2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T764,In patients who received enzalutamide, we characterized the development of radiographic progression (rPD) without prostate-specific antigen (PSA) rise or progression in metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC). We conducted a post hoc analysis in two phase III trials (N = 2,551; ARCHES [ClinicalTrials.gov identifier: NCT02677896]; PROSPER [ClinicalTrials.gov identifier: NCT02003924]) for co-occurrence of rPD ± Prostate Cancer Working Group 2/3-defined PSA progression, and rPD ± any PSA rise from baseline/nadir by treatment. Kaplan-Meier methods were used for overall survival (OS) outcomes. In ARCHES, 3.5% and 8.5% of 574 patients with mHSPC treated with enzalutamide plus androgen-deprivation therapy (ADT) had no PSA rise or PSA progression at rPD, respectively. Of 79 patients with rPD who received enzalutamide plus ADT, 25.3% had no PSA rise and 62.0% did not meet PSA progression criteria compared with 7.4% and 38.3% of 188 patients with rPD treated with ADT alone, respectively. In PROSPER, 4.4% and 10.3% of 933 patients with nmCRPC treated with enzalutamide plus ADT had no PSA rise or PSA progression, respectively, at rPD. However, of 187 patients with rPD who received enzalutamide plus ADT, 21.9% had no PSA rise and 51.3% did not meet PSA progression criteria compared with 3.6% and 18.8% of 224 patients treated with placebo/ADT, respectively. Liver metastases were >5-fold higher in enzalutamide-treated patients with rPD events versus control, although sample size was small. Compared with no rPD, enzalutamide-treated patients with rPD ± PSA rise or progression had worse OS. Given the frequent discordance and poor prognosis of imaging-based progression in the absence of PSA changes during enzalutamide treatment in mHSPC and nmCRPC, periodic surveillance using imaging is recommended.31:Tb70, PURPOSE In patients who received enzalutamide, we characterized the development of radiographic progression (rPD) without prostate-specific antigen (PSA) rise or progression in metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC). Methods We conducted a post hoc analysis in two phase III trials (N = 2,551; ARCHES [ClinicalTrials.gov identifier: NCT02677896 ]; PROSPER [ClinicalTrials.gov identifier: NCT02003924 ]) for co-occurrence of rPD ± Prostate Cancer Working Group 2/3-defined PSA progression, and rPD ± any PSA rise from baseline/nadir by treatment. Kaplan-Meier methods were used for overall survival (OS) outcomes. RESULTS In ARCHES, 3.5% and 8.5% of 574 patients with mHSPC treated with enzalutamide plus androgen-deprivation therapy (ADT) had no PSA rise or PSA progression at rPD, respectively. Of 79 patients with rPD who received enzalutamide plus ADT, 25.3% had no PSA rise and 62.0% did not meet PSA progression criteria compared with 7.4% and 38.3% of 188 patients with rPD treated with ADT alone, respectively. In PROSPER, 4.4% and 10.3% of 933 patients with nmCRPC treated with enzalutamide plus ADT had no PSA rise or PSA progression, respectively, at rPD. However, of 187 patients with rPD who received enzalutamide plus ADT, 21.9% had no PSA rise and 51.3% did not meet PSA progression criteria compared with 3.6% and 18.8% of 224 patients treated with placebo/ADT, respectively. Liver metastases were >5-fold higher in enzalutamide-treated patients with rPD events versus control, although sample size was small. Compared with no rPD, enzalutamide-treated patients with rPD ± PSA rise or progression had worse OS. CONCLUSION Given the frequent discordance and poor prognosis of imaging-based progression in the absence of PSA changes during enzalutamide treatment in mHSPC and nmCRPC, periodic surveillance using imaging is recommended. 32:T747,Docetaxel improves survival in metastatic hormone-sensitive prostate cancer (mHSPC) and high-risk localized disease, but benefits vary substantially among patients. Without predictive biomarkers, clinicians cannot identify patients who will benefit, exposing many to unnecessary toxicity. We developed and validated an artificial intelligence-based pathology image classifier (APIC) to predict docetaxel benefit. We analyzed digitized H&E-stained biopsy specimens from two phase 3 trials: CHAARTED (286/790 patients with mHSPC) and NRG/RTOG 0521 (350/563 patients with high-risk localized disease). APIC used features capturing tumor-immune spatial interactions and nuclear heterogeneity. We evaluated the predictive value of APIC for docetaxel benefit on overall survival and castration-resistance using Cox proportional hazards with interaction terms. In CHAARTED, APIC-positive patients (56.7%) showed significant overall survival improvement with docetaxel (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.31-0.85; P = 0.008) and delayed castration-resistance (HR 0.48, 95% CI 0.33-0.71; P < 0.001), while APIC-negative patients (43.3%) showed no benefit (HR 1.31, 95% CI 0.71-2.44; P = 0.39). Treatment-APIC interactions were significant (P = 0.022 and P = 0.031). In NRG/RTOG 0521, APIC-positive patients (44.7%) demonstrated survival benefit (HR 0.49, 95% CI 0.26-0.92; P = 0.023), while APIC-negative patients (55.3%) showed no benefit. Treatment-APIC interaction was significant (P = 0.024). Predictive value remained significant after adjusting for clinical variables. Limitations include retrospective analysis and need for prospective validation. APIC predicts docetaxel benefit in both metastatic and localized prostate cancer, independent of clinical factors. Validation in triplet therapy with androgen receptor pathway inhibitors is needed.33:T9ef,Abstract Purpose: Docetaxel improves survival in metastatic hormone-sensitive prostate cancer (mHSPC) and high-risk localized disease, but benefits vary substantially among patients. Without predictive biomarkers, clinicians cannot identify patients who will benefit, exposing many to unnecessary toxicity. We developed and validated an artificial intelligence–based pathology image classifier (APIC) to predict docetaxel benefit. Experimental Design: We analyzed digitized hematoxylin and eosin–stained biopsy specimens from two phase 3 trials: CHAARTED (286/790 patients with mHSPC) and NRG/RTOG 0521 (350/563 patients with high-risk localized disease). APIC used features capturing tumor-immune spatial interactions and nuclear heterogeneity. We evaluated the predictive value of APIC for docetaxel benefit on overall survival (OS) and castration resistance using Cox proportional hazards with interaction terms. Results: In CHAARTED, APIC-positive patients (56.7%) showed significant OS improvement with docetaxel [HR, 0.52; 95% confidence interval (CI), 0.31–0.85; P = 0.008] and delayed castration resistance (HR, 0.48; 95% CI, 0.33–0.71; P < 0.001), whereas APIC-negative patients (43.3%) showed no benefit (HR, 1.31; 95% CI, 0.71–2.44; P = 0.39). Treatment–APIC interactions were significant (P = 0.022 and P = 0.031). In NRG/RTOG 0521, APIC-positive patients (44.7%) demonstrated survival benefit (HR, 0.49; 95% CI, 0.26–0.92; P = 0.023), whereas APIC-negative patients (55.3%) showed no benefit. Treatment–APIC interaction was significant (P = 0.024). Predictive value remained significant after adjusting for clinical variables. Limitations include retrospective analysis and need for prospective validation. Conclusions: APIC predicts docetaxel benefit in both metastatic and localized prostate cancers, independent of clinical factors. Validation in triplet therapy with androgen receptor pathway inhibitors is needed. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Metastatic Hormone-Sensitive Prostate Cancer: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Metastatic Hormone-Sensitive Prostate Cancer (condition). Clinician-written summaries and actionable practice insights. 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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":"10.1016/j.eururo.2026.04.014","pmid":"42457456","title":"EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer. Part II—2026 Update: Treatment of Relapsing and Metastatic Prostate Cancer","journal_title":"European Urology","journal_issn":"0302-2838","published_at":"2026-07-15T00:00:00.000Z","url":"https://doi.org/10.1016/j.eururo.2026.04.014","source_score":26,"is_retracted":false,"is_open_access":null,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":false},"created_at":"2026-07-21T13:34:33.976Z","updated_at":"2026-07-21T13:34:33.976Z","tags":[{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"condition","value":"Castration-Resistant Prostate Cancer","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"condition","value":"Metastatic Hormone-Sensitive Prostate Cancer","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"condition","value":"Prostate Cancer","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"modality","value":"Androgen Receptor Pathway Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"modality","value":"Metastasis-Directed Therapy","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"modality","value":"PARP Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"modality","value":"PSMA-Based Therapy","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"study_design","value":"Clinical Practice Guideline","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"warning","value":"Cost and reimbursement considerations are explicitly excluded from the recommendations, which may limit direct applicability in resource-constrained settings.","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"warning","value":"No specific sample size is applicable — this is a guidelines document, not a primary study. Level of evidence rated '1' reflects the guideline panel's systematic review process, not a single trial.","value_numeric":null},{"paper_doi":"10.1016/j.eururo.2026.04.014","tag_type":"warning","value":"Specific strength-of-recommendation grades for individual interventions are not detailed in the abstract; the full guideline document should be consulted for granular recommendations.","value_numeric":null}],"summaries":{"what_studied":"The 2026 EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines update covers treatment of relapsing, metastatic hormone-sensitive, and castration-resistant prostate cancer (PCa), based on a systematic literature review of evidence published between 2023 and 2025.","key_result":"Updated recommendations endorse risk-stratified salvage therapy for relapsing PCa and an expanded treatment toolkit for metastatic/castration-resistant disease — including ARPIs, PARP inhibitors and their combinations, metastasis-directed therapy, and PSMA-based therapy — each graded by strength of evidence.","limitations":"Recommendations do not account for variations in cost, reimbursement, or resource availability across healthcare systems; the review window is limited to 2023–2025, so very recent data may be excluded.","practice_takeaway":"Use risk stratification to guide salvage therapy after primary PCa treatment, and consider the expanded armamentarium — ARPIs, PARP inhibitors (alone or combined), and PSMA-targeted agents — when managing metastatic or castration-resistant disease. Always weigh local formulary access and reimbursement realities, as the guidelines do not factor these in."}},{"doi":"10.1016/j.euf.2026.06.014","pmid":"42366147","title":"Radioligand Therapy for Prostate Cancer – A Clinical Consultation Guide","journal_title":"European Urology Focus","journal_issn":"2405-4569","published_at":"2026-06-28T00:00:00.000Z","url":"https://doi.org/10.1016/j.euf.2026.06.014","source_score":5,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-06T13:36:15.342Z","updated_at":"2026-07-06T13:36:15.342Z","tags":[{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"brand","value":"Pluvicto","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"condition","value":"Metastatic Castration-Resistant Prostate Cancer","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"condition","value":"Metastatic Hormone-Sensitive Prostate Cancer","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"condition","value":"Prostate Cancer","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"generic","value":"lutetium Lu 177 vipivotide tetraxetan","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"modality","value":"PSMA-Targeted Therapy","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"modality","value":"Radioligand Therapy","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"study_design","value":"Clinical Practice Guideline / Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"warning","value":"Publication date (2026-06-28) is very recent relative to today's date (2026-07-06); downstream guideline updates may not yet reflect this review.","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"warning","value":"The generic name used ('lutetium Lu 177 vipivotide tetraxetan') reflects the FDA-approved RxNorm form; the paper refers to the compound as '[177Lu]Lu-PSMA-617'.","value_numeric":null},{"paper_doi":"10.1016/j.euf.2026.06.014","tag_type":"warning","value":"This paper is a narrative clinical consultation guide, not a primary trial — no new efficacy or safety data are reported. Level of evidence reflects expert review, not a controlled study.","value_numeric":null}],"summaries":{"what_studied":"This clinical consultation guide summarizes evidence, patient selection strategies, toxicity monitoring, and future directions for PSMA-targeted radioligand therapy ([177Lu]Lu-PSMA-617) in prostate cancer, drawing on landmark trials (VISION, TheraP, PSMAfore) across mCRPC and emerging earlier-line settings.","key_result":"VISION, TheraP, and PSMAfore trials established that [177Lu]Lu-PSMA-617 improves overall survival, progression-free survival, and biochemical response rates in mCRPC; evidence is expanding to taxane-naïve disease, metastatic hormone-sensitive prostate cancer, and neoadjuvant settings.","limitations":"This is a narrative consultation guide, not a primary study — no new patient-level data are presented. Emerging imaging biomarkers for patient selection are described as investigational only. Evidence for earlier-line use (mHSPC, neoadjuvant) remains preliminary.","practice_takeaway":"Patient selection for PSMA-RLT should rely on PSMA PET imaging, disease burden assessment, and multidisciplinary team review. Clinicians should monitor for known toxicities and watch for evolving evidence supporting earlier use beyond heavily pretreated mCRPC."}},{"doi":"10.1038/s41391-026-01131-6","pmid":"42323390","title":"Efficacy and safety of darolutamide plus androgen-deprivation therapy in Black patients with metastatic hormone-sensitive prostate cancer from the phase 3 ARANOTE trial","journal_title":"Prostate Cancer and Prostatic Diseases","journal_issn":"1365-7852","published_at":"2026-06-20T00:00:00.000Z","url":"https://doi.org/10.1038/s41391-026-01131-6","source_score":9,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-24T13:21:37.952Z","updated_at":"2026-06-24T13:21:37.952Z","tags":[{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"brand","value":"Nubeqa","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"condition","value":"Metastatic Hormone-Sensitive Prostate Cancer","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"generic","value":"darolutamide","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"modality","value":"Androgen Deprivation Therapy","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"modality","value":"Androgen Receptor Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"sample_size","value":"n=65","value_numeric":65},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"study_design","value":"Subgroup Analysis of Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"warning","value":"Full safety data and secondary endpoints (e.g., overall survival, PSA response) were not reported in the available abstract text.","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"warning","value":"Level of evidence assigned as '2' reflects the RCT source trial; the subgroup analysis itself carries inherently lower certainty.","value_numeric":null},{"paper_doi":"10.1038/s41391-026-01131-6","tag_type":"warning","value":"This is a subgroup analysis of only 65 Black patients (10% of the total trial), so the 49% rPFS risk reduction should be interpreted with caution due to limited statistical power.","value_numeric":null}],"summaries":{"what_studied":"This pre-specified subgroup analysis of the phase 3 ARANOTE trial evaluated darolutamide 600 mg twice daily plus ADT vs. placebo plus ADT in Black patients (n=65) with metastatic hormone-sensitive prostate cancer.","key_result":"In Black patients, darolutamide + ADT reduced the risk of radiological progression or death by 49% vs. ADT alone (rPFS benefit), consistent with the overall ARANOTE population (N=669).","limitations":"Small subgroup (n=65; only 10% of total trial population), limiting statistical power. Safety data detail is sparse in the abstract. No overall survival or PSA response data reported in the available text.","practice_takeaway":"Darolutamide + ADT appears to offer meaningful rPFS benefit in Black patients with metastatic hormone-sensitive prostate cancer, a historically underrepresented group in clinical trials. Clinicians can apply these findings with cautious confidence given consistency with the overall trial result."}},{"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":"10.1097/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-24-02829","pmid":"41894648","title":"Radiographic Progression With and Without Prostate-Specific Antigen Rise in Patients With Advanced Prostate Cancer Treated With Enzalutamide","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-03-27T00:00:00.000Z","url":"https://doi.org/10.1200/jco-24-02829","source_score":41,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-08","doi":"10.1200/jco-24-02829","days":"7","issn":"0732-183X","rank":"4","field":"Clinical Medicine","score":"41","category":"Oncology","categories":["Oncology"],"_categories":["Oncology"]},"pubmed":{"doi":"10.1200/JCO-24-02829","title":"Radiographic Progression With and Without Prostate-Specific Antigen Rise in Patients With Advanced Prostate Cancer Treated With Enzalutamide.","journal":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology","methods":"","results":"In ARCHES, 3.5% and 8.5% of 574 patients with mHSPC treated with enzalutamide plus androgen-deprivation therapy (ADT) had no PSA rise or PSA progression at rPD, respectively. Of 79 patients with rPD who received enzalutamide plus ADT, 25.3% had no PSA rise and 62.0% did not meet PSA progression criteria compared with 7.4% and 38.3% of 188 patients with rPD treated with ADT alone, respectively. In PROSPER, 4.4% and 10.3% of 933 patients with nmCRPC treated with enzalutamide plus ADT had no PSA rise or PSA progression, respectively, at rPD. However, of 187 patients with rPD who received enzalutamide plus ADT, 21.9% had no PSA rise and 51.3% did not meet PSA progression criteria compared with 3.6% and 18.8% of 224 patients treated with placebo/ADT, respectively. Liver metastases were >5-fold higher in enzalutamide-treated patients with rPD events versus control, although sample size was small. Compared with no rPD, enzalutamide-treated patients with rPD ± PSA rise or progression had worse OS.","abstract":"$30","keywords":[],"pubmed_id":"41894648","conclusions":"Given the frequent discordance and poor prognosis of imaging-based progression in the absence of PSA changes during enzalutamide treatment in mHSPC and nmCRPC, periodic surveillance using imaging is recommended.","publication_date":"2026-03-27T00:00:00"},"crossref":{"DOI":"10.1200/jco-24-02829","URL":"https://doi.org/10.1200/jco-24-02829","ISSN":["0732-183X","1527-7755"],"link":[{"URL":"https://ascopubs.org/doi/pdfdirect/10.1200/JCO-24-02829","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"1309-1322","type":"journal-article","issue":"14","score":1,"title":["Radiographic Progression With and Without Prostate-Specific Antigen Rise in Patients With Advanced Prostate Cancer Treated With Enzalutamide"],"author":[{"given":"Andrew J.","family":"Armstrong","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Medical Oncology, Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, Durham, NC"}]},{"given":"Arun A.","family":"Azad","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia"},{"name":"Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia"}]},{"given":"Taro","family":"Iguchi","sequence":"additional","affiliation":[{"name":"Department of Urology, Kanazawa Medical University, Ishikawa, Japan"}]},{"given":"Arnulf","family":"Stenzl","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Tübingen, Tübingen, Germany"}]},{"given":"Nicolas","family":"Mottet","sequence":"additional","affiliation":[{"name":"Department of Urology, University Hospital, St Etienne, France"}]},{"given":"David","family":"Russell","sequence":"additional","affiliation":[{"name":"Pfizer Inc, New York, NY"}]},{"given":"Matt","family":"Rosales","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Northbrook, IL"}]},{"given":"Gabriel P.","family":"Haas","sequence":"additional","affiliation":[{"name":"Global Product Development, Astellas Pharma Inc, Northbrook, IL"}]},{"given":"Fred","family":"Saad","sequence":"additional","affiliation":[{"name":"University of Montreal Hospital Center, Montreal, QC, Canada"}]},{"given":"Maha","family":"Hussain","sequence":"additional","affiliation":[{"name":"Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL"}]},{"given":"Cora N.","family":"Sternberg","sequence":"additional","affiliation":[{"name":"Englander Institute for Precision Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, NY"}]}],"issued":{"date-parts":[[2026,5,10]]},"member":"233","prefix":"10.1200","source":"Crossref","volume":"44","created":{"date-time":"2026-03-27T19:59:07Z","timestamp":1774641547000,"date-parts":[[2026,3,27]]},"indexed":{"date-time":"2026-05-13T04:29:29Z","timestamp":1778646569019,"date-parts":[[2026,5,13]]},"subject":[],"abstract":"$31","language":"en","relation":{},"resource":{"primary":{"URL":"https://ascopubs.org/doi/10.1200/JCO-24-02829"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","order":0,"value":"2024-12-23"},{"name":"revised","group":{"name":"publication_history","label":"Publication 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Clinicians should use periodic imaging surveillance rather than relying solely on PSA trends to detect progression in mHSPC and nmCRPC."}},{"doi":"10.1158/1078-0432.ccr-25-3327","pmid":"41324555","title":"A Computational Pathology Model to Predict Docetaxel Benefit in Localized High-Risk and Metastatic Prostate Cancer","journal_title":"Clinical Cancer Research","journal_issn":"1078-0432","published_at":"2025-12-01T00:00:00.000Z","url":"https://doi.org/10.1158/1078-0432.ccr-25-3327","source_score":44,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-08","doi":"10.1158/1078-0432.ccr-25-3327","days":"7","issn":"1078-0432","rank":"10","field":"Clinical Medicine","score":"44","category":"Oncology","categories":["Oncology"],"_categories":["Oncology"]},"pubmed":{"doi":"10.1158/1078-0432.CCR-25-3327","title":"A Computational Pathology Model to Predict Docetaxel Benefit in Localized High-Risk and Metastatic Prostate Cancer.","journal":"Clinical cancer research : an official journal of the American Association for Cancer Research","methods":"","results":"In CHAARTED, APIC-positive patients (56.7%) showed significant overall survival improvement with docetaxel (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.31-0.85; P = 0.008) and delayed castration-resistance (HR 0.48, 95% CI 0.33-0.71; P < 0.001), while APIC-negative patients (43.3%) showed no benefit (HR 1.31, 95% CI 0.71-2.44; P = 0.39). Treatment-APIC interactions were significant (P = 0.022 and P = 0.031). In NRG/RTOG 0521, APIC-positive patients (44.7%) demonstrated survival benefit (HR 0.49, 95% CI 0.26-0.92; P = 0.023), while APIC-negative patients (55.3%) showed no benefit. Treatment-APIC interaction was significant (P = 0.024). Predictive value remained significant after adjusting for clinical variables. 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Cancer","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-3327","tag_type":"generic","value":"docetaxel","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-3327","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-3327","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-3327","tag_type":"modality","value":"Taxane Chemotherapy","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-3327","tag_type":"sample_size","value":"n=636","value_numeric":636},{"paper_doi":"10.1158/1078-0432.ccr-25-3327","tag_type":"study_design","value":"Retrospective Cohort","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-3327","tag_type":"warning","value":"Absolute survival rates and follow-up durations were not provided in the abstract.","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-3327","tag_type":"warning","value":"Design classification is approximate: this is a retrospective biomarker analysis of subsets from two phase 3 trials, not a randomized test of the classifier.","value_numeric":null},{"paper_doi":"10.1158/1078-0432.ccr-25-3327","tag_type":"warning","value":"Only subsets with available digitized biopsies were included, which may limit generalizability.","value_numeric":null}],"summaries":{"what_studied":"Retrospective analyses of two phase 3 trials (CHAARTED: 286/790 with mHSPC; NRG/RTOG 0521: 350/563 with high‑risk localized disease) evaluated an AI pathology image classifier (APIC) on H&E biopsies to predict which patients gain survival benefit from docetaxel using Cox models with treatment-by-APIC interaction.","key_result":"In CHAARTED, APIC‑positive patients (56.7%) had improved overall survival with docetaxel (HR 0.52, 95% CI 0.31–0.85; P=0.008) and delayed castration‑resistance (HR 0.48, 95% CI 0.33–0.71; P<0.001), while APIC‑negative patients (43.3%) did not (OS HR 1.31, 95% CI 0.71–2.44; P=0.39); treatment‑APIC interactions were significant (P=0.022 and P=0.031). In NRG/RTOG 0521, APIC‑positive patients (44.7%) showed an OS benefit (HR 0.49, 95% CI 0.26–0.92; P=0.023), APIC‑negative patients did not, and the interaction was significant (P=0.024); effects persisted after adjustment for clinical variables.","limitations":"Retrospective analysis; findings require prospective validation. Only subsets of trial participants with available digitized biopsies were analyzed (CHAARTED 286/790; NRG/RTOG 0521 350/563).","practice_takeaway":"APIC appears to identify which patients with mHSPC or high‑risk localized prostate cancer benefit from docetaxel, while others may not. Until prospectively validated, use is exploratory and should not replace current selection criteria."}}],"initialOffset":8,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Metastatic Hormone-Sensitive Prostate Cancer"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Metastatic Hormone-Sensitive Prostate Cancer"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Metastatic Hormone-Sensitive Prostate Cancer"}}}]]

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