Prostate Cancer and Prostatic Diseases最新文献

Background: 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.

Methods: 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.

Results: 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.

Conclusions: Real-world clinical practice corroborates the findings from clinical trials, confirming the effectiveness and safety of ENZA in mHSPC patients.

Background: 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).

Methods: 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).

Results: 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).

Conclusion: 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.

Background: 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).

Methods: 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.

Results: 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%).

Conclusions: Neoadjuvant pamiparib plus abiraterone and ADT demonstrated efficacy, safety, and potential QoL benefits in HRPCa/VHRPCa.

Background: 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.

Methods: 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]).

Results: 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.

Conclusions: 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.

Clinical trial registration: 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).

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Background: The technical advances allowed to take the leap towards hypofractionated schedules, as well as dose-escalated schedules, for prostate cancer (PCa) radiotherapy (RT). The aim of this systematic review is to describe RT techniques and toxicity outcomes within trials investigating hypofractionation, and to discuss current or future strategies to mitigate treatment-related toxicity.

Methods: We searched Pubmed database until June, 2025. Studies deemed eligible were phase III trials randomizing different type of fractionation (with at least one arm using hypofractionation) for PCa RT.

Results: Thirty-two articles were included. Rates of late grade≥2 genitourinary (GU) toxicity ranged between 12-46% and 15-45% for patients receiving isodose and dose-escalated moderately hypofractionated radiotherapy (MHRT). A flare of grade≥2 GU toxicity was observed 12 to 24 months following stereotactic body radiotherapy (SBRT), translating into a higher cumulative incidence of grade≥2 GU toxicity at 5 years. Higher IPSS at baseline was suggested to be predictive of late grade≥2 GU toxicity following both MHRT and SBRT. Overall, MHRT does not seem to negatively impact late gastrointestinal (GI) toxicity, with rates of late grade≥2 toxicity ranging between 8.9-25% and 12.7-23.8% for isodose and dose-escalated MHRT. Current mitigation strategies include minimizing the dose delivered to organs at risk (OARs), prolonging overall treatment time, and personalizing treatments based on individual radiosensitivity. Among the strategies allowing for a reduction of the dose to adjacent OARs, margin reduction achieved through motion management strategies halved the rates of grade≥2 toxicity following PCa SBRT.

Conclusions: Grade≥2 GU toxicity remains frequent in trials testing hypofractionation. Mitigation strategies are therefore critical to the continued evolution of intensified RT regimens. Motion management and margin reduction are particularly promising approaches to reduce severe toxicity after PCa SBRT, warranting their incorporation into clinical practice and future clinical trial designs.

Background: Recent advancements in artificial intelligence (AI) hold great promise in oncology, including prostate cancer care. Despite its promises, there is a lack of comprehensive synthesis and knowledge regarding the efficacy of the current AI-based prostate cancer tools. This study aims to identify, evaluate and synthesize the existing evidence on AI-based tools developed for the diagnosis, prognosis, and management of prostate cancer.

Method: We performed a systematic review of published studies from January 2020 to April 2025 that were retrieved from PubMed, Scopus, and Clinical Trials.gov focusing on the AI-based tools that are used in the diagnosis and management of prostate cancer care. Two independent reviewers utilized the PRISMA 2020 guidelines, develop a data charter and synthesize the study data using Covidence Software along with QUADAS-AI tool to assess paper quality and evaluate risk of bias. Meta-analysis was conducted on synthesized data using R.

Results: 43 studies were included, mostly retrospective and diagnostic-focused (n = 29), with deep learning being the most common AI model (49%). A meta-analysis of 34 studies with random effects pooled performance on AUC for the diagnostic tools (k = 27, MD = 0.845, 95% CI: 0.809,0.881), while prognostic tools (k = 7, MD = 0.785, 95% CI: 0.715, 0.856), with subgroup analysis indicating deep learning models (k = 17, MD = 0.854, 95% CI: 0.808, 0.901) out performed classical models (XGBoost, SVM, RF; k = 14, MD = 0.805, 95% CI: 0.756, 0.856). Seven narrative studies highlighted the emerging LLM role, and quality assessment revealed a low risk of bias, though concerns remained on the applicability of tools due to the validation method.

Conclusion: This review highlights the promising AI tool performance for prostate cancer care continuum, while concerns on pool performances and real-world applicability. Future studies should emphasize human-centric design with equity-focused evaluations to ensure robust, ethical, scalable AI deployments in prostate cancer care.

Background: For de-novo oligometastatic prostate cancer (omHSPC) treated with standard of care androgen suppression and prostate radiotherapy, the patterns of progression vis-a-vis index metastatic sites are not well understood.

Methods: This single-centre study included patients with de-novo omHSPC (CHAARTED criteria) staged with a PSMA-PET/CT scan at diagnosis, treated with systemic therapy and prostate radiotherapy, and re-staged with PSMA-PET/CT at biochemical progression. Disease status at index oligometastases was noted at progression.

Results: From 2015 to 2024, 79 patients with omHSPC were found eligible (M1a = 22, M1b = 57). Over a median follow-up of 39 months (IQR 28-69), 15 patients (19%) had disease progression. Restaging PSMA-PET/CT revealed progression of the index oligometastases for 11/15 patients (73%), with additional metastases in 7 of these.

Conclusion: The high proportion of progression at the index oligometastases supports the potential benefit of metastasis-directed therapy for local ablation.