Objective To investigate the clinicopathological features,immunohistochemical features,diagnosis,and relationship with sporadic prostate cancer in primary small cell neuroendocrine carcinoma of the bladder. Methods We retrospectively analyzed the clinical characteristics of 12 patients with primary small cell neuroendocrine carcinoma of the bladder diagnosed at Beijing Chao-Yang Hospital affiliated to Capital Medical University from January 2013 to September 2022.The histological features of primary small cell neuroendocrine carcinoma of the bladder were re-evaluated by two pathologists according to the 2022 revision of the World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs.Electronic medical records were retrieved,and telephone follow-up was conducted from the time of histopathological diagnosis to the death or the end of the last follow-up until January 31,2023. Results The 12 patients include 7 patients in pT3 stage and 1 patient in pT4 stage.Eight patients were complicated with other types of tumors,such as high-grade urothelial carcinoma of the bladder and squamous cell carcinoma.Five patients had sporadic prostate cancer.Immunohistochemical staining showed that 12 (100.0%),10 (83.3%),and 8 (66.7%) patients were tested positive for CD56,Syn,and CgA,respectively.The Ki67 proliferation index ranged from 80% to 90%.Five patients with urothelial carcinoma were tested positive for CK20,GATA3,and CK7.P504S was positive in all the 5 patients with prostate cancer,while P63 and 34βE12 were negative.The follow-up of the 12 patients lasted for 3-60 months.Eight of these patients died during follow-up,with the median survival of 15.5 months.Four patients survived. Conclusions Primary small cell neuroendocrine carcinoma of the bladder is a rare urological tumor with high aggressiveness and poor prognosis.In male patients with bladder prostatectomy,all prostate tissue should be sampled.If prostate cancer is detected,the prostate-specific antigen level should be monitored.
Humans ; Male ; Carcinoma, Transitional Cell/pathology* ; Carcinoma, Neuroendocrine/pathology* ; Urinary Bladder Neoplasms/pathology* ; Urinary Bladder/pathology* ; Retrospective Studies ; Prostatic Neoplasms ; Biomarkers, Tumor

The long-term survival outcomes of radical prostatectomy (RP) in Chinese prostate cancer (PCa) patients are poorly understood. We conducted a single-center, retrospective analysis of patients undergoing RP to study the prognostic value of pathological and surgical information. From April 1998 to February 2022, 782 patients undergoing RP at Queen Mary Hospital of The University of Hong Kong (Hong Kong, China) were included in our study. Multivariable Cox regression analysis and Kaplan-Meier analysis with stratification were performed. The 5-year, 10-year, and 15-year overall survival (OS) rates were 96.6%, 86.8%, and 70.6%, respectively, while the 5-year, 10-year, and 15-year PCa-specific survival (PSS) rates were 99.7%, 98.6%, and 97.8%, respectively. Surgical International Society of Urological Pathology PCa grades (ISUP Grade Group) ≥4 was significantly associated with poorer PSS (hazard ratio [HR] = 8.52, 95% confidence interval [CI]: 1.42-51.25, P = 0.02). Pathological T3 stage was not significantly associated with PSS or OS in our cohort. Lymph node invasion and extracapsular extension might be associated with worse PSS (HR = 20.30, 95% CI: 1.22-336.38, P = 0.04; and HR = 7.29, 95% CI: 1.22-43.64, P = 0.03, respectively). Different surgical approaches (open, laparoscopic, or robotic-assisted) had similar outcomes in terms of PSS and OS. In conclusion, we report the longest timespan follow-up of Chinese PCa patients after RP with different approaches.
Male ; Humans ; Retrospective Studies ; Prostatic Neoplasms/pathology* ; Prostate/pathology* ; Prostatectomy ; Prognosis ; Neoplasm Grading

A complete proteomics study characterizing active androgen receptor (AR) complexes in prostate cancer (PCa) cells identified a diversity of protein interactors with tumorigenic annotations, including known RNA splicing factors. Thus, we chose to further investigate the functional role of AR-mediated alternative RNA splicing in PCa disease progression. We selected two AR-interacting RNA splicing factors, Src associated in mitosis of 68 kDa (SAM68) and DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) to examine their associative roles in AR-dependent alternative RNA splicing. To assess the true physiological role of AR in alternative RNA splicing, we assessed splicing profiles of LNCaP PCa cells using exon microarrays and correlated the results to PCa clinical datasets. As a result, we were able to highlight alternative splicing events of clinical significance. Initial use of exon-mini gene cassettes illustrated hormone-dependent AR-mediated exon-inclusion splicing events with SAM68 or exon-exclusion splicing events with DDX5 overexpression. The physiological significance in PCa was investigated through the application of clinical exon array analysis, where we identified exon-gene sets that were able to delineate aggressive disease progression profiles and predict patient disease-free outcomes independently of pathological clinical criteria. Using a clinical dataset with patients categorized as prostate cancer-specific death (PCSD), these exon gene sets further identified a select group of patients with extremely poor disease-free outcomes. Overall, these results strongly suggest a nonclassical role of AR in mediating robust alternative RNA splicing in PCa. Moreover, AR-mediated alternative spicing contributes to aggressive PCa progression, where we identified a new subtype of lethal PCa defined by AR-dependent alternative splicing.
Humans ; Male ; Alternative Splicing ; Cell Line, Tumor ; DEAD-box RNA Helicases/metabolism* ; Disease Progression ; Gene Expression Regulation, Neoplastic ; Prostatic Neoplasms/pathology* ; Receptors, Androgen/metabolism* ; RNA Splicing Factors/metabolism*

The purpose of this study was to explore transrectal ultrasound (TRUS) findings of prostate cancer (PCa) guided by multiparametric magnetic resonance imaging (mpMRI) and to improve the Prostate Imaging Reporting and Data System (PI-RADS) system for avoiding unnecessary mpMRI-guided targeted biopsy (TB). From January 2018 to October 2019, fusion mpMRI and TRUS-guided biopsies were performed in 162 consecutive patients. The study included 188 suspicious lesions on mpMRI in 156 patients, all of whom underwent mpMRI-TRUS fusion imaging-guided TB and 12-core transperineal systematic biopsy (SB). Univariate analyses were performed to investigate the relationship between TRUS features and PCa. Then, logistic regression analysis with generalized estimating equations was performed to determine the independent predictors of PCa and obtain the fitted probability of PCa. The detection rates of PCa based on TB alone, SB alone, and combined SB and TB were 55.9% (105 of 188), 52.6% (82 of 156), and 62.8% (98 of 156), respectively. The significant predictors of PCa on TRUS were hypoechogenicity (odds ratio [OR]: 9.595, P = 0.002), taller-than-wide shape (OR: 3.539, P = 0.022), asymmetric vascular structures (OR: 3.728, P = 0.031), close proximity to capsule (OR: 3.473, P = 0.040), and irregular margins (OR: 3.843, P = 0.041). We propose subgrouping PI-RADS score 3 into categories 3a, 3b, 3c, and 3d based on different numbers of TRUS predictors, as the creation of PI-RADS 3a (no suspicious ultrasound features) could avoid 16.7% of mpMRI-guided TBs. Risk stratification of PCa with mpMRI-TRUS fusion imaging-directed ultrasound features could avoid unnecessary mpMRI-TBs.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Multiparametric Magnetic Resonance Imaging ; Magnetic Resonance Imaging/methods* ; Prostate/pathology* ; Image-Guided Biopsy/methods*

OBJECTIVES: To investigate the prevalence of pathogenic germline mutations of mismatch repair (MMR) genes in prostate cancer patients and its relationship with clinicopathological characteristics. METHODS: Germline sequencing data of 855 prostate cancer patients admitted in Fudan University Shanghai Cancer Center from 2018 to 2022 were retrospectively analyzed. The pathogenicity of mutations was assessed according to the American College of Medical Genetics and Genomics (ACMG) standard guideline, Clinvar and Intervar databases. The clinicopathological characteristics and responses to castration treatment were compared among patients with MMR gene mutation (MMR⁺ group), patients with DNA damage repair (DDR) gene germline pathogenic mutation without MMR gene (DDR⁺MMR^－ group) and patients without DDR gene germline pathogenic mutation (DDR^－ group). RESULTS: Thirteen (1.52%) MMR⁺ patients were identified in 855 prostate cancer patients, including 1 case with MLH1 gene mutation, 6 cases with MSH2 gene mutation, 4 cases with MSH6 gene mutation and 2 cases with PMS2 gene mutation. 105 (11.9%) patients were identified as DDR gene positive (except MMR gene), and 737 (86.2%) patients were DDR gene negative. Compared with DDR^－ group, MMR⁺ group had lower age of onset (P<0.05) and initial prostate-specific antigen (PSA) (P<0.01), while no significant differences were found between the two groups in Gleason score and TMN staging (both P>0.05). The median time to castration resistance was 8 months (95%CI: 6 months-not achieved), 16 months (95%CI: 12-32 months) and 24 months (95%CI: 21-27 months) for MMR⁺ group, DDR⁺MMR^－ group and DDR^－ group, respectively. The time to castration resistance in MMR⁺ group was significantly shorter than that in DDR⁺MMR^－ group and DDR^－ group (both P<0.01), while there was no significant difference between DDR⁺MMR^－ group and DDR^－ group (P>0.05). CONCLUSIONS MMR gene mutation testing is recommended for prostate cancer patients with early onset, low initial PSA, metastasis or early resistance to castration therapy.
Male ; Humans ; Prostate-Specific Antigen/genetics* ; Germ-Line Mutation ; Retrospective Studies ; DNA Mismatch Repair/genetics* ; DNA-Binding Proteins/metabolism* ; China ; Prostatic Neoplasms/pathology*

The American Urological Association (AUA), European Association of Urology (EUA) and International Urological Society (SIU) annual meetings were held in 2022. Studies on prostate cancer reported in the meetings mainly focus on the advances of diagnostic biomarkers (such as α-2, 3-1inked sialylation of terminal N-glycan on free PSA density, SelectMDx) and imaging techniques [such as multiparametric magnetic resonance imaging, prostate specific membrane antigen(PSMA)-PET/CT], the new method for prostate biopsy, the new treatments of prostate cancer including [¹⁷⁷Lu] Ludotadipep and DROP-IN PSMA probe, and the prognosis assessment of prostate cancer (such as AR-V7). This article provides an overview on the research hotspots of three international academic meetings.
Male ; Humans ; Urology ; Positron Emission Tomography Computed Tomography/methods* ; Prostatic Neoplasms/pathology* ; Multiparametric Magnetic Resonance Imaging/methods* ; Gallium Radioisotopes

Objective: To analyze three different integrated scoring schemes of prostate biopsy and to compare their concordance with the scoring of radical prostatectomy specimens. Methods: A retrospective analysis of 556 patients with radical prostatectomy performed in Nanjing Drum Tower Hospital, Nanjing, China from 2017 to 2020. In these cases, whole organ sections were performed, the pathological data based on biopsy and radical prostatectomy specimens were summarized, and 3 integrated scores of prostate biopsy were calculated, namely the global score, the highest score and score of the largest volume. Results: Among the 556 patients, 104 cases (18.7%) were classified as WHO/ISUP grade group 1, 227 cases (40.8%) as grade group 2 (3+4=7); 143 cases (25.7%) as grade group 3 (4+3=7); 44 cases (7.9%) as grade group 4 (4+4=8) and 38 cases (6.8%) as grade group 5. Among the three comprehensive scoring methods for prostate cancer biopsy, the consistency of global score was the highest (62.4%). In the correlation analysis, the correlation between the scores of radical specimens and the global scores was highest (R=0.730, P<0.01), while the correlations of the scores based on radical specimens with highest scores and scores of the largest volume based on biopsy were insignificant (R=0.719, P<0.01; R=0.631, P<0.01, respectively). Univariate and multivariate analyses showed tPSA group and the three integrated scores of prostate biopsy were statistically correlated with extraglandular invasion, lymph node metastasis, perineural invasion and biochemical recurrence. Elevated global score was an independent prognostic risk factor for extraglandular invasion and biochemical recurrence in patients; increased serum tPSA was an independent prognostic risk factor for extraglandular invasion; increased hjighest score was an independent risk factor for perineural invasion. Conclusions: In this study, among the three different integrated scores, the overall score is most likely corresponded to the radical specimen grade group, but there is difference in various subgroup analyses. Integrated score of prostate biopsy can reflect grade group of radical prostatectomy specimens, thereby providing more clinical information for assisting in optimal patient management and consultation.
Male ; Humans ; Prostate/pathology* ; Retrospective Studies ; Prostatectomy/methods* ; Biopsy ; Prostatic Neoplasms/pathology*

Magnetic resonance imaging (MRI)-targeted prostate biopsy is the recommended investigation in men with suspicious lesion(s) on MRI. The role of concurrent systematic in addition to targeted biopsies is currently unclear. Using our prospectively maintained database, we identified men with at least one Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesion who underwent targeted and/or systematic biopsies from May 2016 to May 2020. Clinically significant prostate cancer (csPCa) was defined as any Gleason grade group ≥2 cancer. Of 545 patients who underwent MRI fusion-targeted biopsy, 222 (40.7%) were biopsy naïve, 247 (45.3%) had previous prostate biopsy(s), and 76 (13.9%) had known prostate cancer undergoing active surveillance. Prostate cancer was more commonly found in biopsy-naïve men (63.5%) and those on active surveillance (68.4%) compared to those who had previous biopsies (35.2%; both P < 0.001). Systematic biopsies provided an incremental 10.4% detection of csPCa among biopsy-naïve patients, versus an incremental 2.4% among those who had prior negative biopsies. Multivariable regression found age (odds ratio [OR] = 1.03, P = 0.03), prostate-specific antigen (PSA) density ≥0.15 ng ml^-2 (OR = 3.24, P < 0.001), prostate health index (PHI) ≥35 (OR = 2.43, P = 0.006), higher PI-RADS score (vs PI-RADS 3; OR = 4.59 for PI-RADS 4, and OR = 9.91 for PI-RADS 5; both P < 0.001) and target lesion volume-to-prostate volume ratio ≥0.10 (OR = 5.26, P = 0.013) were significantly associated with csPCa detection on targeted biopsy. In conclusion, for men undergoing MRI fusion-targeted prostate biopsies, systematic biopsies should not be omitted given its incremental value to targeted biopsies alone. The factors such as PSA density ≥0.15 ng ml^-2, PHI ≥35, higher PI-RADS score, and target lesion volume-to-prostate volume ratio ≥0.10 can help identify men at higher risk of csPCa.
Male ; Humans ; Prostate/pathology* ; Prostatic Neoplasms/pathology* ; Prostate-Specific Antigen ; Magnetic Resonance Imaging/methods* ; Image-Guided Biopsy/methods* ; Retrospective Studies

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.
Male ; Humans ; Prostate/pathology* ; Prostate-Specific Antigen/analysis* ; Prostatic Neoplasms/diagnostic imaging* ; Biopsy ; Nomograms ; Retrospective Studies

Male ; Humans ; Prostatic Neoplasms/pathology* ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Hormones ; Androgen Antagonists/therapeutic use*