Prostate最新文献

Background: Combined inhibition of AKT and the androgen receptor (AR) might be more efficacious than AR inhibition alone in biochemical recurrence (BCR) of prostate cancer (PC) by additive effects on the two effector pathways.

Patients and methods: E2809 assigned 108 high-risk BCR patients (1:1, arm-A: arm-B) to two phases with 4-week cycles: first (PreBic) phase (3 cycles), arm-B received AKT inhibitor MK-2206 200 mg 2x/week, arm-A was observation; second phase, bicalutamide (Bic), 50 mg daily, was added to each arm. The PreBic phase assessed whether AKT inhibition changed PSA, reflecting AR activation. Exploratory primary endpoint (EP1) at 6-8 Bic cycles and secondary EP2 at cycle 14 compared the proportion of cases with ≥stable disease (SD) or progressive disease (PD).

Results: PreBic phase: 70% arm-B vs 32% arm-A patients had a ≥ 60% PSA rise (p = 0.02). MK-2206 skin toxicity (38% grade ≥ 3) drove high withdrawal prior to EP1. Bic phase: at EP1, inter-arm PSA response (81%/82%) or PD (19%/18%) was equal. At EP2, PD was greater in arm-A than arm B (36% vs 11%; p = 0.04). In subgroups defined by PreBic phase PD (PBPD; PSA rise ≥ 25%), 9/16 arm-A vs 0/7 arm-B cases experienced PD at EP2 (p = 0.02); overall between PBPD-subgroups, 73% arm-A vs 27% arm-B experienced PD.

Conclusions: The results suggest that latent improved outcome of high-risk BCR patients (mean PSA doubling time 4.4 months) on combined MK-2206+Bic versus Bic alone was attributable to a subgroup identified by crosstalk AR activation secondary to inhibition of AKT. Toxicity may affect tolerance of sustained AKT-AR inhibition.

Clinical trial registration: ClinicalTrials. gov number, NCT01251861.

Backgrounds: The sign of Leser-Trélat (SLT) is defined by the abrupt onset of multiple pruritic or nonpruritic seborrhoeic keratoses (SKs) over a short interval, predominantly affecting the back, and is most frequently associated with internal malignant neoplasia, particularly gastric and colorectal adenocarcinoma.

Case presentation: We report a rare case of a 65-year-old male with SLT in association with prostate adenocarcinoma.

Conclusions: This report underscores the importance of including prostate assessment in the diagnostic work-up of men with rapidly evolving, multiple, and progressive SKs.

Background: In prostate cancer (PCa), smoking history is associated with more aggressive clinicopathological features, reduced efficacy of androgen deprivation therapy, and poorer overall survival (OS). However, its impact on survival outcomes in patients receiving taxane chemotherapy, poly ADP-ribose polymerase inhibitor (PARPi), or immune checkpoint inhibitor (ICI) therapy for PCa remains unclear. We compared the genetic profiles of smokers and non-smokers with PCa in several public databases to explore the potential influence of smoking on treatment outcomes.

Methods: We retrospectively collected data on smoking history, tumor characteristics, genomic information, treatment history, and survival outcomes from three public databases to investigate the role of smoking in PCa. Patients were categorized into smokers and non-smokers, and associations between smoking history and clinicopathological features, genetic profiles, and treatment outcomes were analyzed. Independent risk factors for OS were evaluated using multivariate Cox proportional hazard regression models.

Results: Smokers exhibited significantly higher Gleason score, clinical stage, tumor mutational burden, fraction genome altered, and microsatellite instability scores than non-smokers. The survival analysis revealed that smokers had significantly poorer OS than non-smokers in the overall, hormone therapy, and PARPi therapy cohorts. In contrast, no significant difference in OS was observed between the taxane chemotherapy and ICI therapy cohorts. Furthermore, multivariate Cox proportional hazard regression analysis identified smoking history as an independent risk factor for OS in the overall, hormone therapy, and PARPi therapy cohorts. Oncoplot analysis showed a significantly higher frequency of TP53 mutations and PTEN copy number alterations in smokers than in non-smokers.

Conclusions: Smoking history was significantly associated with aggressive clinicopathological features and a poor prognosis in patients with PCa. Our findings suggest that smokers with PCa may receive greater benefit from the early administration of taxane chemotherapy in comparison to other treatment regimens.

Background: Pathological upgrading after surgery is common among men with biopsy Gleason score (GS) 3 + 3 prostate cancer who undergo radical prostatectomy and may impact prognosis, highlighting the need for preoperative risk identification. This study aimed to develop and internally validate a predictive nomogram for pathological upgrading in this surgically treated population.

Methods: Patients aged ≥ 18 years with biopsy GS 3 + 3 prostate adenocarcinoma who underwent radical prostatectomy between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. A total of 14,484 patients were included and randomly divided into a training cohort and a validation cohort in a 7:3 ratio. Multivariable logistic regression was used to construct a prediction model based on preoperative clinical variables. Model performance was assessed using discrimination, calibration, and decision curve analysis. Internal validation was performed using bootstrap resampling and 10-fold cross-validation. Survival differences between risk groups defined by the nomogram were evaluated using Kaplan-Meier analysis.

Results: Overall, 47.9% of patients experienced pathological upgrading to a radical prostatectomy GS of 3 + 4 or higher. Age, prostate-specific antigen (PSA) level, number of positive biopsy cores, and clinical T stage were independently associated with upgrading and were incorporated into the final nomogram. The model demonstrated moderate discrimination, with an area under the curve (AUC) of 0.663 (95% CI, 0.652-0.673) in the training cohort and 0.648 (95% CI, 0.632-0.664) in the validation cohort. Bootstrap internal validation yielded an optimism-corrected C-statistic of 0.662. Calibration was satisfactory, and Brier scores were 0.228 in the training cohort and 0.231 in the validation cohort. In exploratory, unadjusted analyses, patients classified as high risk by the nomogram had significantly lower overall survival than those in the low-risk group.

Conclusions: The nomogram demonstrated moderate predictive performance for pathological upgrading in men with biopsy GS 3 + 3 prostate cancer who were selected for radical prostatectomy, and may assist in individualized preoperative decision-making within this surgical population.

Background: Prostate cancer (PCa) is the most common malignant tumor in men, but the widely used prostate-specific antigen (PSA) test has limited diagnostic accuracy. Research proposes that the loss of the Y chromosome (LOY) may affect the occurrence and development of prostate cancer, aiming to assess its potential as a diagnostic biomarker to improve the accuracy of prostate cancer detection and clinical management.

Methods: LOY levels were measured using droplet digital polymerase chain reaction (ddPCR) method, integrating relevant clinical indicators to evaluate the potential clinical significance of LOY in PCa. Logistic regression was employed to estimate risk prediction capability of LOY, and model performance was validated through bootstrapping.

Findings: 131 men patients were enrolled in this study whose PSA level exceeding 4.0 ng/ml and underwent prostate biopsies. According to post-biopsy pathological results, subjects were classified into normal and cancer groups. LOY levels were significantly higher in the cancer group than in the normal group (p < 0.001). LOY levels show a consistent increase with advancing AJCC clinical stage and escalating PI-RADS scores. LOY is a promising biomarker for PCa (AUC = 0.898). Clinical decision curve analyzes demonstrated that incorporating LOY into each conventional model provided greater clinical benefit compared with the original model.

Interpretation: In biopsy patients, the LOY levels in the cancer group were higher than those in the normal group, and this was more pronounced in patients at advanced clinical stages. LOY levels have strong diagnostic efficacy for PCa, indicating that LOY may serve as an auxiliary biomarker for early PCa diagnosis.

Background: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is increasingly used for pelvic nodal staging in prostate cancer and is often incorporated into radiotherapy decision-making. However, the negative predictive value of PSMA PET/CT for microscopic nodal disease remains imperfect. This study aimed to determine the true rate of occult pelvic lymph node metastases in patients with negative PSMA PET/CT using surgical histopathology as the reference standard.

Methods: This retrospective surgical validation study included 51 patients with intermediate- or high/very high-risk prostate cancer and negative pelvic lymph node findings on preoperative ⁶⁸Ga-PSMA PET/CT. All patients underwent radical prostatectomy with extended pelvic lymph node dissection between January 2021 and December 2024. Histopathological lymph node status (pN) served as the primary outcome. Clinical, imaging, and pathological variables were analyzed for associations with occult nodal metastases.

Results: Despite negative PSMA PET/CT findings, 6 of 51 patients (11.8%) had histopathologically confirmed pelvic lymph node metastases. Patients with pN+ disease were significantly older (median: 70 vs. 64 years, p = 0.019) and had higher preoperative PSA levels (mean: 24.85 vs. 12.95 ng/mL, p = 0.006). pN+ status was also associated with higher preoperative nodal risk scores. No significant differences were observed for Gleason grade group, clinical T stage, lymphovascular invasion, perineural invasion, or cribriform morphology between pN+ and pN- groups.

Conclusion: Negative PSMA PET/CT does not reliably exclude microscopic pelvic lymph node metastases in intermediate- and high/very high-risk prostate cancer. These findings demonstrate a biologically relevant false-negative rate for PSMA-based nodal staging. While this study does not assess radiotherapy outcomes, the presence of occult nodal disease in PSMA-negative patients supports a cautious, risk-adapted approach to treatment de-escalation strategies involving pelvic nodal irradiation.

Background: Long-term clinical data evaluating oncological outcomes and patient-reported quality of life (QOL) after combining celecoxib with radiotherapy are lacking. Therefore, we aimed to assess oncological outcomes and QOL with extended follow-up to determine the effect of celecoxib combined with low-dose-rate brachytherapy (LDR-BT) in the present study.

Patients and methods: An open-label, randomized study was conducted to evaluate the effect of COX-2 inhibitors, specifically celecoxib, on preventing acute genitourinary system toxicity between May 2010 and July 2013, with a negative result for the primary endpoint. In the control group (n = 156), tamsulosin was administered at 0.2 mg/day for 6 months, and in the celecoxib group (n = 154), tamsulosin at 0.2 mg/day for 6 months was combined with celecoxib at 200 mg/day for 3 months. Oncological outcomes and QOL (Expanded Prostate Cancer Index Composite) were compared between the two groups in this post hoc extended follow-up analysis.

Results: The median follow-up time after LDR-BT was 120 months (interquartile range, 98-134 months). The cumulative incidences of biochemical recurrence (BCR) and metastasis were significantly lower in the celecoxib group than those in the control group (10-year cumulative incidence of BCR: 1.5% vs 9.0%, p = 0.006; 10-year cumulative incidence of metastasis: 0% vs 5.7%, p = 0.01). There were no significant differences between the two groups in prostate cancer-specific survival (p = 0.06) or overall survival (p = 0.64). Regarding QOL, there was no significant difference between the two groups in score changes before treatment in the urinary, bowel, sexual, or hormonal domain at 24, 36, 48, 60, or 120 months after LDR-BT.

Conclusion: Celecoxib combined with LDR-BT for prostate cancer was associated with lower cumulative incidence of BCR and metastasis, although QOL impairment was not ameliorated.

Clinical trial registration: UMIN000003649.

Background: Methyl Methanesulfonate-Sensitivity Protein 22-Like (MMS22L) plays a key role in homology-directed DNA repair, and experimental models have shown that its loss confers sensitivity to Poly (ADP-ribose) polymerase inhibitors (PARPi). A rare germline loss-of-function founder mutation in MMS22L, F722fs (c.2164_2168del), was recently identified as a prostate cancer risk factor among individuals of Ashkenazi Jewish ancestry. The impact of this mutation on the disease course following prostate cancer diagnosis remains unclear. Here, we report the longitudinal outcomes of seven MMS22L F722fs carriers diagnosed with different stages of prostate cancer identified at the Brady Urological Institute at Johns Hopkins University.

Methods: We investigated the longitudinal outcomes of seven MMS22L F722fs carriers diagnosed with different stages of prostate cancer identified at the Brady Urological Institute.

Results: With a follow-up time ranging from 5 to 27 years, five of the seven patients who were initially treated with radical prostatectomy remain alive and disease-free, including two patients who had adjuvant and salvage therapies, and one patient who was cured after developing metastatic disease post-surgery. For the remaining two patients with metastatic prostate cancer at diagnosis, one patient responded to ADT for 11 years, and the other died of unknown causes 5 years after diagnosis. None of these patients received PARPi.

Conclusions: Although limited by its retrospective design and small cohort size, this series suggests the potential for exceptional outcomes in F722fs mutation carriers diagnosed with prostate cancer, despite the aggressive disease features and lack of treatment with PARPi. The findings also suggest that prostate cancer patients with this mutation may respond well to standard systemic treatments.

Introduction: It is unknown whether marital status affects years of life lost (YLL) in metastatic prostate cancer (mPCa) according to race/ethnicity.

Methods: Within the SEER database (2004-2021), unmarried and married mPCa patients aged 40-80 years were identified. Age- and sex-matched controls were generated (Social Security Administration life tables and Monte Carlo simulation). YLL were quantified for unmarried and married mPCa patients and controls according to race/ethnicity. Subsequently, multivariable competing risks regression (CRR) models were fitted to assess cancer-specific mortality (CSM) and other-cause mortality (OCM).

Results: Among 34,202 mPCa patients, the distribution of unmarried patients according to race/ethnicity was as follows: 7267 (34.0%) in Caucasians; 3680 (57.0%) in African Americans; 1659 (37.0%) in Hispanics; and 478 (24.0%) in Asians/Pacific Islanders. YLL values in unmarried vs. married patients relative to age- and sex-matched population simulated controls, were as follows: 7.7 vs. 5.8 in Caucasians (Δ: 1.9), 9.6 vs. 7.9 in African Americans (Δ: 1.7), 7.9 vs. 6.7 in Hispanics (Δ: 1.2), and 6.3 vs. 4.7 in Asians/Pacific Islanders (Δ: 1.6). In multivariable CRR models, unmarried status independently predicted higher CSM (1.2-fold, p < 0.001) and OCM (1.2-fold, p < 0.001) in Caucasians, only higher CSM in African Americans (1.1-fold, p = 0.008) and in Asians/Pacific Islanders (1.2-fold, p = 0.02), but only higher OCM in Hispanics (1.5-fold, p < 0.001).

Conclusion: Unmarried mPCa patients exhibited higher YLL values than their married counterparts, relative to age- and sex-matched population simulated controls, across all races/ethnicities. Interestingly, the YLL detriments originated from both CSM and OCM in Caucasians, only CSM in African Americans and Asians/Pacific Islanders, and only OCM in Hispanics.

Background: Genomic prostate score (GPS) may aid clinical decision-making for active surveillance. We assessed whether GPS adds predictive value beyond established clinical variables for adverse pathology at radical prostatectomy (RP) in active surveillance-eligible patients.

Methods: We retrospectively analyzed 387 men with National Comprehensive Cancer Network very-low- to favorable intermediate-risk prostate cancer who underwent Oncotype DX testing followed by RP without active surveillance. Multivariable logistic regression models were constructed to develop prediction models for adverse pathology at RP (Grade Group ≥ 3 and/or ≥ pT3a), including clinical variables (age, PSA, PSA density, biopsy Grade Group 2 [vs. 1], and PI-RADS 4/5) with and without GPS. Model performance was assessed using the AUC with 10-fold cross-validation and compared using DeLong's test, continuous net reclassification improvement (NRI), and decision curve analysis. The incremental predictive value of GPS was also separately evaluated in very low/low-risk and favorable intermediate-risk subgroups.

Results: GPS independently predicted adverse pathology (p < 0.001). The addition of GPS increased the AUC from 0.69 to 0.73 (ΔAUC = 0.036; 95% CI: 0.006-0.065; p = 0.018) and improved reclassification (NRI 0.41, 95% CI: 0.20-0.61). Decision curve analysis demonstrated added net benefit at intermediate threshold probabilities (0.40-0.70), with limited benefit at low thresholds (0.0-0.40). Improvement was significant in the favorable intermediate-risk subgroup (ΔAUC = 0.039; 95% CI: 0.011-0.124; p = 0.026) but not in the very low/low-risk subgroup (ΔAUC = 0.018; 95% CI: -0.043-0.049; p = 0.20). Surgical selection bias was the main limitation.

Conclusions: In this RP cohort, GPS modestly improved prediction of adverse pathology beyond PSA density and MRI, with clinical utility primarily in favorable intermediate-risk patients, where treatment decisions between active surveillance and definitive therapy are uncertain. These findings suggest selective, risk-adapted application of GPS to guide treatment decision-making. Validation in prospective, diverse cohorts is warranted.