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\":\"abiraterone: generic Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on abiraterone (generic). Clinician-written summaries and actionable practice insights. 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not explicitly stated in the abstract.","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.08.012","tag_type":"warning","value":"FRH data were derived from Hospital Episode Statistics (HES) in England only, limiting generalisability to other healthcare systems.","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.08.012","tag_type":"warning","value":"Study design is a secondary analysis; causal inference is limited by residual confounding (e.g., unrecorded bone-protective therapy use).","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.08.012","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied because this finding directly counters prior meta-analytic signals suggesting ARPIs increase fracture risk, but it is based on a secondary analysis rather than a primary pre-specified endpoint.","value_numeric":null}],"summaries":{"what_studied":"This secondary analysis of two STAMPEDE phase 3 trials evaluated whether abiraterone-based treatment intensification (SOC+AAP ± enzalutamide) increased fracture-related hospitalisation (FRH) compared to standard of care (SOC) alone in 3,102 patients with newly diagnosed high-risk non-metastatic (M0) or metastatic (M1) prostate cancer in England, with up to 5-year follow-up.","key_result":"In M1 disease, 5-year FRH incidence was **lower** with SOC+AAP vs. SOC alone (22% vs. 30%; SDHR 0.77, 95% CI 0.59–0.99; p=0.04), and lower still with SOC+AAP+Enza vs. SOC alone (28% vs. 38%; SDHR 0.69, 95% CI 0.54–0.88; p=0.002); no significant difference was seen in M0 patients.","limitations":"- Only hospitalised fractures were captured, likely **underestimating** total fracture burden.\n- No baseline bone mineral density or fracture-risk assessment was available.\n- Longitudinal bone-protective therapy use was not systematically recorded, which may confound results.","practice_takeaway":"Clinicians can reassure patients with metastatic prostate cancer that abiraterone-based intensification does not increase — and may actually reduce — fracture-related hospitalisation, likely through better control of bone metastases. Bone-protective strategies remain important, but ARPI-related fracture risk concerns should not deter treatment intensification in M1 disease."}},{"doi":"10.1016/j.euo.2026.07.014","pmid":"42595654","title":"Efficacy of Olaparib Plus Abiraterone for Patients with Metastatic Castration-resistant Prostate Cancer and Single Homologous Recombination Repair Gene Mutations in PROpel","journal_title":"European Urology Oncology","journal_issn":"2588-9311","published_at":"2026-08-13T00:00:00.000Z","url":"https://doi.org/10.1016/j.euo.2026.07.014","source_score":15,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-17T13:33:11.214Z","updated_at":"2026-08-17T13:33:11.214Z","tags":[{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"brand","value":"Lynparza","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"brand","value":"Zytiga","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"condition","value":"Metastatic Castration-Resistant Prostate Cancer","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"generic","value":"abiraterone","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"generic","value":"olaparib","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"modality","value":"Androgen Receptor Pathway Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"modality","value":"PARP Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"sample_size","value":"n=796","value_numeric":796},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"warning","value":"Brand name 'Zytiga' is used for abiraterone; prednisone co-administration (standard with abiraterone) is not mentioned in the abstract.","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"warning","value":"The level of evidence is tagged as 2 (subgroup analysis of a phase 3 RCT); the primary trial is level 1, but these subgroup findings carry inherent limitations.","value_numeric":null},{"paper_doi":"10.1016/j.euo.2026.07.014","tag_type":"warning","value":"The total sample size (n=796) is inferred from the full PROpel trial; the abstract does not explicitly state the exact N. The HRRm subgroup size is not given as a precise integer.","value_numeric":null}],"summaries":{"what_studied":"This pre-specified subgroup analysis of PROpel (phase 3, double-blind RCT) examined efficacy of olaparib plus abiraterone vs. placebo plus abiraterone as first-line therapy in patients with mCRPC harboring single homologous recombination repair gene mutations (HRRm), determined via tumor tissue and ctDNA assays.","key_result":"Among the 28.4% of patients with an HRRm, BRCA2-mutated patients showed the strongest benefit: rPFS HR 0.20 (95% CI 0.08–0.44) and OS HR 0.20 (95% CI 0.07–0.48). ATM and CDK12 single-gene mutations showed numerically favorable but non-significant rPFS and OS HRs. Overall (biomarker-unselected), olaparib plus abiraterone improved rPFS (HR 0.66; p<0.0001) and median OS by 7.4 months (42.1 vs. ~34.7 mo).","limitations":"- Subgroups for most single HRRm genes other than BRCA2, ATM, and CDK12 had fewer than 5 events per arm, severely limiting interpretation.\n- HRRm status was determined by aggregating two assay platforms (tumor tissue + ctDNA), which may introduce heterogeneity in mutation detection.\n- ATM and CDK12 confidence intervals were wide and crossed 1.0, so benefit in these subgroups remains uncertain.","practice_takeaway":"Olaparib plus abiraterone provides a strong first-line benefit in mCRPC patients with BRCA2 mutations (rPFS and OS HR ~0.20) and should be prioritized in this group. For ATM and CDK12 single-gene mutations, benefit is numerically present but not statistically confirmed, so clinical judgment is needed."}},{"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":"10.1007/s11523-026-01234-z","pmid":"42568016","title":"Impact of PSA Nadir on Outcomes in Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review and Reconstructed Individual Patient Data Meta-analysis","journal_title":"Targeted Oncology","journal_issn":"1776-2596","published_at":"2026-08-07T00:00:00.000Z","url":"https://doi.org/10.1007/s11523-026-01234-z","source_score":22,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-12T13:26:14.862Z","updated_at":"2026-08-12T13:26:14.862Z","tags":[{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"condition","value":"Metastatic Hormone-Sensitive Prostate Cancer","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"condition","value":"Prostate Cancer","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"generic","value":"abiraterone","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"generic","value":"apalutamide","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"generic","value":"darolutamide","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"generic","value":"docetaxel","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"generic","value":"enzalutamide","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"modality","value":"Androgen Receptor Pathway Inhibitor","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"modality","value":"Chemotherapy","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"sample_size","value":"n=1638","value_numeric":1638},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"study_design","value":"Systematic Review and Meta-Analysis","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"warning","value":"IPD was reconstructed from published Kaplan-Meier curves using software (IPDfromKM), not sourced directly from trial databases—minor inaccuracies in patient-level data are possible, as noted in the supplementary table comparisons.","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"warning","value":"The meta-analysis did not register a protocol or perform a GRADE certainty-of-evidence assessment, limiting confidence in the strength of recommendations.","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"warning","value":"The OS analysis includes 1,638 patients while the PFS analysis includes only 1,104 patients—not all studies contributed to both endpoints, which should be considered when interpreting results.","value_numeric":null},{"paper_doi":"10.1007/s11523-026-01234-z","tag_type":"warning","value":"The PSA nadir cutoff varied across included studies (some used ≤0.1 ng/mL, others ≤0.2 ng/mL); the pooled analysis used ≤0.2 as the primary threshold, which may affect comparability.","value_numeric":null}],"summaries":{"what_studied":"This reconstructed individual patient data (IPD) meta-analysis of 8 studies evaluated the prognostic value of PSA nadir (≤0.2 vs. >0.2 ng/mL) on overall survival (OS) and progression-free survival (PFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen receptor pathway inhibitors (ARPIs) or docetaxel.","key_result":"Achieving a PSA nadir ≤0.2 ng/mL was strongly associated with better outcomes: median PFS not reached vs. 12.1 months (HR 0.19, 95% CI 0.16–0.23, p<0.0001) and median OS 92.8 vs. 34 months (HR 0.27, 95% CI 0.22–0.33, p<0.0001), across 1,638 patients (OS) and 1,104 patients (PFS).","limitations":"- IPD was reconstructed from Kaplan-Meier curves rather than obtained directly from trial investigators, introducing potential reconstruction error.\n- The PSA nadir threshold of ≤0.2 ng/mL was not uniform across all included studies (some used ≤0.1), creating heterogeneity in the defining cutpoint.\n- No formal certainty-of-evidence (e.g., GRADE) assessment was conducted, and reporting bias assessment was not performed.","practice_takeaway":"In mHSPC patients on ARPIs or docetaxel, achieving a PSA nadir ≤0.2 ng/mL is a strong early marker of favorable prognosis—clinicians can use this threshold to flag patients at high risk of early progression and inform closer monitoring or discussion of treatment intensification."}},{"doi":"10.1038/s41391-026-01145-0","pmid":"42557372","title":"Clinical and genomic determinants of extraordinary response and resistance to androgen receptor pathway inhibitors in men with metastatic androgen pathway modulator sensitive (APMS) prostate cancer","journal_title":"Prostate Cancer and Prostatic Diseases","journal_issn":"1365-7852","published_at":"2026-08-05T00:00:00.000Z","url":"https://doi.org/10.1038/s41391-026-01145-0","source_score":14,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-09T13:25:05.887Z","updated_at":"2026-08-09T13:25:05.887Z","tags":[{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"condition","value":"Metastatic Castration-Sensitive Prostate Cancer","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"condition","value":"Prostate Cancer","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"generic","value":"abiraterone","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"generic","value":"apalutamide","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"generic","value":"docetaxel","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"generic","value":"enzalutamide","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"modality","value":"Androgen Deprivation Therapy","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"modality","value":"Androgen Receptor Pathway Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"sample_size","value":"n=224","value_numeric":224},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"warning","value":"Molecular testing temporal windows differed between ER and NR groups (within 6 vs. 3 months of ARPI start), which may introduce minor confounding from treatment-emergent alterations.","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"warning","value":"Results for some genes (BRCA2, SPOP, RAD21) are based on small numbers and should be interpreted cautiously; no correction for multiple testing was applied.","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"warning","value":"Specific ARPIs used per patient are not individually detailed; the cohort likely includes enzalutamide, abiraterone, apalutamide, and darolutamide — drug-specific subgroup results are not reported.","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01145-0","tag_type":"warning","value":"The 'androgen pathway modulator sensitive (APMS)' terminology follows PCWG4 conventions and is equivalent to the more familiar 'metastatic castration-sensitive' or 'hormone-sensitive' prostate cancer labels.","value_numeric":null}],"summaries":{"what_studied":"This single-institution retrospective study (Duke Health, 2015–2024) evaluated clinical and genomic predictors of exceptional response (ER; PFS >53.36 months) versus non-response (NR; PFS <10.41 months) to ADT plus ARPI in 224 men with metastatic androgen pathway modulator sensitive (APMS) prostate cancer, with molecular testing available in 154 (69%).","key_result":"TP53 alteration (PFS HR 1.60, OS HR 1.91) and MYC gain (PFS HR 2.01, OS HR 3.81; multivariable OS HR 4.41) independently predicted worse outcomes. Co-alteration of ≥1 tumor suppressor gene plus ≥1 proliferative gene strongly associated with NR (58% vs. 7.7% in ER, p=0.002). Low-volume disease (OR 12.4), ECOG 0, higher hemoglobin/albumin, and normal alkaline phosphatase predicted ER. Achieving PSA nadir <0.2 ng/mL within 12 months was seen in 100% of ER vs. 21% of NR and carried a >5-fold increased likelihood of exceptional response.","limitations":"- Single-institution design with potential selection bias and incomplete real-world data.\n- Molecular testing was heterogeneous (tissue NGS vs. cfDNA) and available in only 69% of APMS patients, likely enriched for those who progressed.\n- Small subgroup numbers for some genes (e.g., BRCA2, SPOP, RAD21) limit power; results are hypothesis-generating without multiple testing correction.","practice_takeaway":"Pre-treatment molecular profiling for TP53, MYC, and tumor suppressor gene co-alterations can help identify men with APMS at high risk of early ARPI failure — these patients may warrant closer monitoring or intensified treatment strategies. PSA nadir <0.2 ng/mL at 12 months is a practical early landmark to assess depth of response and long-term prognosis."}},{"doi":"10.1016/j.annonc.2026.05.708","pmid":"42250604","title":"Multimodal Artificial Intelligence Prediction of Abiraterone Efficacy in Two STAMPEDE Phase 3 Trials of Non-Metastatic Very High-Risk Prostate Cancer","journal_title":"Annals of Oncology","journal_issn":"0923-7534","published_at":"2026-06-06T00:00:00.000Z","url":"https://doi.org/10.1016/j.annonc.2026.05.708","source_score":23,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-16T13:54:27.872Z","updated_at":"2026-06-16T13:54:27.872Z","tags":[{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"condition","value":"Prostate Cancer","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"generic","value":"abiraterone","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"modality","value":"Androgen Biosynthesis Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"modality","value":"Androgen Deprivation Therapy","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"modality","value":"Digital Pathology AI Biomarker","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"sample_size","value":"n=1137","value_numeric":1137},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"study_design","value":"Post-Hoc Analysis of Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"warning","value":"Level of evidence set to 2 based on RCT data origin, but the post-hoc design technically downgrades inferential strength.","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously given the post-hoc design; prospective confirmation would strengthen this designation.","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"warning","value":"The study is a post-hoc analysis; the MMAI tool is not yet prospectively validated for this specific predictive use case.","value_numeric":null},{"paper_doi":"10.1016/j.annonc.2026.05.708","tag_type":"warning","value":"Two sequential STAMPEDE trials with no shared controls were pooled — subtle protocol differences between trials could influence pooled estimates.","value_numeric":null}],"summaries":{"what_studied":"A multimodal AI (MMAI) digital pathology model was evaluated as a predictive biomarker for abiraterone benefit in 1,137 non-metastatic, clinically very high-risk prostate cancer patients from two STAMPEDE phase 3 trials, randomized to long-term ADT (LT-ADT) alone vs. LT-ADT plus abiraterone; primary endpoint was metastasis-free survival (MFS).","key_result":"MMAI very high-risk patients (N=268, ~24%) had a large abiraterone benefit (HR 0.47; 95% CI 0.31–0.70; 5-yr MFS 62% → 81%), while MMAI standard high-risk patients (N=869) showed no significant benefit (HR 0.83; 95% CI 0.63–1.09; 5-yr MFS 82% vs. 84%); interaction p=0.02.","limitations":"- Post-hoc analysis of RCT data limits causal inference and requires prospective validation.\n- MMAI threshold (75th percentile) was pre-specified but derived from prior work, not this dataset.\n- Two sequential trials with no shared controls were pooled, introducing potential heterogeneity.","practice_takeaway":"MMAI scoring of diagnostic biopsy pathology could help identify the ~24% of very high-risk localized prostate cancer patients who derive clear MFS benefit from adding abiraterone to LT-ADT, potentially sparing the majority from unnecessary toxicity and cost. Prospective validation is needed before routine clinical use."}},{"doi":"10.1038/s41391-026-01124-5","pmid":"42209844","title":"EMETPRO: a multicentric, international, retrospective analysis evaluating patients with metastatic hormone-sensitive prostate cancer with early progression","journal_title":"Prostate Cancer and Prostatic Diseases","journal_issn":"1365-7852","published_at":"2026-05-29T00:00:00.000Z","url":"https://doi.org/10.1038/s41391-026-01124-5","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-08T13:46:34.969Z","updated_at":"2026-06-08T13:46:34.969Z","tags":[{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"condition","value":"Metastatic Castration-Resistant Prostate Cancer","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"condition","value":"Metastatic Hormone-Sensitive Prostate Cancer","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"generic","value":"abiraterone","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"generic","value":"apalutamide","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"generic","value":"darolutamide","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"generic","value":"docetaxel","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"generic","value":"enzalutamide","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"modality","value":"Androgen Deprivation Therapy","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"modality","value":"Androgen Receptor Pathway Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"modality","value":"Taxane Chemotherapy","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"sample_size","value":"n=401","value_numeric":401},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"study_design","value":"Retrospective Multicenter Registry Study","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"warning","value":"Specific ARPIs used are not broken down in the available abstract/results text; brand and generic tags reflect agents mentioned in the reference list and background context rather than confirmed per-patient data.","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"warning","value":"The level of evidence is rated 4 given the retrospective, non-randomized, registry design.","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"warning","value":"The study spans 2005–2023, meaning a substantial proportion of patients were treated before combination therapy (ARPI+ADT) became standard, which may confound comparisons between treatment groups.","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01124-5","tag_type":"warning","value":"The total sample size of 401 is inferred by summing the three reported subgroups (201 + 124 + 76); the abstract does not explicitly state the total N.","value_numeric":null}],"summaries":{"practice_takeaway":"Patients with early progression on mHSPC therapy face very poor survival (median OS under 27 months) regardless of the subsequent mCRPC treatment used — no clear best next step has emerged. Clinicians should consider enrolling these patients in clinical trials, as optimal first-line mCRPC therapy remains an unmet need.","what_studied":"This multicentric retrospective registry (EMETPRO) evaluated 401 patients with metastatic hormone-sensitive prostate cancer (mHSPC) who had early progression (EP): ≤6 months on ADT+docetaxel or ADT+ARPI, or ≤9 months on ADT monotherapy, treated between 2005 and 2023 across international centers.","key_result":"Outcomes were poor across all groups. ADT monotherapy patients had median PFS 6.8 months and median OS 26.4 months. ADT+docetaxel patients had median PFS 4.9 months and OS 18.6 months. ADT+ARPI patients had median PFS 5.6 months and OS 19.5 months. Neither first-line mCRPC treatment choice nor genetic profile was associated with improved survival.","limitations":"Retrospective design with data spanning 2005–2023 introduces heterogeneity in treatment eras and standards. Genetic profiling was not available for all patients, limiting biomarker analysis. No randomization; treatment allocation was at physician discretion."}},{"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. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL"}]},{"given":"W. Kevin","family":"Kelly","sequence":"additional","affiliation":[{"name":"Sidney Kimmel School of Medicine at Thomas Jefferson University, Philadelphia, PA"}]},{"given":"Elizabeth","family":"Kessler","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine, Aurora, CO"}]},{"given":"Phillip H.","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Radiology, City of Hope National Medical Center, Duarte, CA"}]},{"given":"Joshua","family":"Lang","sequence":"additional","affiliation":[{"name":"University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, WI"}]},{"given":"Glenn","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, WI"}]},{"given":"Catherine H.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD"}]},{"given":"Alicia K.","family":"Morgans","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute, Boston, MA"}]},{"given":"Rana R.","family":"McKay","sequence":"additional","affiliation":[{"name":"University of California San Diego, San Diego, CA"}]},{"given":"David","family":"Nanus","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine, New York, NY"},{"name":"Weill Cornell Medicine-NewYork Presbyterian Hospital, New York, NY"}]},{"given":"Peter","family":"Nelson","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center, Seattle, WA"}]},{"given":"Channing","family":"Paller","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD"}]},{"given":"Zachery R.","family":"Reichert","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Michigan, Ann Arbor, MI"}]},{"given":"Charles J.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}]},{"given":"A. Oliver","family":"Sartor","sequence":"additional","affiliation":[{"name":"Transformational Prostate Cancer Research Center, LCMC Health, New Orleans, LA"}]},{"given":"Heiko","family":"Schöder","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}]},{"given":"Lawrence H.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY"}]},{"given":"Nima","family":"Sharifi","sequence":"additional","affiliation":[{"name":"University of Miami Miller School of Medicine, Miami, FL"}]},{"given":"Walter M.","family":"Stadler","sequence":"additional","affiliation":[{"name":"City of Hope Cancer Center, Chicago, IL"}]},{"given":"Mark","family":"Stein","sequence":"additional","affiliation":[{"name":"Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY"}]},{"given":"Cora N.","family":"Sternberg","sequence":"additional","affiliation":[{"name":"Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY"},{"name":"Department of Medicine, Sandra and Edward Meyer Cancer Center, New York Presbyterian, New York, NY"}]},{"given":"Russell Z.","family":"Szmulewitz","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Chicago, Chicago, IL"}]},{"given":"Scott T.","family":"Tagawa","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY"}]},{"given":"Alexandra O.","family":"Sokolova","sequence":"additional","affiliation":[{"name":"Hematology Oncology, Oregon Health and Science University, Portland, OR"}]},{"given":"Alex W.","family":"Wyatt","sequence":"additional","affiliation":[{"name":"Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada"},{"name":"Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada"}]},{"given":"Kosj","family":"Yamoah","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL"},{"name":"James A. 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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":10,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"generic","value":"abiraterone"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Generics","href":"/hub/tag/generic"},{"name":"abiraterone"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"generic","hub_tag_value":"abiraterone"}}}]]

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