Prostate最新文献

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.

Background: As no randomized study has compared abiraterone acetate (ABI) doublet and triplet therapy, the optimal target for the add-on of docetaxel (DTX) to ABI doublet therapy remains unclear. The present study explored patients who may benefit from add-on DTX using initial prostate-specific antigen (PSA) reduction after ABI doublet therapy.

Methods: We retrospectively reviewed 233 patients with CHAATED high-volume metastatic castration-sensitive prostate cancer (mCSPC) treated with ABI doublet therapy. Using the initial PSA half-life calculated by PSA reduction within 6 weeks of treatment (initial PSA^T1/2), a subgroup of patients with a poor overall survival (OS) was explored. The optimal cutoff value of PSA^T1/2 predicting a PSA decline < 90% after 12 weeks of ABI treatment was investigated using a receiver operating characteristic (ROC) analysis.

Results: A PSA^T1/2 of 0.33 months was an ideal cutoff value for predicting a PSA decline < 90% after 12 weeks of ABI treatment. In addition to Grade Group 5 (hazard ratio [HR]: 3.06, p = 0.002) and an LDH ≥ 250 U/L (HR: 2.30, p = 0.017), an initial PSA^T1/2 ≥ 0.33 months (HR: 3.39, p < 0.001) were identified as significant predictors of a poor OS in mCSPC treated with ABI doublet therapy. Only liver metastasis was significantly associated with an initial PSA^T1/2 of ≥ 0.33 months.

Conclusion: We showed that the initial PSA^T1/2 of treatment was significantly prognostic in high-volume mCSPC patients treated with ABI doublet therapy. Our findings suggest that initial PSA reduction may help identify patients who will benefit from the addition of DTX. A prospective study is required to verify our hypotheses.

Introduction: In real-world practice in Japan, standard treatment for metastatic hormone-naïve prostate cancer (mHNPC) is androgen deprivation therapy (ADT), administered as monotherapy, combined androgen blockade (CAB), ADT plus androgen receptor pathway inhibitors (ARPIs), or ADT plus docetaxel. In a previous interim analysis of the large-scale, longitudinal, multicentre, J-ROCK registry study of real-world clinical and patient-reported outcomes, ADT plus ARPI or ADT plus docetaxel was used more frequently than ADT/CAB in patients (aged ≥ 20 years) with newly diagnosed LATITUDE-criteria high-risk mHNPC.

Methods: This post hoc analysis of the J-ROCK study evaluated prostate-specific antigen (PSA) response, progression-free survival (PFS), time to castration-resistant prostate cancer (CRPC), overall survival (OS) and safety in patients with high-risk mHNPC who received ADT/CAB (cohort 1) or ADT plus ARPI (cohort 2B) in subgroups were defined according to the following known prognostic factors at baseline: age, Gleason Grade Group (GGG), alkaline phosphatase (ALP), hemoglobin (Hb) and lactate dehydrogenase (LDH).

Results: This analysis included 947 evaluable patients (371 in cohort 1 and 576 in cohort 2B). PSA response rates remained similar among age and GGG subgroups in both cohorts, but were reduced in cohort 2B patients with elevated ALP, low Hb, and elevated LDH. Time to CRPC and OS were longer in cohort 2B than in cohort 1, regardless of prognostic factors. Among patients with poor prognosis (older, high GGG, low Hb, elevated LDH), OS decline occurred earlier in cohort 1 versus cohort 2B. A trend towards a plateau in the time to CRPC curve was observed in both cohorts, even in patients with poor prognosis. Safety data were not affected by prognostic factors or treatment.

Conclusions: These findings suggest that novel ADT plus ARPI regimens for LATITUDE-criteria high-risk mHNPC may improve real-world outcomes compared with ADT monotherapy or CAB, particularly among patients with poor prognosis.

Background: To question the necessity of simultaneous benign prostatic obstruction (BPO) intervention with cystolitholapaxy in patients with bladder stone (BS) due to BPO and to investigate the factors predicting secondary intervention.

Methods: A total of 235 male patients over 40 years of age who underwent cystolitholapaxy, had a follow-up period longer than 12 months, and were thought to have BS secondary to BPO were included in the study.

Results: A total of 190 patients who did not require additional intervention were defined as Group 1, and 45 patients who required secondary intervention were defined as Group 2. Secondary surgical intervention was required at a rate of 19.5% with an average follow-up of 49 months. Mean peak urine flow rate (Q_max) was 11 m/s in Group 1 and 8.6 m/s in Group 2 (p < 0.001), postvoid residual urine volume (PVR) was 85.5 mL in Group 1 and 115.3 mL in Group 2 (p < 0.001), International Prostate Symptoms Score (IPSS) was 16.7 in Group 1 and 21.7 in Group 2 (p < 0.001). Total prostate volume (TPV) (p = 0.015) and serum prostate-specific antigen (PSA) (p = 0.005) were also significantly higher in Group 2. In the multivariable Cox proportional hazards regression analysis of factors predicting secondary intervention in patients undergoing cystolitholapaxy, low Q_max (hazard ratio (HR) = 0.905, 95% confidence interval (CI): 0.821-0.997, p = 0.043), high PVR (HR = 1.014, 95% CI: 1.007-1.022, p < 0.001), high IPSS (HR = 1.178, 95% CI: 1.106-1.255, p < 0.001) and high PSA (HR = 1.086, 95% CI: 1.000-1.178, p = 0.05) were found to be predictors.

Conclusions: In patients with BS secondary to BPO, performing cystolitholapaxy offers a high likelihood of avoiding secondary intervention. Low Q_max, high PVR, high IPSS, and high PSA are indicators of a higher risk of secondary intervention in the preoperative period. Therefore, in a patient-centered approach, these predictors should be taken into account when deciding whether BPO surgery is necessary in addition to cystolitholapaxy.

Background: Amyloid bodies (corpora amylacea) are found in the prostate and other organs, and their abnormal accumulation can lead to amyloidosis. However, it remains unclear how the constituents and pathological significance of amyloid bodies differ between tissues.

Methods: We performed pathological, proteomic, and biochemical analyzes of prostatic amyloid bodies isolated from 53 consecutive patients who underwent pathological autopsy at Kumamoto University from 2006 to 2017. Amyloid bodies were isolated using laser microdissection, and their constituents were analyzed by liquid chromatography-tandem mass spectrometry, immunohistochemistry, and immunoblotting.

Results: Prostatic amyloid bodies were found in samples from 47 of the 53 patients (89%). The most frequently detected proteins were lactoferrin (100%), S100-A9 (90.9%), prostate-specific antigen (90.9%), and cytoskeleton-associated protein 2-like (90.9%). Amyloid-associated proteins, such as apolipoprotein E (72.7%), vitronectin (54.5%), and serum amyloid P component (36.4%), were also present but were less prevalent. Prostatic amyloid bodies were more common in patients with benign prostatic hyperplasia (N = 25) than in other patients (N = 28).

Conclusions: These results suggest that amyloid bodies from different tissues may share some constituents. Our findings support further investigation to determine the relationship between the constituents of prostatic amyloid bodies and the pathophysiology of prostatic diseases.