Objective:To explore the efficient prognostic factors of cryotherapy for prostate cancer in the real-world setting.Methods:The clinical data of 105 prostate cancer patients treated at the Fudan University Shanghai Cancer center from January 2021 to December 2023 were analyzed retrospectively. The patients were divided into a non-metastatic group (62 cases, 58.7%) and a metastatic group (43 cases, 41.3%) based on the presence or absence of distant metastasis. In the non-metastatic group, the median age was 79 years (range 73 to 82), the initial PSA was 20 ng/ml (range 10 to 47), 37 cases (59.7%) received neoadjuvant endocrine therapy, and the preoperative PSA was 8 ng/ml (range 2 to 14). The ISUP grades were Grade 1 in 4 cases (6.5%), Grade 2 in 11 cases (17.7%), Grade 3 in 16 cases (25.8%), Grade 4 in 16 cases (25.8%), and Grade 5 in 15 cases (24.2%). The T-stages were T 2 in 49 cases, T 3 in 6 cases, and T 4 in 7 cases. All cases were N 0. In the metastatic group, the median age was 68 years (range 62 to 74), the initial PSA was 64 ng/ml (range 27 to 200), 42 cases (97.7%) received neoadjuvant endocrine therapy, and the preoperative PSA was 0 ng/ml (range 0 to 3). The ISUP grades were Grade 1 in 0 cases, Grade 2 in 5 cases (11.6%), Grade 3 in 3 cases (7.0%), Grade 4 in 19 cases (44.2%), and Grade 5 in 16 cases (37.2%). The T-stages were T 2 in 29 cases (67.4%), T 3 in 8 cases (18.6%), and T 4 in 6 cases (14.0%). The N-stages were N 0 in 38 cases (88.4%) and N 1 in 5 cases (11.6%). The M-stages were M 1a in 5 cases (11.6%), M 1b in 35 cases (81.4%), and M 1c in 3 cases (7.0%). The difference in T-stage between the two groups was not statistically significant ( P=0.346), while differences in other indicators were statistically significant ( P<0.05). The cryotherapy for prostate cancer was performed under general or local anesthesia, with the patients in the lithotomy position and a F20 three-lumen catheter was placed for continuous irrigation. Under transrectal ultrasound guidance, the cryoprobes were inserted parallel to the probe through the perineum, with a safe distance of 3 mm from the bladder wall. A whole-gland freezing mode was adopted, starting from the ventral side and freezing layer by layer towards the rectal side. Ultrasound was used in real-time to observe the ice ball's position and extent, adjusting it during ablation to conform to the prostate's margins while protecting surrounding structures. After ablation, the cryoprobes were removed, the puncture sites were disinfected with povidone-iodine, and gauze was applied for 20 seconds to achieve hemostasis before applying dressings. The catheter was removed 10 days postoperatively. PSA levels were rechecked on the first postoperative day and at 6 and 12 weeks postoperatively. The ratio of PSA on the first postoperative day to preoperative PSA was defined as the PSA release rate. Biochemical recurrence was defined as a PSA increase of more than 0.2 ng/ml above the postoperative nadir. The PSA progression-free survival time and the incidence of complications were compared between the two groups. Results:All procedures were successfully completed. The PSA release rates for the non-metastatic and metastatic groups were 4.2 (2.2, 6.4) and 3.9 (1.5, 6.7), respectively, with no statistical significant difference ( P=0.8272). The median PSA at 6 weeks postoperatively was 0.23 (0.01, 1.22) ng/ml, and at 12 weeks it was 0.02 (0.01, 0.49) ng/ml. The median PSA for the non-metastatic group was 0.42 (0.25, 1.00) ng/ml at 6 weeks, and it was 0.03 (0.01, 0.57) ng/ml at 12 weeks. For the metastatic group, the median PSA was 0.30 (0.14, 0.50) ng/ml at 6 weeks, and it was 0.02 (0.01, 1.17) ng/ml at 12 weeks. The median follow-up period was 339 days (range 128 to 571). No Clavien-Dindo grade ≥2 complications occurred postoperatively. One case (0.9%) experienced bladder neck stricture one month postoperatively, which improved by transurethral resection of the prostate (TURP). Two cases (1.9%) experienced urinary retention seven days postoperatively, which resolved after re-catheterization for two weeks. No urinary incontinence was reported. Two non-tumor-related deaths occurred (1.9%), one due to cardiac disease and the other due to complications from COVID-19. During follow-up, 29 cases (27.6%) experienced PSA progression, with a median PSA progression-free survival time of 808.0 days. The median PSA progression-free survival time was not reached in the non-metastatic group, while it was 764.0 days in the metastatic group. There was no statistical significant difference in PSA progression-free survival between the two groups ( P=0.422). Univariate analysis showed that preoperative PSA ( HR=1.02, 95% CI 1.00-1.03, P=0.048), T 3 stage ( HR=9.00, 95% CI 2.59-31.25, P<0.01), and T 4 stage ( HR=5.83, 95% CI 1.68-20.21, P=0.005) were prognostic factors for PSA progression-free survival. Multivariate analysis showed that T 3 stage ( HR=9.08, 95% CI 2.47-33.45, P<0.01) and T 4 stage ( HR=4.50, 95% CI 1.18-17.22, P=0.028) were independent prognostic factors for PSA progression-free survival. Conclusions:Cryotherapy for prostate cancer has a high safety profile. The efficacy of Cryotherapy is better in patients with T-stage

Ductal adenocarcinoma(DAC)is the most common histological variant of prostate cancer with an aggressive characteristic.Due to the rarity of the disease,DAC can be difficult to identify by traditional diagnostic modalities such as serum prostate-specific antigen(PSA)and multi-parameter magnetic resonance imaging.Optimal treatment mode for local DAC is still under exploration.After radical prostatectomy or radiotherapy,most DACs are prone to recurrence or metastasis at low PSA levels,and systemic therapy for high-risk prostate cancer is less effective in the treatment of DAC.Current genomic analysis of DAC has provided laboratory evidence for its aggressive behavior and potential therapeutic targets,but the exploration of the mechanism of the biological behavior of DAC still needs to be addressed.

Background and purpose:Both prostate-specific membrane antigen(PSMA)positron emission tomography/computed tomography(PET/CT)and circulating tumor DNA(ctDNA)sequencing outcomes serve as references for therapeutic decision-making in hormone-sensitive prostate cancer(HSPC)treatment.This study aimed to analyze the association between PSMA PET/CT-derived parameters and ctDNA characteristics in patients with HSPC.Methods:HSPC patients who received PSMA PET/CT and ctDNA sequencing at an interval of less than 2 weeks and with complete medical records were retrospectively included in Fudan University Shanghai Cancer Center.Patients with active malignancies other than prostate cancer and those with histological features supporting a diagnosis of pure neuroendocrine carcinoma or small cell carcinoma were excluded.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethics number:1909207-12).The correlation between PSMA PET/CT-derived parameters,including the maximum standardized uptake value(SUVmax),total tumor volume(TTV),total lesion uptake(TLU)and ctDNA fraction(ctDNA%)was evaluated using the Spearman correlation coefficient.Results:A total of 60 HSPC patients were included,with TP53(3.3%),BRCA2(3.3%)and ATM(3.3%)being the most common mutated genes.In the correlation analysis,a significant correlation was observed between ctDNA%and SUVmax levels(Spearman's rho=0.272,P=0.036);however,no significant correlation was found between ctDNA%and TLU(Spearman's rho=0.160,P=0.222)or TTV(Spearman's rho=0.162,P=0.215).Conclusion:There was a significant correlation between SUVmax and ctDNA%,suggesting that patients with high PSMA uptake lesions were more likely to receive combined targeted therapy than patients with no PSMA positive lesions and patients with low PSMA uptake lesions,which provided a certain reference for the formulation of individualized treatment plans.

Background and purpose:Human epidermal growth factor receptor 2(HER2)is closely associated with drug efficacy and prognosis in urothelial carcinoma(UC).HER2 is a significant biomarker and therapeutic target in various tumors.In recent years,anti-HER2 antibody-drug conjugates have shown significant clinical efficacy in UC patients with HER2 overexpression.Therefore,an in-depth understanding of HER2 expression and its characteristics in Chinese UC patients is crucial to guide treatment decision-making,optimize treatment strategies and achieve personalized therapy.This study aimed to thoroughly investigate correlation of HER2 expression and clinicopathological characteristics in Chinese patients with UC.Methods:This study was a multicenter study that retrospectively included UC patients from urology departments of 8 tertiary hospitals in 5 geographical regions of China(North China,East China,South China,Central China and Northwest)whose tissue samples were collected from January 2023 to March 2024.Inclusion criteria:① age above 18 years;② UC diagnosed by histopathological or cytological examination;③ complete results of HER2 expression detection using immunohistochemistry(IHC)in the primary tumor site were required.Exclusion criteria:① diagnosed patients with tumors in other parts of the body;② physicians evaluated other situations that were not suitable for inclusion in this study.IHC results for HER2 expression and clinicopathological data were collected.HER2 expression was determined according to the criteria outlined in"Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China",with HER2 2+and 3+defined as HER2 overexpression.The HER2 expression and clinicopathological features were analyzed.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical number:2301268-12)and was registered at China Clinical Trial Registry(registration number:ChiCTR2300069746).Results:A total of 1054 patients with UC were included.Most of the tumors were bladder UC(n=807,76.6%).The mean age of patients was(66.8±10.5)years,and the majority were male(78.5%).The HER2 overexpression rate was 58.4%(n=616),with an additional 23%of patients having HER2 1+expression(n=242),and a small proportion exhibiting negative HER2 expression(n=196,18.6%).HER2 expression was significantly associated with various clinical and pathological characteristics such as Eastern Cooperative Oncology Group(ECOG)performance status,history of cardiovascular disease,history of metabolic disorders,smoking,UC disease location,differentiation grade,pathological type,and tumor stage.Conclusion:Retrospective analysis of multi-center data shows that HER2 expression is frequently observed in Chinese UC patients,with an overexpression rate of up to 58.4%.Furthermore,HER2 expression is closely associated with various clinical and pathological features of UC patients.This study underscores the critical importance of accurately assessing HER2 expression in UC patient to guide personalized therapies.

Objective:To analyze germline pathogenic mutations in patients with upper tract urothelial carcinoma(age≤60 years old), and to explore the clinicopathological characteristics of germline pathogenic mutation carriers.Methods:The data of 124 patients (age≤60 years old) with upper tract urothelial carcinoma who underwent germline genetic testing at Fudan University Shanghai Cancer Center from September 2008 to February 2023 were retrospectively analyzed. There were 86 males and 38 females, and the median age was 55.0(49.8, 58.0)years old. The primary tumors were located in the renal pelvis in 81 cases (65.3%), the ureter in 34 cases (27.4%), and both in 9 cases (7.3%). There were 13 patients (10.5%) with low-grade UTUC and only 8 patients (6.5%) with carcinoma in situ. Twelve patients (9.7%) had a history of bladder cancer and 12 (9.7%) had a history of malignancy other than bladder cancer. Whole gene exome sequencing or target region sequencing was performed to explore germline mutations associated with patients with UTUC. The germline genetic testing data were interpreted in accordance with the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP)2015 edition guideline to clarify the germline pathogenic mutation rate and elucidate the clinicopathological characteristics of germline pathogenic mutation carriers. Germline pathogenic mutation rates were further compared with those of healthy East Asian populations to analyze germline mutations associated with the risk of carcinogenesis in UTUC.Results:In this study, 31 germline pathogenic mutations were detected in 28 (22.6%) of 124 patients with UTUC. There were no statistically significant differences in age [54.0 (47.0, 58.0) years old vs. 56.0 (50.8, 58.0) years old], gender (male/female: 21/7 vs. 65/31), history of bladder cancer (0 vs. 12/96), T-stage (T 3-4: 12/28 vs. 41/96), and proportion of histologic high-level (26/28 vs. 85/96) between patients with and without germline pathogenic mutations ( P>0.05). The 31 germline pathogenic mutations were located in 22 genes, including BRCA2 (4, 12.9%), MSH2 (3, 9.7%), RAD54L (2, 6.5%), BRCA1 (2, 6.5%), BRIP1 (2, 6.5%), NOTCH3 (2, 6.5%), XRCC2 (1, 3.2%), VEGFA (1, 3.2%), TBX3 (1, 3.2%), RET (1, 3.2%), PRKN (1, 3.2%), PALB2 (1, 3.2%), NTRK1 (1, 3.2%), NCOA3 (1, 3.2%), MSH6 (1, 3.2%), LRP1B (1, 3.2%), KMT2D (1, 3.2%), KMT2A (1, 3.2%), FANCA (1, 3.2%), BARD1 (1, 3.2%), ARID1A (1, 3.2%), and AR (1, 3.2%). The germline pathogenic mutation rates of 124 patients were compared with those of the healthy East Asian population. The results showed that germline pathogenic mutations in BRCA2 ( OR = 11.9, 95% CI 3.8 - 37.7, P<0.001), MSH2 ( OR = 11.9, 95% CI 3.2-44.5, P<0.001), RAD54L ( OR=14.2, 95% CI 2.7-73.8, P=0.002) and BRCA1 ( OR=11.8, 95% CI 2.4-59.1, P=0.003) genes significantly increase the risk of developing UTUC. Conclusions:The rate of germline pathogenic mutations in ≤60 years old UTUC patients in this study was 22.6%, and germline pathogenic mutations carrying germline BRCA2, MSH2, RAD54L or BRCA1 genes significantly increased the risk of developing UTUC.

The 2023 European Society for Medical Oncology (ESMO) was held recently. In this conference, numbers of cutting-edge studies were discussed and published including advances in diagnosis and treatment, especially in prostate cancer. Studies that may influence clinical treatment decisions were summarized in this article, including timing of radiotherapy after radical prostatectomy, Enzalutamide in biochemically recurrent prostate cancer, predictive factors of novel hormonal therapies in metastatic hormone-sensitive prostate cancer, and the value of osteoprotective agent. The purpose of this article was to help clinicians make better clinical decisions.

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*

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To explore clinical value of prostate target biopsy guided by multiparametric magnetic resonance imaging (mpMRI) and 68Ga-labeled prostate specific membrane antigen ligand imaging positron emission tomography/X-ray computed tomography ( 68Ga-PSMA PET/CT) image fusion. Methods:The data of 50 patients admitted to Fudan University Shanghai Cancer Center from January 2021 to February 2022 who underwent mpMRI and 68Ga-PSMA PET/CT to guide prostate biopsy were retrospectively analyzed. The median age was 70 (63-79) years, the median serum tPSA value was 8.1 (6.8-83.0) ng/ml, and the prostate volume was 45.5 (30-80) ml. 36 cases were positive by mpMRI, including PI-RADS score 3 in 5 cases, 4 score in 19 cases, 5 score in 12 cases. 32 cases were positive by 68Ga-PSMA PET/CT examination, of which 30 cases were double positive and the fusion of both imaging techniques was positive, referred to as PET/CT-MRI. The patient's mpMRI and 68Ga-PSMA PET/CT images were imported into the MIM fusion software, and the outline of the prostate and the target area were outlined respectively. When PET/CT and MRI double positive cases were biopsied, the two images were alternately fused, calibrated and locked with the real-time prostate ultrasound interface(PET/CT-MRI). Single-positive cases were guided by positive images to complete targeted biopsy, and 12-needle systematic biopsies were completed after targeted biopsy and double-negative cases. The advantages of targeted biopsy and systematic biopsy was evaluated, and the diagnostic performance (sensitivity, specificity, positive predictive value, and negative predictive value) was analyzed. Results:Among the 50 biopsy patients in this group, 31 (62%) had prostate cancer, of which 22 (44%) were CsPCa. There was no significant difference in the detection rate of prostate cancer between targeted biopsy and systematic biopsy [78.9% (30/38) and 62.0% (31/50), P=0.088], and there was no significant difference in the detection rate of CsPCa [57.9% (22/38) and 40.0% (20/50), P=0.096]. The positive rate of the biopsy needles number was significantly different [86.3% (69/80) and 19.0% (114/ 600), P<0.001]. The detection rates of prostate cancer in mpMRI positive, PET/CT positive and PET/CT-MRI positive cases were 83.3% (30/36), 90.6% (29/32) and 96.6% (29/30) respectively, the detection rates of CsPCa were 61.1% (22/36), 68.8% (22/32) and 73.3% (22/30) respectively.The sensitivity, specificity, positive predictive value and negative predictive value of mpMRI in the diagnosis of prostate cancer were 96.8%(30/31), 68.4%(13/19), 83.3%(30/36)and 92.9%(13/14), respectively.Those values in 68Ga-PSMA PET/CT were 93.5%(29/31), 84.2%(16/19), 90.6%(29/32)and 88.9%(16/18), respectively.Those values in PET/CT-MRI were 93.8%(29/31), 94.7%(18/19), 96.7%(29/30)and 90.0%(18/20), respectively. The above four indicators of mpMRI diagnosis of CsPCa were 100.0%(22/22), 50.0%(14/28), 61.1%(22/36)and 100.0%(14/14), respectively.Those indicators in 68Ga-PSMA PET/CT were 100.0%(22/22), 64.3%(18/28), 68.8%(22/32)and 100.0%(18/18), respectively.Those indicators in PET/CT-MRI was 100.0%(22/22), 71.4%(20/28), 73.2%(22/30)and 100.0%(20/20), respectively. The detection efficiency of PET/CT-MRI was better than that of mpMRI (Kappa value was 0.737, P=0.031). Conclusions:PET/CT-MRI image fusion-guided targeted prostate biopsy can effectively improve the detection efficiency of prostate cancer and clinically significant prostate cancer, and increase the positive rate.

Objective:To analyze germline genetic testing in Chinese high-to very-high-risk non-metastatic prostate cancer patients.Methods:This study included 249 Chinese patients with high- to very-high-risk non-metastatic prostate cancer for germline genetic testing, in Fudan University Shanghai Cancer Center, West China Hospital and Cancer Center of Sun Yat-sen University, from January 2018 to December 2022. High risk and very-high risk are termed according to National Comprehensive Cancer Network (NCCN) Prostate Cancer Guideline (2022 V1). The mean age of the patients was (66.7±9.2) years old and median PSA level was 28.50 (ranging 2.43 - 1481.11) ng/ml. Within these 249 patients, 84 (33.7%) were T 1-2, 98 (39.3%) were T 3-4, while 67 (26.9%) were unclear in T stage. Additionally, 51 patients (20.5%) were classified into International Society of Urological Pathology(ISUP) grade group 1-3 group and 198 patients (79.5%) were in ISUP 4-5 group. Focusing on 16 genetic susceptibility genes for prostate cancer, we interpret the germline genetic testing data in accordance with the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guideline, clarify the germline pathogenic mutation rate and elucidate the clinicopathological characteristics of germline pathogenic mutation carriers. Results:Among Chinese high-to very-high-risk non-metastatic prostate cancer patients, 7.2% (18/249) had germline pathogenic mutations. Patients with mutations had a significantly higher proportion of first-degree relatives with a history of malignancy than those without mutations (50% vs. 13%, P<0.001), but there was no difference in age of onset [(68.2±9.3)years vs. (66.6±9.2) years], PSA level (median: 40.68 ng/ml vs. 28.00 ng/ml), T stage [T 3-4: 38.9%(7/18)vs. 39.4%(91/231)] and ISUP grade [group 4-5: 88.9%(16/18) vs. 78.8%(182/231)]. Germline pathogenic mutations were observed in BRCA2 (7 patients, 38.9%), MSH2 (3 patients, 16.7%), PALB2 (2 patients, 11.1%), ATM (2 patients, 11.1%), RAD51C (1 patient, 5.6%), PMS2 (1 patient, 5.6%), MSH6 (1 patient, 5.6%) and HOXB13 (1 patient, 5.6%). By comparing with normal controls of East-Asian population, germline pathogenic mutations in BRCA2 ( OR=11.1, 95% CI 4.8-25.6, P<0.001) and MSH2 ( OR= 43.5, 95% CI 8.5-200.0, P<0.001) can significantly increase the risk of developing high- to very-high-risk prostate cancer in Chinese males. Conclusions:This study identified a germline pathogenic mutation rate of 7.2% in 249 Chinese patients with high- or very-high-risk non-metastatic prostate cancer. Carrying germline BRCA2 or MSH2 pathogenic mutations can significantly increase the risk of high- or very-high-risk prostate cancer in Chinese men.