there was no association of race with OS.

Background:Cancer progression is often accompanied by dedifferentiation and acquisition of stem cell-like properties (stemness). In prostate cancer (PCa), lineage plasticity and therapy resistance remain major clinical challenges, yet a unified quantitative transcriptomic framework connecting stemness, androgen receptor (AR) signaling, castration resistance, and disease progression across the PCa continuum is lacking. Methods:We integrated 87,339 transcriptomic profiles from 33 preclinical and clinical datasets spanning the PCa continuum from normal prostate and treatment-naïve primary PCa (Pri-PCa) to PCa treated with neoadjuvant ADT (nADT) and metastatic castration-resistant PCa (mCRPC), with single-cell RNA-seq analyses encompassing 115,197 cells. Cancer stemness was quantified using a transcriptome-derived mRNA-based Stemness Index (mRNAsi; hereafter Stemness), and a 12-gene PCa-Stem signature was developed to capture PCa-specific stemness. Stemness, PCa-Stem, canonical AR activity (c_AR-A), castration-reprogrammed AR activity (cr_AR-A), RB1 -loss, PTEN -loss, and MYC activity signatures were quantified across cohorts. Functional validation included MYC inhibition and representative PCa-Stem signature gene depletion in PCa models. Clinical prognostic significance was evaluated in independent patient cohorts. Results:The Stemness score and c_AR-A increased concordantly during early prostate tumorigenesis but diverged with PCa progression: as Gleason grade increased, c_AR-A declined while Stemness continually increased. mCRPC exhibited the highest Stemness and lowest c_AR-A, a pattern recapitulated in Pten / Rb1 / Trp53 -deficient mouse models. Global Stemness increased progressively across the PCa continuum, was enriched in aggressive PAM50-LumB and PCS1 subtypes, associated with proliferative and lineage plasticity programs, and predicted poor patient survival. The newly derived 12-gene PCa-Stem signature provided a PCa-specific molecular representation of Stemness and tracked disease progression and poor patient survival. Network analyses identified a coordinated mitotic regulatory program linking MYC activity, RB1 -loss, cr_AR-A, and the PCa-Stem signature. Spatial and single-cell transcriptomic analyses localized the PCa-Stem program to lineage plasticity-related epithelial cells and demonstrated progressive expansion of PCa-Stem⁺ epithelial cells during PCa progression. Functional perturbation of representative PCa-Stem signature genes, as well as genetic and pharmacological MYC inhibition, consistently suppressed Stemness-associated phenotypes in diverse PCa models. Conclusions:Cancer Stemness quantitatively captures PCa aggressiveness, lineage plasticity, treatment resistance, disease progression, and poor patient survival. cr_AR-A, RB1 loss, and MYC activation cooperate to reinforce the high-Stemness state and therapy resistance in mCRPC. Collectively, our work establishes a trajectory-integrated transcriptomic framework defining cancer Stemness as a quantifiable molecular and clinical determinant of PCa aggressiveness, lineage plasticity, disease progression, therapy resistance and patient survival.

BACKGROUND AND OBJECTIVE:A recent individual patient data (IPD) meta-analysis of randomized trials found a limited overall survival (OS) and metastasis-free survival (MFS) benefit to the addition of hormonal therapy (HT) to postoperative radiotherapy for prostate cancer in patients with pre-radiotherapy prostate-specific antigen (PSA) ≤0.5 ng/ml. We evaluated whether the OS and MFS benefits of adding HT might be significantly modified by an increasing count of adverse pathological features (adverse feature count [AFC]). METHODS:We obtained IPD from five randomized phase 3 trials of postoperative radiotherapy ± HT. AFC was prospectively defined as the sum (0-4) of grade group 4-5 disease, seminal vesicle invasion, positive surgical margins, and extracapsular extension. Intention-to-treat one-stage meta-analytical models were used. We also evaluated the interaction of the benefit of HT with a restricted score comprising only GG4-5 and seminal vesicle invasion (range 0-2), as a pre-specified sensitivity analysis. KEY FINDINGS AND LIMITATIONS:We included IPD from 4781 patients with a median follow-up of 9.1 yr. AFC was independently prognostic for OS and MFS. However, AFC did not significantly modify the OS benefit of HT (interaction hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.79-1.10; p = 0.4) or MFS benefit (interaction HR, 0.88; 95% CI, 0.77-1.01; p = 0.08). Results were similar when AFC was analyzed categorically and in high-risk subsets, and when the restricted AFC score was used. CONCLUSIONS AND CLINICAL IMPLICATIONS:Overall, the data suggest that although adverse pathological features are prognostic, they do not appear predictive of HT benefit after postoperative radiotherapy, which is relevant for patients with a PSA ≤0.5 ng/ml before radiation.

Representativeness of Study Participants

Importance:The treatment of prostate cancer with radiotherapy is evolving. How quickly radiotherapy can be delivered, and the relative risks and benefits of such a treatment, is of significant public interest. Objective:To determine whether stereotactic body radiotherapy (SBRT) was superior to moderately hypofractionated intensity-modulated radiation therapy (MH-IMRT) in terms of patient-reported urinary irritative/obstructive and bowel quality of life and disease-free survival (DFS). Design, Setting, and Participants:NRG-GU005 was a phase-3, international, open-label, randomized clinical trial. The study was activated on November 16, 2017, and closed to accrual on June 8, 2022. Date of last follow-up was October 13, 2024. There were 136 centers in Asia, Canada, Europe, and the United States that accrued patients to the study. Patients with localized prostate cancer, clinical stage T1-T2b with Gleason 3 + 4 (grade group 2) and prostate-specific antigen (PSA) level less than 20 ng/mL or Gleason 3 + 3 (grade group 1) and PSA level 10 to 20 ng/mL were eligible. Intended accrual of 692 patients provided reductions of 8% and 10% in minimal clinically important decline (MCID) frequency for urinary-irritative/obstructive and bowel domains of the Expanded Prostate Cancer Index Composite-26 Item (EPIC-26) instrument at 2 years and greater than 80% power to detect a hazard ratio of 0.62 in DFS. Interventions:Patients were randomized 1:1 to receive SBRT (36.25 Gy in 5 fractions; n = 353) or MH-IMRT (70 Gy in 28 fractions or 60 Gy in 20 fractions; n  =345). Main Outcomes and Measures:Primary outcomes were the frequency of an MCID in the urinary irritative/obstructive and bowel domains of the EPIC-26 at 2 years and DFS at 3 years. Results:A total of 698 patients were randomized. Median age was 68 years; 3% were Asian, 13% Black, and 80% White. Median follow-up was 3.2 years (range, 0-6.5). At 2 years, there was no significant difference in the urinary-irritative domain (35.4% vs 33.7%, P = .68). Urinary incontinence at 1 and 2 years after treatment and sexual function at 1 year after treatment favored SBRT. Fewer grade 3 + 4 genitourinary adverse events occurred in the SBRT vs MH-IMRT group (0.6% vs 2.5%, P = .04). There were significantly fewer MCIDs with SBRT vs MH-IMRT in the bowel domain (34.9% vs 43.8%, P = .03). At 3 years, DFS for MH-IMRT was 92.1% (95% CI, 88.9%-95.2%) vs 88.6% for SBRT (95% CI, 85.2%-92.1%) (1-sided log-rank P < .001). Conclusions and Relevance:Stereotactic body radiotherapy using a modest dose prescription improved multiple quality-of-life domains but was not superior to MH-IMRT in terms of DFS. The rate of PSA failure was not significantly improved in the SBRT vs MH-IMRT group. Trial Registration:ClinicalTrials.gov Identifier: NCT03367702.

PURPOSE:Stereotactic Body Radiation Therapy (SBRT) schedules for prostate cancer are emerging as a standard treatment approach. However, although high efficacy is achieved in clinical trials, additional efforts at accurate treatment delivery are necessary to maximize the therapeutic ratio in the community setting. Kilovoltage Intrafraction Monitoring (KIM) is a technology developed to address the unmet clinical need of accurate intrafraction motion management without a requirement for additional hardware on standard linear accelerators. This paper describes the journey from bench to bedside of KIM. METHODS AND MATERIALS:The concept of KIM emerged in 2008 in a series of simulations, progressing to phantom experiments commencing in 2010, culminating in the first clinical trial starting in 2014. A series of technical innovations integrating rotational prostate movements, quality assurance, and dynamic multileaf collimator tracking were included within the multi-institutional Trans-Tasman Radiation Oncology Group 15.01 Stereotactic Prostate Adaptive Radiation therapy using KIM clinical trial for prostate SBRT. RESULTS:Submillimeter accuracy of KIM was observed in simulations, phantom experiments, and clinical trials. The Stereotactic Prostate Adaptive Radiation therapy using KIM trial demonstrated multicenter feasibility of use, a high rate of intrafraction motion triggering a gating event, and a significant dosimetric impact of KIM deployment for target volume coverage. KIM is being made available through commercialization with an industry partner, and through a 300-patient, 10-center clinical trial. CONCLUSIONS:The collaboration between researchers, clinicians, and industry has led to KIM being developed from a concept to clinical trials, enabling the safe delivery of prostate cancer SBRT in the presence of intrafraction motion. This journey provides a template for similar bench-to-bedside translational research.

PURPOSE:Recently, results from National Surgical Adjuvant Breast and Bowel Project; Radiation Therapy Oncology Group; Gynecologic Oncologic Group (NRG/RTOG) 0924, the largest randomized trial to evaluate the benefit of whole-pelvic radiation therapy (WPRT) in localized prostate cancer, were presented. We conducted an aggregate meta-analysis of all phase III randomized trials to determine the impact of WPRT on oncologic outcomes. METHODS:PubMed via MEDLINE, clinicaltrials.gov, and conference proceedings were systematically searched for randomized trials of ±WPRT in localized prostate cancer conducted between 1980 and 2025. Random-effects models were used to generate pooled hazard ratios (HRs) with 95% CIs. Heterogeneity was assessed with I2 statistics, and leave-one-out sensitivity analyses were performed. Meta-regression was performed to assess the influence of the proportion of patients with Gleason score 7 to 10, use of androgen deprivation therapy, radiation therapy dose, and field size. Endpoints assessed included overall survival, a biochemical-based endpoint, referred to as biochemical recurrence, and distant metastasis. RESULTS:Four randomized trials were identified (n = 4465 patients), including 3 multicenter cooperative group trials Urogenital Tumor Study Group-French Association of Urology (GETUG-AFU-01, RTOG 9413, and RTOG 0924) and 1 single-institution trial Prostate-Only versus Whole-Pelvic Radiation Therapy (POP-RT). WPRT did not improve overall survival (HR, 1.05; 95% CI, 0.95-1.16; I2 = 0%), biochemical recurrence (HR, 0.82; 95% CI, 0.63-1.07; I2 = 76%), or distant metastasis (HR, 0.88; 95% CI, 0.58-1.34; I2 = 68%). The high rates of heterogeneity observed were due primarily to the POP-RT trial. In sensitivity analyses, excluding POP-RT heterogeneity was eliminated (HR for biochemical recurrence was 0.91 [95% CI, 0.81-1.02; I2 = 0%]; HR for distant metastasis was 1.06 [95% CI, 0.87-1.29; I2 = 0%]). Meta-regression found no significant modifying effect of any covariables assessed. CONCLUSIONS:This aggregate meta-analysis did not demonstrate any meaningful benefit of WPRT over prostate-only radiation therapy in unselected localized prostate cancer. Individual patient data meta-analysis is warranted to understand whether any subgroup consistently derives benefit from WPRT.