2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/2iy5wruuedsh6.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/00yc7rcvua6a7.js","/_next/static/immutable/chunks/37ktb71aq3480.js","/_next/static/immutable/chunks/2d50b-7eu4558.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/2d6noqpp6ehas.js","/_next/static/immutable/chunks/1sx186c93bpzg.js","/_next/static/immutable/chunks/3dc-1n866s65i.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2w1bvggzb0ga8.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T780,The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer. We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer. PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)-defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator-naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.31:T9c9, PURPOSE The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer. METHODS We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer. RESULTS PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)–defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. CONCLUSION PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator–naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Erleada: brand Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Erleada (brand). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/brand/Erleada\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Brands\",\"item\":\"https://www.reachrx.ai/hub/tag/brand\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"Erleada\",\"item\":\"https://www.reachrx.ai/hub/tag/brand/Erleada\"}]}}"}}]],["$","$L2f",null,{"title":"Erleada: Research & Clinical Takeaways","description":"See clinical studies on Erleada — efficacy, safety signals, dosing, and head-to-head results.","papers":[{"doi":"10.1002/cncr.70494","pmid":"42572469","title":"How low do you need to go? Association between various prostate‐specific antigen response measures and clinical outcomes in metastatic castration‐sensitive prostate cancer in the Veterans Health Administration data","journal_title":"Cancer","journal_issn":"0008-543X","published_at":"2026-08-10T00:00:00.000Z","url":"https://pubmed.ncbi.nlm.nih.gov/42572469/","source_score":55,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-17T13:33:07.267Z","updated_at":"2026-08-17T13:33:07.267Z","tags":[{"paper_doi":"10.1002/cncr.70494","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"brand","value":"Erleada","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"brand","value":"Nubeqa","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"brand","value":"Xtandi","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"brand","value":"Zytiga","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"condition","value":"Metastatic Castration-Sensitive Prostate Cancer","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"generic","value":"abiraterone","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"generic","value":"apalutamide","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"generic","value":"darolutamide","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"generic","value":"docetaxel","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"generic","value":"enzalutamide","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"modality","value":"Androgen Deprivation Therapy","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"modality","value":"Androgen Receptor Pathway Inhibitor","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"sample_size","value":"n=4890","value_numeric":4890},{"paper_doi":"10.1002/cncr.70494","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"warning","value":"Generalizability is limited: the VHA population is predominantly older, male, and includes a high proportion of Black patients (29%), which may not reflect the broader mCSPC population.","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"warning","value":"Impact flag 'practice_changing' applied because PSA <0.2 ng/mL as the target metric directly contradicts the majority of current real-world physician practice (85% use % decline), though this is a retrospective observational study and causality cannot be established.","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"warning","value":"Plain language summary states data from 2018–2023 for index dates, while the methods section states VHA data from 2006–2024 — the broader date range reflects data availability, with index dates restricted to 2018–2023.","value_numeric":null},{"paper_doi":"10.1002/cncr.70494","tag_type":"warning","value":"Study sponsored by Pfizer and Astellas (codevelopers of enzalutamide); several authors are employees or shareholders of these companies — potential for sponsorship bias.","value_numeric":null}],"summaries":{"what_studied":"This retrospective cohort study used Veterans Health Administration data (2006–2024, index dates 2018–2023) to compare two PSA-response metrics — PSA nadir <0.2 ng/mL vs. ≥90% PSA decline within 9 months of ADT initiation — and their association with overall survival (OS) and disease progression in 4,890 men with mCSPC receiving ADT ± ARPIs, NSAAs, or docetaxel.","key_result":"Achieving PSA <0.2 ng/mL within 9 months was associated with a 54% lower risk of death (adjusted HR 0.46; 95% CI 0.40–0.54) and a 55% lower risk of disease progression (adjusted HR 0.45; 95% CI 0.40–0.50) vs. not achieving it; 3-year OS was ~78–83% vs. ~48–51%. In contrast, ≥90% PSA decline alone (without reaching <0.2 ng/mL) was not associated with improved OS or disease progression. ADT + ARPI nearly doubled the rate of achieving PSA <0.2 ng/mL vs. ADT alone (OR 2.36; 95% CI 1.97–2.83).","limitations":"- Retrospective VHA cohort; findings may not generalize beyond a predominantly older male veteran population.\n- Key confounders (tumor grade, disease volume) were unavailable in the administrative dataset.\n- Testosterone levels were not used to define castration sensitivity, and administrative coding inaccuracies may affect cohort classification.","practice_takeaway":"Clinicians should target a PSA nadir <0.2 ng/mL — not just ≥90% PSA decline — when assessing treatment response in mCSPC, as only the absolute threshold predicts improved survival and delayed progression. Adding an ARPI to ADT more than doubles the odds of reaching this target and should be considered the standard approach."}},{"doi":"10.1056/nejmoa2603878","pmid":"42223077","title":"Perioperative Apalutamide in High-Risk Localized Prostate Cancer","journal_title":"New England Journal of Medicine","journal_issn":"0028-4793","published_at":"2026-05-31T00:00:00.000Z","url":"https://doi.org/10.1056/nejmoa2603878","source_score":367,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-13T15:34:49.030Z","updated_at":"2026-06-13T15:34:49.030Z","tags":[{"paper_doi":"10.1056/nejmoa2603878","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"brand","value":"Erleada","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"condition","value":"Prostate Cancer","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"generic","value":"apalutamide","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"modality","value":"Androgen Deprivation Therapy","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"modality","value":"Androgen Receptor Inhibitor","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"sample_size","value":"n=2109","value_numeric":2109},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"warning","value":"Overall survival data were not reported; long-term survival benefit remains unconfirmed.","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"warning","value":"PSMA-PET was used as an imaging modality for metastasis-free survival assessment, which may affect comparability with older trials that used conventional imaging only.","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"warning","value":"The absolute 5-year metastasis-free survival difference (~4.7%) is statistically significant but modest — clinical significance should be weighed against the higher adverse event burden.","value_numeric":null},{"paper_doi":"10.1056/nejmoa2603878","tag_type":"warning","value":"Trial was funded by Johnson & Johnson (manufacturer of apalutamide); sponsorship bias cannot be excluded.","value_numeric":null}],"summaries":{"practice_takeaway":"For patients with high-risk localized or locally advanced prostate cancer undergoing radical prostatectomy, adding perioperative apalutamide to ADT improves pathological response rates and metastasis-free survival. Clinicians should counsel patients about a meaningfully higher risk of grade 3–4 adverse events, particularly rash (~8–9% higher rate), when considering this regimen.","what_studied":"Phase 3, double-blind, placebo-controlled trial (PROTEUS) evaluating perioperative ADT + apalutamide (240 mg/day) vs. ADT + placebo for 6 cycles (28 days each) before and after radical prostatectomy with pelvic lymph-node dissection in 2,109 patients with newly diagnosed high-risk localized or locally advanced prostate cancer; median follow-up 61.7 months.","key_result":"Pathological complete response or minimal residual disease was significantly higher with apalutamide (8.9% vs. 1.0%; OR 10.17; 95% CI 5.27–19.64; P<0.001). 5-year metastasis-free survival favored apalutamide (78.2% vs. 73.5%; HR 0.80; 95% CI 0.67–0.96; P=0.02). Event-free survival, time to first subsequent treatment, and time to distant metastasis all significantly favored apalutamide (P<0.001 for each). Grade 3–4 adverse events occurred in 39.6% vs. 31.0%, driven primarily by higher rash rates.","limitations":"- Overall survival data are not yet reported; metastasis-free survival benefit (absolute difference ~4.7% at 5 years) is modest.\n- Industry-funded (Johnson & Johnson), introducing potential sponsorship bias.\n- Generalizability may be limited as PSMA-PET staging criteria evolved during the trial period."}},{"doi":"10.1002/cncr.70371","pmid":"42186347","title":"Genetic ancestry–concordant ceramide metabolism and response to androgen receptor pathway inhibition in metastatic castration‐resistant prostate cancer","journal_title":"Cancer","journal_issn":"0008-543X","published_at":"2026-05-26T00:00:00.000Z","url":"https://doi.org/10.1002/cncr.70371","source_score":35,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-31T13:35:29.949Z","updated_at":"2026-05-31T13:35:29.949Z","tags":[{"paper_doi":"10.1002/cncr.70371","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"brand","value":"Erleada","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"brand","value":"Yonsa","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"condition","value":"Metastatic Castration-Resistant Prostate Cancer","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"generic","value":"abiraterone","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"generic","value":"apalutamide","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"modality","value":"Androgen Receptor Pathway Inhibitor","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"modality","value":"Ceramide Metabolomics","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"sample_size","value":"n=109","value_numeric":109},{"paper_doi":"10.1002/cncr.70371","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"warning","value":"Ancestry was self-reported or categorized as Black/White — the degree to which genetic ancestry was formally determined is not fully detailed in the abstract.","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"warning","value":"Brand name tags (Erleada, Yonsa) are inferred from the generic drug names; the abstract does not explicitly name branded formulations.","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"warning","value":"Sample sizes are small (n=44 in Abi Race, n=65 in PANTHER evaluable for metabolomics), so effect estimates should be interpreted cautiously.","value_numeric":null},{"paper_doi":"10.1002/cncr.70371","tag_type":"warning","value":"Study design is labeled 'Prospective Cohort' based on the described prospective trials with embedded metabolomic sub-studies; it is not a standalone RCT of ceramide modulation.","value_numeric":null}],"summaries":{"what_studied":"This study examined ceramide metabolite levels and their association with outcomes in Black and White patients with mCRPC treated with androgen receptor pathway inhibition (ARPI) — specifically abiraterone and apalutamide — across two prospective trials (Abi Race: 22 Black, 22 White; PANTHER: 28 Black, 37 White), measuring fasting serum sphingolipids pretreatment and on-treatment.","key_result":"Black patients had lower pretreatment total ceramide levels but higher pretreatment C24:C16 ceramide ratios than White patients. During ARPI, C24:C16 ratios fell in Black patients but rose in most White patients. Higher Cer(d18:1/20:0) was linked to shorter radiographic PFS and worse OS specifically in Black patients receiving apalutamide and abiraterone.","limitations":"Small sample sizes (total n=109 evaluable patients across both trials) limit statistical power and generalizability. Ancestry was categorized as Black or White, which may not fully capture the genetic diversity within these groups. Causal mechanisms linking ceramide shifts to treatment resistance are not established.","practice_takeaway":"Ceramide metabolite profiles — especially the C24:C16 ratio and Cer(d18:1/20:0) — differ by genetic ancestry and associate with ARPI outcomes in mCRPC. These biomarkers may eventually help identify Black patients at higher risk of shorter progression-free and overall survival, though prospective validation in larger cohorts is needed before clinical application."}},{"doi":"10.1097/ju.0000000000005131","pmid":"42171515","title":"First-Line Systemic Treatments of Metastatic Hormone-Sensitive Prostate Cancer: Updated Systematic Review and Network Meta-Analysis","journal_title":"Journal of Urology","journal_issn":"0022-5347","published_at":"2026-05-22T00:00:00.000Z","url":"https://doi.org/10.1097/ju.0000000000005131","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-14T13:24:59.421Z","updated_at":"2026-08-14T13:24:59.421Z","tags":[{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"brand","value":"Erleada","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"brand","value":"Nubeqa","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"brand","value":"Pluvicto","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"brand","value":"Xtandi","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"brand","value":"Zytiga","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"condition","value":"Metastatic Hormone-Sensitive Prostate Cancer","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"generic","value":"abiraterone","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"generic","value":"apalutamide","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"generic","value":"capivasertib","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"generic","value":"darolutamide","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"generic","value":"docetaxel","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"generic","value":"enzalutamide","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"generic","value":"lutetium-177 PSMA-617","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"generic","value":"niraparib","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"modality","value":"AKT Inhibitor","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"modality","value":"Androgen Deprivation Therapy","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"modality","value":"Androgen Receptor Pathway Inhibitor","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"modality","value":"PARP Inhibitor","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"modality","value":"Radioligand Therapy","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"modality","value":"Taxane Chemotherapy","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"sample_size","value":"n=18689","value_numeric":18689},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"study_design","value":"Network Meta-Analysis","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"warning","value":"Biomarker-driven trials (AMPLITUDE, CAPItello-281, PSMAddition) were excluded from the NMA due to selected populations and evaluated qualitatively only; OS results are immature for all three.","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"warning","value":"PARPi+ARPI+ADT OS data were not available for inclusion in the NMA; OS benefit for this triplet remains unknown.","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"warning","value":"Several included trials had open-label designs, introducing risk of bias in investigator-assessed progression endpoints.","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"warning","value":"The impact_flag 'practice_changing' reflects the high-certainty subgroup finding for docetaxel triplet in high-volume disease and the emerging biomarker-driven data; the all-comer analysis does not confirm a practice change for unselected patients.","value_numeric":null},{"paper_doi":"10.1097/ju.0000000000005131","tag_type":"warning","value":"The NMA grouped all ARPIs (abiraterone, apalutamide, darolutamide, enzalutamide, orteronel, rezvilutamide) as a single class to preserve network connectivity; class-level effects may mask agent-specific differences.","value_numeric":null}],"summaries":{"what_studied":"This updated systematic review and network meta-analysis (NMA) compared the efficacy and safety of first-line systemic combination therapies for metastatic hormone-sensitive prostate cancer (mHSPC) across 23 RCTs (n=18,689), searched through March 2026. Outcomes included progression-free survival (PFS), overall survival (OS), and severe adverse events (AEs), with a separate systematic review of biomarker-driven trials (AMPLITUDE, CAPItello-281, PSMAddition).","key_result":"No triplet regimen showed a statistically significant OS benefit over ARPI+ADT in all-comers. However, **docetaxel+ARPI+ADT** significantly improved OS in high-volume disease (HR 0.76, 95% CI 0.61–0.95; high certainty). For PFS, docetaxel+ARPI+ADT (HR 0.66, 95% CI 0.43–1.01; moderate certainty) and PARPi+ARPI+ADT (HR 0.55, 95% CI 0.23–1.34; low certainty) showed clinically relevant but non-significant trends vs. ARPI+ADT. In biomarker-selected populations: niraparib+abiraterone improved rPFS in HRR-mutated mHSPC (HR 0.63); capivasertib+abiraterone improved rPFS in PTEN-deficient mHSPC (HR 0.81); Lu-177-PSMA+ARPI+ADT improved rPFS in PSMA-positive mHSPC (HR 0.72); OS data remain immature for all three.","limitations":"- Direct head-to-head comparisons between key triplet regimens were unavailable, requiring reliance on indirect NMA contrasts with interstudy heterogeneity.\n- Combining radiographic and clinical PFS endpoints introduced heterogeneity; earlier trials used conventional imaging vs. more sensitive modalities in recent trials, risking stage migration bias.\n- PARPi-, PSMA-, and AKT-based evidence comes from single trials with immature OS data and small phase II samples, yielding low or very low certainty.","practice_takeaway":"For patients with **high-volume mHSPC**, docetaxel+ARPI+ADT offers a proven OS benefit (HR 0.76; high certainty) and should be preferred. For patients with specific biomarkers (HRR mutation, PTEN loss, or PSMA-positive disease), targeted intensification with PARPi, AKT inhibitor, or radioligand therapy respectively shows rPFS benefit—but OS data are still maturing, so treatment decisions must weigh distinct toxicity profiles against uncertain long-term gains."}},{"doi":"10.1200/jco-25-02834","pmid":"41744290","title":"Trial Design and Objectives for Patients With Prostate Cancer: Recommendations From the Prostate Cancer Working Group 4","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-02-26T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13132095/","source_score":61,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-02","doi":"10.1200/jco-25-02834","days":"14","issn":"0732-183X","rank":"9","field":"Clinical Medicine","score":"61","category":"Oncology","categories":["Oncology"],"_categories":["Oncology"]},"pubmed":{"doi":"10.1200/JCO-25-02834","title":"Trial Design and Objectives for Patients With Prostate Cancer: Recommendations From the Prostate Cancer Working Group 4.","journal":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology","methods":"","results":"PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)-defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework.","abstract":"$30","keywords":[],"pubmed_id":"41744290","conclusions":"PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator-naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.","publication_date":"2026-02-26T00:00:00"},"crossref":{"DOI":"10.1200/jco-25-02834","URL":"https://doi.org/10.1200/jco-25-02834","ISSN":["0732-183X","1527-7755"],"link":[{"URL":"https://ascopubs.org/doi/pdfdirect/10.1200/JCO-25-02834","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"1249-1265","type":"journal-article","issue":"13","score":1,"title":["Trial Design and Objectives for Patients With Prostate Cancer: Recommendations From the Prostate Cancer Working Group 4"],"author":[{"given":"Andrew J.","family":"Armstrong","sequence":"first","affiliation":[{"name":"Department of Medicine, Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, Durham, NC"}]},{"given":"Michael J.","family":"Morris","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}]},{"given":"Wassim","family":"Abida","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}]},{"given":"Rahul R.","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"San Francisco Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA"}]},{"given":"Emmanuel S.","family":"Antonarakis","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota, Minneapolis, MN"}]},{"given":"Gerhardt","family":"Attard","sequence":"additional","affiliation":[{"name":"University College London Cancer Institute, London, United Kingdom"}]},{"given":"Himisha","family":"Beltran","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute, Boston, MA"}]},{"given":"Alan","family":"Bryce","sequence":"additional","affiliation":[{"name":"City of Hope Cancer Center, Goodyear, AZ"}]},{"given":"Michael A.","family":"Carducci","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD"}]},{"given":"Heather H.","family":"Cheng","sequence":"additional","affiliation":[{"name":"University of Washington and Fred Hutchinson Cancer Center, Seattle, WA"}]},{"given":"Delphine L.","family":"Chen","sequence":"additional","affiliation":[{"name":"University of Washington and Fred Hutchinson Cancer Center, Seattle, WA"}]},{"given":"Kim N.","family":"Chi","sequence":"additional","affiliation":[{"name":"BC Cancer Agency, Vancouver, BC, Canada"}]},{"given":"Daniel S.","family":"Childs","sequence":"additional","affiliation":[{"name":"Department of Oncology, Mayo Clinic, Rochester, MN"}]},{"given":"William","family":"Dahut","sequence":"additional","affiliation":[{"name":"American Cancer Society, Atlanta, GA"}]},{"given":"Louise","family":"Emmett","sequence":"additional","affiliation":[{"name":"Department of Theranostics and Nuclear Medicine, St Vincent's Hospital, Sydney, Australia"}]},{"given":"Karim","family":"Fizazi","sequence":"additional","affiliation":[{"name":"Department of Cancer Medicine, Centre Oscar Lambret, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France"}]},{"given":"Andrei","family":"Gafita","sequence":"additional","affiliation":[{"name":"Department of Radiology and Radiological Sciences, Johns Hopkins Theranostics Center, Johns Hopkins University, Baltimore, MD"}]},{"given":"Daniel J.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, Durham, NC"}]},{"given":"Ken","family":"Hermann","sequence":"additional","affiliation":[{"name":"Universitätsklinikum Essen, Essen, Germany"}]},{"given":"Michael S.","family":"Hofman","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre, Melbourne, VIC, Australia"},{"name":"University of Melbourne, Parkville, VIC, Australia"}]},{"given":"Thomas","family":"Hope","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, San Francisco, CA"}]},{"given":"Maha","family":"Hussain","sequence":"additional","affiliation":[{"name":"Robert H. 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level of evidence reflects expert opinion.","value_numeric":null}],"summaries":{"what_studied":"PCWG4, an international expert committee convened 2016–2025, updated clinical trial design guidance for advanced prostate cancer — covering disease-state terminology, eligibility criteria, imaging (with a focus on PSMA-PET), response/progression end points, biomarker frameworks, and patient-reported outcomes across the full disease spectrum from localized to metastatic androgen pathway modulator–resistant (APMR) disease.","key_result":"Key recommendations include: (1) replacing 'castration-sensitive/resistant' with androgen pathway modulation–naïve/sensitive/resistant (APMN/APMS/APMR) terminology; (2) incorporating PSMA-PET as non-investigational for staging but investigational for response assessment; (3) updating the bone progression rule — ≥6 new lesions on a restaging scan no longer require a confirmatory scan (vs. the prior 2+2 rule for all cases); (4) endorsing four near-term candidate response biomarkers: pathologic response, PSA declines/nadir, CTC0, and ctDNA decline; and (5) defining PSA progression in the APM setting as any confirmed rise ≥0.2 ng/mL from baseline/nadir on two measurements ≥21 days apart.","limitations":"This is a consensus guideline document, not a primary clinical trial — recommendations are expert-based and many proposed PSMA-PET criteria (e.g., SUV-based response, PET-defined rPFS) require prospective phase III validation. The document acknowledges that most novel biomarkers (ctDNA, CTC0, PSA declines) are not yet validated surrogates for OS or regulatory approval.","practice_takeaway":"Clinicians designing or interpreting prostate cancer trials should adopt APMN/APMS/APMR terminology and obtain PSMA-PET at baseline where feasible, while tracking CT/bone scan findings independently. For bone progression on bone scintigraphy or PSMA-PET, a confirmatory scan is no longer required when ≥6 new lesions are seen — act on that finding promptly rather than waiting."}}],"initialOffset":5,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"brand","value":"Erleada"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Brands","href":"/hub/tag/brand"},{"name":"Erleada"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"brand","hub_tag_value":"Erleada"}}}]]

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