Prostate Cancer and Prostatic Diseases最新文献

{"title":"Radical prostatectomy without prior biopsy: an initial decision-making algorithm based on PSMA PET/mpMRI","authors":"Zhuoran Li, Jin Luo, Qiwei Liu, Yuqi Jia, Zhiqiang Chen, Nanxin Zou, Jinqiao Li, Yujie Dong, Qiming Yang, Chao Wang, Zhuo Jia, Yundong Xuan, Xiaohui Ding, Honghao Xu, Baichuan Liu, Xixi Wang, Haiyi Wang, Yachao Liu, Xu Zhang, Weimin Ci, Shaoxi Niu, Songliang Du, Baojun Wang","doi":"10.1038/s41391-026-01081-z","DOIUrl":"10.1038/s41391-026-01081-z","url":null,"abstract":"Recent advancements in radiological imaging have raised the possibility of diagnosing prostate cancer (PCa) without biopsy; however, the safety, feasibility, and diagnostic accuracy of this approach require comprehensive evaluation. This study proposes and evaluates an initial decision-making algorithm using PSMA PET/CT and mpMRI for selecting candidates suitable for radical prostatectomy without prior biopsy (RP-WPB). Patient enrollment was conducted strictly according to the prospectively established decision-making algorithm. Candidates for RP-WPB were required to fulfill four essential criteria: PSA > 4 ng/mL, PI-RADS score≥4, miPSMA score≥2, and co-positive lesions identified on mpMRI and PSMA PET/CT. Patients staged as cT3-4, cN1, or cM1 (solitary metastasis) underwent RP-WPB directly. For patients with stage cT2N0M0, PSA levels were further stratified: those with PSA ranging from 4 to 30 ng/mL were invited to participate in the prospective study, whereas individuals with PSA ≥ 30 ng/mL qualified for RP-WPB only if they satisfied additional conditions, including age≥75 years, PSA density (PSAD) ≥ 0.2 ng/mL/cm3, and willingness to undergo non-neurovascular-bundle-sparing surgery. From January 2022 to February 2024, 150 patients were prospectively enrolled following the algorithm; 30 patients withdrew, and 120 underwent RP-WPB. Among the latter, 84 patients were classified as cT2N0M0, 27 as cT3-4, 10 as cN1, and 9 as cM1. The detection rate of clinically significant PCa (csPCa) (ISUP grade ≥2) patients was 100% (95% CI: 0.97-1.00, p = 0.176), and pathological concordance was achieved in all cases. No perioperative complications greater than Clavien-Dindo grade Ⅱ occurred. The proposed algorithm based on PSMA PET/CT and mpMRI for performing RP-WPB demonstrates safety, feasibility, and high diagnostic accuracy, presenting a promising option for selected PCa patients.","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":"29 3","pages":"625-632"},"PeriodicalIF":6.9,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of the new P100 extracorporeal shock wave therapy device in the treatment of type IIIB chronic prostatitis/chronic pelvic pain syndrome: a sham treatment controlled, prospective clinical trial","authors":"Haipeng Zhang, Wei Song, Jinliang Ni, Houliang Zhang, Ziming Jiang, Guangcan Yang, Yifan Zhang, Keyi Wang, Yifan Chen, Bo Peng","doi":"10.1038/s41391-026-01072-0","DOIUrl":"10.1038/s41391-026-01072-0","url":null,"abstract":"To evaluate the therapeutic efficacy and clinical applicability of the novel P100 extracorporeal shock wave therapy (ESWT) device in the treatment of type IIIB chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). In this randomized, single-blind, sham-controlled trial, 83 patients with type IIIB CP/CPPS were enrolled and randomly assigned to either the P100 treatment group (n = 51) or the control group (n = 32). Patients in the treatment group received four weekly low-intensity ESWT sessions (0.2 mJ/mm²), while the control group received identical procedures with shock transmission blocked. The primary endpoint was the clinical response rate (≥6-point reduction in NIH-CPSI score) at week 4; week 8 outcomes were further analyzed to assess sustained efficacy. Secondary endpoints included IPSS, IIEF-5, and VAS scores. At week 4, the clinical response rate was 78.4% in the P100 group compared with 25% in the control group (P < 0.001). Median NIH-CPSI scores decreased from 35 at baseline to 13 at week 4 and 12 at week 8, indicating sustained improvement. Significant reductions in PDS, IPSS, and VAS scores were observed as early as week 2 (P < 0.05), and symptom relief remained stable through week 8 without rebound. Exploratory analyses suggest that lower baseline estradiol levels and lower E2/T ratios may be associated with more sustained improvements in erectile function. No treatment-related adverse events were reported. The P100 ESWT device provided rapid, significant, and sustained symptom relief for type IIIB CP/CPPS, particularly in pain and urinary domains. Hormonal balance (E2/T) may influence the long-term maintenance of erectile function after ESWT. These findings support P100 as a safe and effective non-invasive therapeutic option for CP/CPPS, warranting further validation in larger studies with longer-term follow-up.","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":"29 4","pages":"781-790"},"PeriodicalIF":6.9,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146066478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of bone fractures in patients with prostate cancer treated with maximal androgen blockade therapy: a systematic literature review and meta-analysis","authors":"Isabella Saporita, Mariangela Calabrese, Federica Maria Carfi, Andrea Mogavero, Marialuisa Puglisi, Giorgio Treglia, Ursula Maria Vogl, Silke Gillessen, Ricardo Pereira Mestre, Martino Pedrani, Giovanna Pecoraro, Giuseppe Salfi, Caroline-Claudia Erhart, Hui-Ming Lin, Luigi Tortola, Massimo Di Maio, Marcello Tucci, Consuelo Buttigliero, Fabio Turco","doi":"10.1038/s41391-026-01077-9","DOIUrl":"10.1038/s41391-026-01077-9","url":null,"abstract":"Addition of an androgen receptor pathway inhibitor (ARPI) to androgen deprivation therapy (ADT) (ADT + ARPI, i.e., maximal androgen blockade, MAB) improves survival outcomes compared to ADT monotherapy in patients with prostate cancer (PC). It is known that ADT increases the risk of fractures in patients with PC, but it is unclear if this risk is higher with MAB. The aim of this study is to conduct a systematic review and meta-analysis to determine if MAB increases the incidence of fractures compared to ADT alone, and if the incidence of fractures was influenced by the type of ARPI. Clinical trials assessing MAB versus ADT alone in patients with PC were identified using the PubMed/Medline and Cochrane library databases. The pooled odds ratio of developing fractures with MAB versus ADT alone was calculated for each type of ARPI in selected studies by random-effects modeling. The number of patients receiving bone-protecting agent (BPA) was also evaluated. We identified 17 studies comprising 16162 patients for the systematic review and meta-analysis (9240 patients treated with MAB, 6922 patients treated with ADT alone). Each type of ADT + ARPI resulted in a statistically significant increased risk of fractures compared to ADT alone (pooled OR ranging from 1.5 to 2.4). There was no difference in the magnitude of the risk of fractures among the different ARPIs. Only 7 studies reported the number of patients treated with a BPA. In our meta-analysis, MAB resulted in a statistically significant increase in fracture risk compared to ADT alone, regardless of the type of ARPI. Since long-term MAB represents the standard of care in various settings of PC, the use of a BPA should be generally recommended. Dosing and frequency of BPA need to be adapted according to the specific PC setting.","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":"29 4","pages":"669-677"},"PeriodicalIF":6.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The value of micro-ultrasound for prostate cancer screening: A retrospective real-world feasibility study","authors":"Johann Jakob Wendler, Jonas Bechstein, John Buckendahl, Stephan Kruck, Christian Samtleben, Bernd Uwe Liehr, Markus Porsch, Hannes Cash","doi":"10.1038/s41391-026-01075-x","DOIUrl":"10.1038/s41391-026-01075-x","url":null,"abstract":"Prostate cancer (PCa) screening is increasingly guided by imaging. High-resolution 29 MHz Micro-Ultrasound (MUS) offers a promising alternative to magnetic resonance imaging (MRI). We retrospectively analyzed 682 consecutive men undergoing MUS and PSA testing during routine examination. Biopsy and MRI were performed according to guideline recommendations. PSA density (PSAD)-modified negative MUS included PRI-MUS categories 1, 2, or 3 with PSAD < 0.15 ng/mL2; PSAD-modified positive MUS included PRI-MUS categories 3 with PSAD ≥ 0.15 ng/mL2, 4 or 5. Median age was 59 years; median PSA 1.2 ng/mL (IQR: 0.6–3.5). Biopsies were performed in 62 men, detecting PCa in 29 (47%), including 18 (29%) clinically significant PCa (csPCa). 88 men (13%) had PSAD-modified positive MUS, yielding 15 csPCa and 7 non-clinically significant PCa (ncsPCa). Among 594 men (87%) with PSAD-modified negative MUS, 3 csPCa and 4 ncsPCa were detected. Compared to PSA-based biopsy indication ≥3 ng/mL, PSAD-modified negative MUS would have avoided 13 negative, missing two csPCa and four ncsPCa. Compared to the MRI-based biopsy indication (PI-RADS ≥ 3, n = 38), PSAD-modified negative MUS (n = 594) would have spared 3 negative biopsies, as well as 17 (24.7% of 69) MRIs due to negative biopsy, while missing 0 cases of csPCa. Additionally, MRI could have been omitted in 1csPCa case and 9 ncsPCa cases with positive MUS, and in 13 csPCa and 7 ncsPCa cases based on PSAD-modified positive MUS. The PSAD-modified-PRI-MUS-based screening pathway showed a 6.29-fold (OR = 0.16) reduction in overdiagnosis and 7.22-fold (OR = 0.14) reduction in negative biopsies/ncsPCa. MUS without PSA demonstrated an OR of 7.30 to detect csPCa. PSAD-modified-PRI-MUS score demonstrated a sensitivity of 83.3%, a specificity of 59.1%, a positive predictive value of 45.5% and a negative predictive value of 89.7% for distinguishing csPCa from benign/ncsPCa findings. MUS enables effective PCa risk stratification in an opportunistic screening setting supporting prospective trial development. This study is part of the PROSTAMUS trial, registered in the DRKS/WHO registry.","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":"29 4","pages":"799-805"},"PeriodicalIF":6.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41391-026-01075-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"5 T versus 3 T MRI for prostate cancer: an intra-individual prospective comparison of image quality and diagnostic performance","authors":"Tianyu Xiong, Liting Shen, Yunpeng Fan, Mingxin Jiang, Liang Wang, Dan Yu, Zhenghan Yang, Yinong Niu","doi":"10.1038/s41391-026-01073-z","DOIUrl":"10.1038/s41391-026-01073-z","url":null,"abstract":"To prospectively compare the image quality and diagnostic performance of ultra-high-field 5 T MRI with that of standard 3 T in patients with suspected prostate cancer (PCa). Sixty-seven consecutive patients received prostate scan at both 5 T and 3 T MRI systems. Two radiologists independently evaluated the images in a double-blind manner. A head-to-head comparison of 5 T and 3 T MRI was conducted from both qualitative and quantitative perspectives. Pathological results from prostate biopsy and radical prostatectomy were used as the gold standard to evaluate the diagnostic performance. 5 T MRI demonstrated superior image quality and enhanced visualization of prostatic anatomical structures, including prostatic capsule, seminal vesicle and neurovascular bundles. The lesion delineation was significantly improved in 5 T MRI. The elevated field strength resulted in a significantly higher signal-to-noise ratio, contrast-to-noise ratio, edge rise distance and lesion slope profile in both T2WI and DWI sequences without introducing additional artifacts. Moreover, 5 T MRI demonstrated improved diagnostic performance for biopsy outcomes and pathological features than 3 T. 5 T MRI effectively improves PCa assessment compared to 3 T. Our study provides preliminary evidence for the feasibility of 5 T MRI in PCa diagnosis and evaluation.","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":"29 3","pages":"617-624"},"PeriodicalIF":6.9,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzalutamide in metastatic hormone-sensitive prostate cancer: results from the international, multicentre, real-world ARON-3 study","authors":"Thomas Büttner, Mimma Rizzo, Laura Bernal Vaca, Javier Molina-Cerrillo, Teresa Alonso-Gordoa, Alvaro Juárez, Tomas Buchler, Emmanuel Seront, Jakub Kucharz, María Natalia Gandur Quiroga, Maria T. Bourlon, Martin Bögemann, Jindrich Kopecky, Pasquale Rescigno, Ondrej Fiala, Alejo Rodriguez-Vida, Zin W. Myint, Yüksel Ürün, Sarah Scagliarini, Alexandr Poprach, Diana Matthews, Haoran Li, Alessandro Rizzo, Alessandra Mosca, Edoardo Lenci, Bohuslav Melichar, Mike Wenzel, Philipp Mandell, Francesco Massari, Emmanuel S. Antonarakis, Matteo Santoni","doi":"10.1038/s41391-025-01067-3","DOIUrl":"10.1038/s41391-025-01067-3","url":null,"abstract":"Enzalutamide (ENZA), a next-generation non-steroidal androgen receptor (AR) inhibitor, plays a pivotal role in the management of both hormone-sensitive (HSPC) and androgen deprivation-resistant prostate cancer (ARPC). This paper presents real-world clinical outcomes of ENZA in a subgroup of metastatic HSPC (mHSPC) patients included in the ARON-3 study. Clinical information was extracted retrospectively from medical records at 29 cancer centres in 9 countries worldwide. Overall Survival (OS) was calculated from starting ENZA to death from any cause and the time on treatment (ToT) from ENZA initiation to discontinuation for any reason. The Kaplan–Meier method was used to estimate OS and ToT. PSA90 was defined as a ≥90% PSA reduction from baseline, and PSA0.2 as the achievement of an ultra-low PSA level ≤0.2 ng/ml. Adverse events (AEs) were categorised according to Common Terminology Criteria for Adverse Events v5.0. The study population comprised 424 patients treated with ENZA for mHSPC, of whom 80 (19%) had lymph node-only metastases, 265 (63%) bone-only metastases, and 50 (12%) visceral metastases. 273 patients (64%) had synchronous metastases and 151 (36%) had developed metachronous metastases. A total of 228 patients were diagnosed with low-volume disease, and 196 patients (46%) with high-volume disease. The median ToT was 31.8 months, and the median OS was not reached. The median time to PSA90 (achieved in 76% of patients) and PSA0.2 (59% of patients) was 6.0 months and 8.3 months, respectively. Statistically significant associations were identified between lymph node-only patterns, PSA90 and ultra-low PSA responses, and longer treatment duration and better overall survival. Grade 3–4 AEs were observed in 9% of patients <70 years and in 10% ≥70 years. Real-world clinical practice corroborates the findings from clinical trials, confirming the effectiveness and safety of ENZA in mHSPC patients.","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":"29 3","pages":"588-594"},"PeriodicalIF":6.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41391-025-01067-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of the Prostatype® P-score for predicting prostate cancer specific mortality in a multiethnic U.S. veterans cohort","authors":"Alexandra Mack, Trung Duong Tran, Emelie Berglund, Gerald L. Andriole, Christopher Alley, Anthony E. Sisk, Iveth Estrada-Reyes, Kara Bissell, Haleigh Bellerose, Aubrey Jarman, Anna Hoffmeyer, Michael Burns, Sergio Sanders, Eric Vail, Andy Pao, Raja Khurram, Amal Ahmed, Stephen J. Freedland","doi":"10.1038/s41391-025-01070-8","DOIUrl":"10.1038/s41391-025-01070-8","url":null,"abstract":"The Prostatype® Test evaluates expression levels of three stem cell genes (IGFBP3, F3, and VGLL3), which are combined with PSA, stage, and grade to calculate P-score. Previous research found P-score accurately predicts prostate cancer (PC) specific mortality (PCSM) in patients with newly diagnosed clinically localized PC. We evaluated the performance of P-score to predict PCSM in a large, multiethnic cohort from the Veterans’ Administration (VA). After pathologic review to ensure sufficient tumor tissue, formalin-fixed paraffin-embedded (FFPE) biopsy cores from patients with newly diagnosed PC at the Durham VA were sent to an academic medical center. There, cores were sectioned, RNA extracted, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) tests conducted for IGFBP3, F3, VGLL3, and GAPDH (control). Results were combined with clinical data to generate P-scores. The association between P-score and PCSM was evaluated using c-index, Cox and Fine-Gray models, and decision curve analysis (DCA). Higher P-scores were significantly associated with a higher risk of PCSM (HR = 1.48 per 1 unit increase in P-score, 95% CI: 1.20–1.84, p <0.001) and accurately estimated PCSM (c-index = 0.87). Adding clinical variables to P-score only incrementally improved accuracy. The DCA indicated P-score provided net clinical benefit for patients with PCSM risk between 5% and ~50%. As P-score strongly correlated with risk group, we tested the value of P-score in intermediate-risk patients specifically, where it significantly predicted PCSM (HR 1.43, 95% CI: 1.09–1.86, p = 0.009). In this American cohort of veterans, P-score significantly predicted PCSM. Adding clinical variables minimally improved accuracy. Accuracy remained high in intermediate-risk patients, wherein there is arguably the greatest need for better risk stratification. Given P-scores can be generated rapidly in-house using a standardized RT-qPCR assay, P-score represents a robust new tool to risk-stratify newly diagnosed patients for PC death, thereby minimizing mismatched treatments.","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":"29 3","pages":"611-616"},"PeriodicalIF":6.9,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41391-025-01070-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant pamiparib plus abiraterone and androgen deprivation therapy for high-risk/very high-risk localized prostate cancer: an open-label, single-arm, phase 2 study","authors":"Tangtao Gong, Shuo Liang, Zhigang Wu, Xuefeng Qiu, Linfeng Xu, Shan Peng, Hongqian Guo, Shun Zhang, Junlong Zhuang","doi":"10.1038/s41391-025-01068-2","DOIUrl":"10.1038/s41391-025-01068-2","url":null,"abstract":"Androgen receptor signaling inhibition (ARPI) increases genomic instability of double-stranded DNA breaks, and co-inhibition of androgen receptor (AR) and poly(ADP-ribose) polymerase (PARP) induces synthetic lethality in multiple preclinical models. This phase II study evaluated the efficacy, safety, and quality-of-life (QoL) impact of neoadjuvant pamiparib plus abiraterone and androgen deprivation therapy (ADT) in patients with high-risk or very high-risk localized prostate cancer (HRPCa/VHRPCa). In this single-arm trial, patients with HRPCa/VHRPCa, defined as Gleason score ≥8, and/or cT3–4N0–1, and/or PSA ≥ 20 ng/mL, received pamiparib plus abiraterone and ADT for 4 months before radical prostatectomy (RP). The primary endpoint was pathological complete response (pCR; no residual tumor) or minimal residual disease (MRD; ≤5 mm residual tumor). Secondary endpoints included PSA response, surgical downstaging, 2-year biochemical progression-free survival (bPFS), QoL metrics, and safety. Thirty patients were enrolled; 29 completed therapy and underwent RP. Median age was 65 years, and 9 patients had enlarged pelvic lymph nodes. Homologous recombination repair (HRR) mutations were detected in 7 patients. Overall, 8 patients (28%) achieved pCR or MRD (pCR in 3 [10%], MRD in 5 [17%]), and 18 patients (62%) had surgical downstaging, with no progression events. No significant difference in pCR or MRD rates was observed between patients with HRR mutations and those without HRR mutations. Two-year bPFS was 76%. FACT-P scores improved in 18 patients (62%) during therapy, with 9 of 22 (41%) maintaining improvement postoperatively. At 12 months, mean EPIC-26 urinary incontinence score was 83.2 ± 12.5. No grade 3–4 treatment-related adverse events occurred; common grade 1–2 events were anemia (45%), elevated AST/ALT (34%), and hypertriglyceridemia (45%). Neoadjuvant pamiparib plus abiraterone and ADT demonstrated efficacy, safety, and potential QoL benefits in HRPCa/VHRPCa.","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":"29 3","pages":"595-601"},"PeriodicalIF":6.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial immune profiling of bone-metastatic castration-resistant prostate cancer reveals radium-223 immunomodulates the bone-tumor microenvironment","authors":"Paul G. Corn, Guoyu Yu, Yibo Fan, Miao Zhang, Patricia Troncoso, Devaki Shilpa Surasi, Suyu Liu, Jaffer A. Ajani, Christopher J. Logothetis, Guocan Wang, Theocharis Panaretakis, Sue-Hwa Lin","doi":"10.1038/s41391-025-01069-1","DOIUrl":"10.1038/s41391-025-01069-1","url":null,"abstract":"Prostate cancer (PCa) bone lesions are bone-forming, which contribute to an immunosuppressive bone-tumor microenvironment (bone-TME). Targeting PCa-induced bone with the radiopharmaceutical Radium-223 (Ra223) is approved for men with bone-metastatic castration-resistant PCa (bmCRPC). We studied the effect of Ra223 on spatial localization of tumor and immune cells in bmCRPC tumor biopsies to gain insights into therapeutic immunomodulation of the bone-TME. Transiliac bone marrow biopsies were performed at baseline and end of treatment (EOT) in 24 patients with bmCRPC treated with Ra223. In three patients with paired specimens containing tumor, multiplex immunofluorescence was performed with antibodies for a tumor cell marker (CK), T-cell markers (CD3, CD4, CD8, FOXP3, and granzyme B), macrophage markers (CD68 [total macrophages] and CD206 [M2-like macrophages]). In all three patients, we observed enrichment of CD68+ macrophages, around tumor-induced bone at baseline. CD3 staining revealed T cell depletion where tumor cells formed large sheets but not where tumor cells were scattered. The effects of Ra223 on tumor cells and T cell subsets were heterogeneous. In one patient, tumor cells were reduced, and CD3+/CD8+ T cells were increased. In a second patient who evidenced osteolytic progression, tumor cells were increased while CD3+/CD8+ T cells were decreased. In a third patient, there was high number of tumor cells at baseline that modestly decreased and the number of CD3+/CD8+ T cells modestly increased after Ra223 treatment. The changes in tumor cell numbers after Ra223 treatment seemed to be inversely correlated with changes in CD3+/CD8+ and CD4+/FoxP3+ cells, but not with other immune cells, in these 3 patients. Further characterization of immune cells in the bone-TME will be required before developing strategies to enhance immunotherapy efficacy in bmCRPC. This study does not report the clinical results of a clinical trial, but it does use samples from a completed clinical trial that is registered with clinicaltrials.gov (NCT02135484).","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":"29 3","pages":"602-610"},"PeriodicalIF":6.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41391-025-01069-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic profiling of tumor-associated antigen expression for antibody-drug conjugate in prostate cancer","authors":"Yelin Mulati, Qi Shen, Yuke Chen, Yuxuan Tian, Kaifeng Yao, Wei Yu, Yunpeng Cui, Xuedong Shi, Xiaocong Pang, Dongyuan Chang, Zhisong He, Xinan Sheng, Qian Zhang, Yu Fan","doi":"10.1038/s41391-025-01066-4","DOIUrl":"10.1038/s41391-025-01066-4","url":null,"abstract":"The aim of this study is to better characterize the expression profiles of well-established tumor-associated antigen (TAA) for antibody-drug conjugates (ADC) in primary lesion (PL) and bone metastatic lesion(BML) of prostate cancer (PCa). Mass spectrometry (MS) and immunohistochemistry (IHC) were used to comprehensively compare the expression of HER2, NECTIN4, TROP2, PSMA, TF, STEAP1 and B7H3 in the matched cohort (n = 27 pairs), which included matched PL and BML samples from the same patients. IHC was then used to validate the expression of these TAAs in another independent unmatched cohort, including PL (n = 100) and BML (n = 49). IHC assessment included traditional semi-quantitative evaluation, computer-assisted H-score assessment and normalized membrane ratio (NMR) analysis. B7H3, STEAP1 and PSMA consistently exhibited high and stable expression rate in matched PL and BML, whereas the expression levels of the other TAAs may fluctuate between the two status. In the unmatched cohort, the expression levels of TROP2, TF, PSMA, and B7H3 were significantly lower, while the expression levels of HER2 and STEAP1 were significantly higher in BML than in PL (all p < 0.05). Overall, STEAP1, B7H3 and PSMA exhibited high expression rates in BML, with STEAP1 and B7H3 depicting relatively homogeneous high membranous expression patterns. The co-expression of these TAAs was frequently observed. In the dual-TAA combination analysis, any pairwise combination among B7H3, STEAP1, and PSMA exhibited relatively high expression coverage(å 85%) for BML. B7H3, STEAP1, and PSMA might be the predominant targets in both PL and BML. Our findings reveal the dynamic and heterogeneous nature of TAA expression in PCa and may provide insights for integrating ADC-based targeted therapies into the existing treatment landscape for PCa.","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":"29 3","pages":"578-587"},"PeriodicalIF":6.9,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}