Prostate Cancer In Chinese Men Research Articles

Abstract 1433: FOXA1 alterations distinctively drive prostate tumorigenesis or therapy resistance in mice

Abstract Androgen receptor (AR) signaling is critical for survival of prostate cancer (PCa) cells, thus making androgen deprivation therapy (ADT; e.g., castration) as the mainstay for treatment. Notably, oncogenic functions of AR rely on chromatin-binding regulatory proteins, which includes a pioneer transcription factor called FOXA1. FOXA1 de-compacts chromatin to enable AR’s binding to the DNA and expression of it's target genes. Recently, our lab found FOXA1 alterations to recur within three distinct structural classes in over 35% of metastatic castration resistant PCa (mCRPC) in Caucasian men. Subsequent studies found FOXA1 mutations to be prevalent in over 40% of primary PCa in Chinese men, positioning FOXA1 as a principal oncogene in this disease. Yet, hitherto, no studies have defined the pathobiology of FOXA1 alterations in mouse models. Here, we have developed the first-in-field transgenic mice with conditional overexpression of FOXA1 mutants in the prostate luminal epithelia. We found truncal FOXA1 Class1 mutants to initiate luminal hyperplasia in a monogenic model, or hyperproliferative prostate adenocarcinoma in a compound Trp53-deficient genetic background. Mechanistically, Class1 mutants concurrently upregulate the AR and mTORC1/2 pathways to drive transformation, with this being the first report of FOXA1-driven PCa formation in mice. In contrast, FOXA1 Class2 mutants—which are acquired in mCRPC—do not drive prostate luminal transformation. Instead, single-cell multi-omics (RNA+ATAC) profiling of Class2-mutant mouse prostate tissue uncovered extensive transcriptional remodeling of epithelial cells into a luminal stem-like cell fate, leading to a dramatic 15-20-fold expansion of the progenitor population vs control tissue. These luminal stem cells are similar to the Club/Hillock cells detected in the human prostate that have been implicated in driving resistance to ADT. Consistently, we found Class2-mutant prostates to show minimal atrophy upon castration, with immunohistological assessment uncovering a higher density of Ki67+ luminal epithelial cells relative to wild type and Class1 tissues. Class2-mutant organoids also showed higher subcutaneous grafting ability in mice in limiting dilution assays. Mechanistically, we found the cistromically-dominant Class2 mutants to pioneer over 40,000 neo-enhancer elements harboring motifs of stemness-associated transcription factors, which in turn instruct the ADT-resistant luminal progenitor gene program. Altogether, findings from our mouse models uncover FOXA1’s versatility as a driver oncogene that, depending on the mutation type, either activates enhancer-wired luminal tumorigenesis (Class1-initiating event) or therapy resistance-associated stemness (Class2-promoting alteration) gene programs in the mouse prostate tissue. Citation Format: Sanjana Eyunni, Abhijit Parolia, Eleanor Young, James Matthew George, Rahul Mannan, Sandra E. Carson, Yuping Zhang, Jean Tien, Mustapha Jaber, Jie Luo, Matthew Pang, Rohit Mehra, Xuhong Cao, Fengyun Su, Rui Wang, Marcin Cieslik, Dong Kee Lee, Jianming Xu, Arul M. Chinnaiyan. FOXA1 alterations distinctively drive prostate tumorigenesis or therapy resistance in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1433.

The Association Between Metabolic Syndrome and Prostate Cancer Risk: A Large-Scale Investigation and Study of Chinese.

BackgroundTo investigate the association between metabolic syndrome (MetS) and its components and prostate cancer (PCa).MethodsThis study enrolled 482 943 consecutive men who underwent routine health checkups at the Health Management Center of West China Hospital Between 2010 and 2017. For patients with elevated prostate-specific antigen (PSA) levels or color Doppler ultrasound indicating abnormal prostates, we recommended prostate puncture and follow-up. We used the chi-square test and independent t-test for categorical variables and continuous variables, respectively. We used logistic regression analysis to evaluate the effects of MetS and its components on prostate cancer risk.ResultsWe found that the incidence of PCa in Chinese men over 40 years of age was 0.1%. Among the 85882 participants, 31.5% (27016/85882) of the patients were diagnosed with MetS. PCa was associated with older age, higher PSA levels, lighter weight and shorter height, hypertension, elevated fasting blood glucose (FBG) and HDL cholesterol level, lower triglycerides. After excluded the interference of other factors in multivariate logistic analysis, we found that MetS, hypertension, hyperlipidemia, hyperglycemia, and obesity were not related to the risk of PCa. High age and PSA levels were risk factors for prostate cancer.ConclusionsHigh age and PSA levels were risk factors for prostate cancer. MetS, hypertension, hyperlipidemia, hyperglycemia, and obesity were not related to the risk of PCa.

Morbidity and All-Cause Mortality Following Radical Prostatectomy Compared with Observation for Localized Prostate Cancer in Chinese Men: A Non-Randomized Retrospective Study.

BackgroundThe Chinese 2018 guidelines and the current 2014 Chinese Urological Association guidelines for prostate cancer recommend radical prostatectomy for Chinese men with localized prostate cancer as the first choice, but it has treatment-related adverse effects. This study aimed to study morbidity and all-cause mortality following radical prostatectomy compared with observation for localized prostate cancer in Chinese men from a single center.Material/MethodsMen diagnosed (histologically) as stage T1-T2N×M0 prostate cancer of any grade with 1-year history were included in the analysis. A total of 201 men underwent radical prostatectomy (RP cohort) and 209 men did not undergo radical prostatectomy (OS cohort).ResultsDuring follow-up (17–24 years), 135 (67%) men died in the RP cohort and 156 (75%) men died in the OS cohort (P=0.103). All-cause mortality was lower for men with prostate-specific antigen level >10 ng/mL (P<0.0001), Gleason score ≥7 (P=0.004), and high D’Amico tumor risk scores (P=0.007) if they underwent radical prostatectomy. Age ≥65 years (P=0.041), Gleason score ≥7 (P=0.049), and tumor stage ≥2c (P=0.045) were associated with all-cause mortality.ConclusionsThe findings from this study showed that radical prostatectomy has no significant beneficial effects when compared with observation for Chinese men with localized prostate cancer, unless they had a prostate-specific antigen level >10 ng/mL, Gleason score ≥7, and high D’Amico tumor risk scores.

Prostate cancer: Race and prostate cancer personalized medicine: the future.

Most genetic analyses of prostate cancer have studied white men. A new study compares the genetic landscape of prostate cancer in Chinese men, reporting both similarities and differences. This finding highlights the need for studies to include all races and paves the way for future personalized medicine approaches for prostate cancer across races.

Use of prostate health index in diagnosing prostate cancer in Chinese men

Objective: To investigate the value of prostate health index (PHI) in the diagnosis of prostate cancer in patients with total prostate specific antigen (tPSA) <20 μg/L. Methods: Totally 1 135 patients with tPSA<20 μg/L and prostate biopsy indications at Department of Urology, Fudan University Shanghai Cancer Center from March 2013 to April 2016 were enrolled in this study. They were tested for serum tPSA, free prostate specific antigen and prostate specific antigen isoform 2, from which PHI was calculated. Diagnostic efficacy of PHI and tPSA were evaluated using receiver operating characteristic (ROC) curve analysis. The detection rates of prostate cancer were calculated in different ranges of PHI. Subgroup analysis of 716 patients, who were aged 50 or above with tPSA in the range of 4 to 10 μg/L and digital rectal examination negative, was performed. Results: In the biopsied objects with tPSA<20 μg/L, PHI was significantly higher in prostate cancer patients than that in non-cancer patients (48.4(37.4) vs. 26.5(16.9), U=52 674.00, P=0.000), PHI was also significantly higher in high-grade prostate cancer patients than that of low-grade prostate cancer patients (44.5(30.8) vs. 56.4(42.5), U=23 314.00, P=0.000). The area under the curve (AUC) of PHI for diagnosing prostate cancer was significantly higher than that of tPSA (0.771 vs. 0.627, P=0.000). When PHI was in the range of <27, 27 to <36, 36 to <55 and ≥55, the probability of prostate cancer was 9.4% (95%CI: 7.0% to 12.2%), 16.3% (95%CI: 12.2% to 20.8%), 31.0% (95%CI: 25.9% to 37.3%) and 66.4% (95%CI: 58.9% to 74.2%), respectively. Subgroup analysis showed that the AUC of PHI in diagnosing prostate cancer was significantly higher than that of tPSA (0.764 vs. 0.569, P=0.000). When PHI was in the range of <27, 27 to <36, 36 to <55 and ≥55, the probability of prostate cancer was 8.1% (95%CI: 5.4% to 11.3%), 14.0% (95%CI: 9.1% to 19.9%), 30.8% (95%CI: 23.6% to 38.7%) and 78.8% (95%CI: 66.7% to 88.9%), respectively. Conclusion: PHI is superior to tPSA in the diagnosis of prostate cancer in Chinese men with tPSA<20 μg/L.

Assessment of free-hand transperineal targeted prostate biopsy using multiparametric magnetic resonance imaging-transrectal ultrasound fusion in Chinese men with prior negative biopsy and elevated prostate-specific antigen

BackgroundTo evaluate the role of free-hand transperineal targeted prostate biopsy using multiparametric magnetic resonance imaging-transrectal ultrasound (mpMRI-TRUS) fusion in Chinese men with repeated biopsy.MethodsA total of 101 consecutive patients suspicious of prostate cancer (PCa) at the mpMRI scan and with prior negative biopsy and elevated PSA values were prospectively recruited at two urological centers. Suspicious areas on mpMRI were defined and graded using PI-RADS score. Targeted biopsies (TB) were performed for each suspicious lesion and followed a 12-core systematic biopsy (SB). Results of biopsy pathology and whole-gland pathology at prostatectomy were analyzed and compared between TB and SB. The risk for biopsy positivity was assessed by univariate and multivariate logistic regression analysis.ResultsFusion biopsy revealed PCa in 41 of 101 men (40.6%) and 25 (24.8%) were clinically significant. There was exact agreement between TB and SB in 74 (73.3%) men. TB diagnosed 36% more significant cancer than SB (22 vs 13 cases, P = 0.012). When TB were combined with SB, an additional 14 cases (34.1%) of mostly significant PCa (71.4%) were diagnosed (P = 0.036). TB had greater sensitivity and accuracy for significant cancer than SB in 26 men with whole-gland pathology after prostatectomy. PI-RADS score on mpMRI was the most powerful predictor of PCa and significant cancer.ConclusionsFree-hand transperineal TB guided with MRI-TRUS fusion imaging improves detection of clinical significant PCa in Chinese men with previously negative biopsy. PI-RADS score is a reliable predictor of PCa and significant cancer.

Gene polymorphisms in the PI3K/AKT/mTOR signaling pathway contribute to prostate cancer susceptibility in Chinese men

In this hospital-based case-control study of 413 prostate cancer (PCa) cases and 807 cancer-free controls, we investigated the role of functional single nucleotide polymorphisms (SNPs) of pivotal genes in the PI3K/AKT/mTOR pathway. We genotyped 17 SNPs in mTOR, Raptor, AKT1, AKT2, PTEN, and K-ras and found that 4 were associated with PCa susceptibility. Among the variants, the homozygote variant CC genotype of mTOR rs17036508 C>T were associated with higher PCa risk than the wild TT genotypes (adjusted OR = 3.73 (95% CI = 1.75-7.94), P = 0.001). The GT genotype of mTOR rs2295080 G>T was more protective than the TT genotypes (adjusted OR=0.54 (95% CI=0.32-0.91), P=0.020). The distributions of Raptor rs1468033 A>G genotypes differed between cases and controls, especially in subgroups defined by age, BMI, smoking status, and ethnicity. The CT/CC genotypes of AKT2 rs7250897 C>T were associated with an increased risk of PCa, particularly in subgroups of age >71 and BMI >24 kg/m2. These findings suggest that SNPs in the PI3K/AKT/mTOR pathway may contribute to the risk of PCa in Chinese men.

Relationship of oestrogen receptor alpha gene polymorphisms with risk for benign prostatic hyperplasia and prostate cancer in Chinese men

The relationship of oestrogen receptor with benign prostatic hyperplasia (BPH) and prostate cancer (PC) is not clear at present. This study aimed to investigate the molecular mechanism underlying the occurrence and development of BPH and prostate.Two hundred forty-four PC cases, 260 BPH patients, and 222 healthy men were recruited from Han people in China, and the oestrogen receptor alpha (ESRα) gene polymorphism (rs2234693 [PvuII] and rs9340799 [XbaI]) on intron 1 was determined. The relationship of gene polymorphism with PC and BPH was evaluated with Logistic regression, and the linkage disequilibrium and haplotyping were assessed with SHEsis software.The risk for PC in BPH patients with PvuII C allele was higher (OR = 1.437, 95% CI: 1.110–1.859), but the differentiation degree of cancer cells was relatively better in PC patients with PvuII C allele (OR = 0.419, 95% CI: 0.285–0.616), and most of them are circumscribed (OR = 0.706, 95% CI: 0.485–1.02). There was significant linkage disequilibrium between PvuII and XbaI. The genotype TTAG not only induced BPH (OR = 6.260, 95% CI: 1.407–27.852), but increased the risk for PC (OR = 6.696, 95% CI: 1.504–29.801). However, the genotype TTAG in BPH patients had no relationship with the risk for PC (P > 0.05). Furthermore, men with haplotype TG were more likely to suffer PC (OR = 9.168, 95% CI: 2.393–35.119), but men with haplotype TA and enlarged prostate had a low risk for PC (OR = 0.708, 95% CI: 0.551–0.912).These results show the relationship between ESRα gene polymorphism and susceptibility to PC and BPH in Chinese men, and the ethnic and regional difference as well.

Prognostic significance of fibroblast growth factor receptor 4 polymorphisms on biochemical recurrence after radical prostatectomy in a Chinese population.

Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane receptor with ligand-induced tyrosine kinase activity and is involved in various biological and pathological processes. Several polymorphisms of FGFR4 are associated with the incidence and mortality of numerous cancers, including prostate cancer. In this study, we investigated whether the polymorphisms of FGFR4 influence the biochemical recurrence of prostate cancer in Chinese men after radical prostatectomy. Three common polymorphisms (rs1966265, rs2011077, and rs351855) of FGFR4 were genotyped from 346 patients with prostate cancer by using the Sequenom MassARRAY system. Kaplan–Meier curves and Cox proportional hazard models were used for survival analysis. Results showed biochemical recurrence (BCR) free survival was significantly affected by the genotypes of rs351855 but not influenced by rs1966265 and rs2011077. After adjusting for other variables in multivariable analysis, patients with rs351855 AA/AG genotypes showed significantly worse BCR-free survival than those with the GG genotype (HR = 1.873; 95% CI, 1.209–2.901; P = 0.005). Hence, FGFR4 rs351855 could be a novel independent prognostic factor of BCR after radical prostatectomy in the Chinese population. This functional polymorphism may also provide a basis for surveillance programs. Additional large-scale studies must be performed to validate the significance of this polymorphism in prostate cancer.

Prostate Specific Antigen and Prostate Cancer in Chinese Men Undergoing Initial Prostate Biopsies Compared with Western Cohorts

We determined the characteristics of Chinese men undergoing initial prostate biopsy and evaluated the relationship between prostate specific antigen levels and prostate cancer/high grade prostate cancer detection in a large Chinese multicenter cohort. This retrospective study included 13,904 urology outpatients who had undergone biopsy for the indications of prostate specific antigen greater than 4.0 ng/ml or prostate specific antigen less than 4.0 ng/ml but with abnormal digital rectal examination results. The prostate specific antigen measurements were performed in accordance with the standard procedures at the respective institutions. The type of assay used was documented and recalibrated to the WHO standard. The incidence of prostate cancer and high grade prostate cancer was lower in the Chinese cohort than the Western cohorts at any given prostate specific antigen level. Around 25% of patients with a prostate specific antigen of 4.0 to 10.0 ng/ml were found to have prostate cancer compared to approximately 40% in U.S. clinical practice. Moreover, the risk curves were generally flatter than those of the Western cohorts, that is risk did not increase as rapidly with higher prostate specific antigen. The relationship between prostate specific antigen and prostate cancer risk differs importantly between Chinese and Western populations, with an overall lower risk in the Chinese cohort. Further research should explore whether environmental or genetic differences explain these findings or whether they result from unmeasured differences in screening or benign prostate disease. Caution is required for the implementation of prostate cancer clinical decision rules or prediction models for men in China or other Asian countries with similar genetic and environmental backgrounds.

AB189. Prevalence and risk factors of prostate cancer in Chinese men with PSA 4–10 ng/mL underwent TRUS-guided prostate biopsy: the utilization of PAMD score

ObjectiveTo elucidate the characteristics and risk factors for positive biopsy outcomes in Chinese patients with prostate specific antigen (PSA) 4–10 ng/mL, and develop a risk-stratification score model.MethodsThe data of 345 patients underwent transrectal ultrasound-guided prostate biopsy between 2011 and 2013 was retrospectively analyzed. Digital rectal examination (DRE), prostate volum (PV), magnetic resonance imaging (MRI) and smoking status were also collected. Positive biopsy outcomes were defined as prostate cancer (PCa) and high grade PCa (HGPCa, Gleason Score ≥Th.ResultsThe median PSA was 7.15 (IQR 5.91–8.45) ng/mL. Overall 138 patients (40.0%) were shown to have PCa, including 100 patients (29.0%) with HGPCa. Smaller PV, elder age, MRI results and positive DRE were proved to be predictive factors for positive biopsy outcomes in both univariate and multivariate analysis. We developed a “PAMD” score which combined the four factors to category patients into three risk groups, and the model performed good predictive sensitivity and specificity.ConclusionsThe prevalence of prostate cancer in Chinese patients with PSA 4–10 ng/mL was 40%, including 29% patients with high grade disease. DRE, age, MRI and PV were predictive factors for positive biopsy outcomes, and the PAMD score model could be utilized for risk-stratification and decision-making.

The Cumulative Effect of Gene-Gene and Gene-Environment Interactions on the Risk of Prostate Cancer in Chinese Men.

Prostate cancer (PCa) is a multifactorial disease involving complex genetic and environmental factors interactions. Gene-gene and gene-environment interactions associated with PCa in Chinese men are less studied. We explored the association between 36 SNPs and PCa in 574 subjects from northern China. Body mass index (BMI), smoking, and alcohol consumption were determined through self-administered questionnaires in 134 PCa patients. Then gene-gene and gene-environment interactions among the PCa-associated SNPs were analyzed using the generalized multifactor dimensionality reduction (GMDR) and logistic regression methods. Allelic and genotypic association analyses showed that six variants were associated with PCa and the cumulative effect suggested men who carried any combination of 1, 2, or ≥3 risk genotypes had a gradually increased PCa risk (odds ratios (ORs) = 1.79–4.41). GMDR analysis identified the best gene-gene interaction model with scores of 10 for both the cross-validation consistency and sign tests. For gene-environment interactions, rs6983561 CC and rs16901966 GG in individuals with a BMI ≥ 28 had ORs of 7.66 (p = 0.032) and 5.33 (p = 0.046), respectively. rs7679673 CC + CA and rs12653946 TT in individuals that smoked had ORs of 2.77 (p = 0.007) and 3.11 (p = 0.024), respectively. rs7679673 CC in individuals that consumed alcohol had an OR of 4.37 (p = 0.041). These results suggest that polymorphisms, either individually or by interacting with other genes or environmental factors, contribute to an increased risk of PCa.

The older the better: The characteristic of localized prostate cancer in Chinese men

ObjectiveTo assess the clinicopathological features and overall survival between two groups of Chinese patients older or younger than 70 years after retropubic radical prostatectomy. MethodsFrom January 2001 to February 2010, 390 patients receive dretropubic radical prostatectomy. After excluding 89 patients with adjuvant or neoadjuvant hormonal therapy or radiotherapy, a total of 301 patients were included in this study. We arbitrarily divided these patients into younger age group (<70 years, 140 cases, 46.5%) and older age group (≥70 years, 161 cases, 53.5%). The differences in serum prostate specific antigen (PSA), Gleason score, clinical tumor stage, and biochemical-free survival were analyzed between the two groups. ResultsThere were not significant differences between the two groups in high Gleason score rate and clinical tumor stage. However, older patients had significantly lower biochemical recurrence rate than those of younger patients, and had significantly higher PSA levels. Multivariate analysis showed that older age, PSA level and clinical tumor stage were significantly associated with biochemical recurrence free survival. ConclusionIn Chinese men, older age (≥70 years) is associated with better outcome. If the physical condition permits, older age alone should not exclude patients from radical prostatectomy.

Higher body mass index increases the risk for biopsy-mediated detection of prostate cancer in Chinese men.

ObjectiveTo investigate the relationship between body mass index (BMI) and prostate cancer (PCa) risk at biopsy in Chinese men.Patients and MethodsWe retrospectively reviewed the records of 1,807 consecutive men who underwent initial multicore (≥10) prostate biopsy under transrectal ultrasound guidance between Dec 2004 and Feb 2014. BMI was categorised based on the Asian classification of obesity as follows: <18.5 (underweight), 18.5–22.9 (normal weight), 23–24.9 (overweight), 25–29.9 (moderately obese), and ≥30 kg/m2 (severely obese). The odds ratios (OR) of each BMI category for risk of PCa and high-grade prostate cancer (HGPCa, Gleason score ≥4+3) detection were estimated in crude, age-adjusted and multivariate-adjusted models. Prevalence ratios and accuracies of PSA predicted PCa were also estimated across BMI groups.ResultsIn total, PCa was detected by biopsy in 750 (45.4%) men, and HGPCa was detected in 419 (25.4%) men. Compared with men of normal weight, underweight men and obese men were older and had higher prostate specific antigen levels. The risk of overall PCa detection via biopsy presented an obvious U-shaped relationship with BMI in crude analysis. Overall, 50.0%, 37.4%, 45.6% 54.4% and 74.1% of the men in the underweight, normal weight, overweight, moderately obese and severely obese groups, respectively, were diagnosed with PCa via biopsy. In multivariate analysis, obesity was significantly correlated with a higher risk of PCa detection (OR = 1.17, 95%CI 1.10–1.25, P<0.001). However, higher BMI was not correlated with HGPCa detection (OR = 1.03, 95%CI 0.97–1.09, P = 0.29). There were no significant differences in the accuracy of using PSA to predict PCa or HGPCa detection across different BMI categories.ConclusionObesity was associated with higher risk of PCa detection in the present Chinese biopsy population. No significant association was detected between obesity and HGPCa.

Association of FOXP4 Gene with Prostate Cancer and the Cumulative Effects of rs4714476 and 8q24 in Chinese Men.

The tumor suppressor forkhead box P4 (FOXP4) plays important roles in oncogenesis, and the FOXP4 variant rs1983891 is associated with prostate cancer (PCa) in several studies. However, association studies conducted in Northern and Southern Chinese have provided conflicting results. Therefore, here we performed fine mapping of FOXP4 to identify the association with PCa and the potential application in Chinese men. We examined 11 variants spaced approximately 55 kb apart spanning FOXP4 using high-resolution melting-curve analysis and sequencing methods in 286 PCa patients and 630 controls, and the association between these variants and PCa risk was evaluated. Additionally, we evaluated the cumulative effect of rs4714476 and 2 variants in 8q24 (rs16901966, rs10090154) confirmed in our previous study. Of 11 SNPs, only rs4714476-C at the 5' near gene of FOXP4 was associated with increased age-adjusted PCa risk (p = 0.012, OR = 1.32, 95% CI = 1.06 - 1.63) and aggressive PCa (p = 0.026). The CG haplotype covering rs4714476-C demonstrated significant differences between PCa cases and controls (p = 0.009). The cumulative effect analysis showed men who carried any combination of 1, 2, or 3 risk genotypes had a gradually increased PCa risk (age-adjusted OR is from 1.244 to 3.312). These data suggest that rs4714476 at the 5' near gene of FOXP4 potentially contributes to the susceptibility of PCa in Chinese men. The cumulative effect of rs4714476 at FOXP4 and 8q24 could increase PCa risk.

Prevalence and Risk Factors of Prostate Cancer in Chinese Men with PSA 4-10 ng/mL Who Underwent TRUS-Guided Prostate Biopsy: The Utilization of PAMD Score.

Purpose. To elucidate the characteristics and risk factors for positive biopsy outcomes in Chinese patients with prostate specific antigen (PSA) 4–10 ng/mL and develop a risk-stratification score model. Methods. The data of 345 patients who underwent transrectal ultrasound-guided prostate biopsy between 2011 and 2013 was retrospectively analyzed. Digital rectal examination (DRE), prostate volume (PV), magnetic resonance imaging (MRI), and smoking status were also collected. Positive biopsy outcomes were defined as prostate cancer (PCa) and high grade PCa (HGPCa, Gleason Score ≥ 7). Results. The median PSA was 7.15 (IQR 5.91–8.45) ng/mL. Overall 138 patients (40.0%) were shown to have PCa, including 100 patients (29.0%) with HGPCa. Smaller PV, elder age, MRI results, and positive DRE were proved to be predictive factors for positive biopsy outcomes in both univariate and multivariate analysis. We developed a “PAMD” score which combined the four factors to categorize patients into three risk groups, and the model performed good predictive sensitivity and specificity. Conclusion. The prevalence of prostate cancer in Chinese patients with PSA 4–10 ng/mL was 40%, including 29% patients with high grade disease. DRE, age, MRI, and PV were predictive factors for positive biopsy outcomes, and the PAMD score model could be utilized for risk-stratification and decision-making.

Percent free prostate-specific antigen does not improve the effectiveness of prostate cancer detection in Chinese men with a prostate-specific antigen of 2.5–20.0 ng/ml: a multicenter study

The prostate-specific antigen (PSA) "gray zone" in Chinese men is likely higher than the traditional value (2.5-10.0 ng/ml) since the incidence of prostate cancer in Chinese men is relative low. The utility of percent free PSA in predicting prostate cancer is based on Western populations and may introduce sizable bias when applied to a Chinese cohort. We assessed the efficacy of percent free PSA in predicting prostate cancer in Chinese men with a PSA of 2.5-10.0 and 10.1-20.0 ng/ml. A total of 558 men with a PSA of 2.5-20.0 ng/ml who had undergone prostatic biopsy to detect prostate cancer from two Chinese centers were included. The rates of prostate cancer in different percent free PSA ranges were evaluated. Receiver operating characteristic curve (ROC) was used to evaluate and compare the efficiency of PSA and percent free PSA in the diagnosis of prostate cancer. The areas under ROC (AUCs) for percent free PSA for predicting prostate cancer were not higher than those for PSA, although prostate cancer detection rates increased with decreased percent free PSA in men with a PSA of 2.5-10.0, 10.1-20.0, and 2.5-20.0 ng/ml. Similarly, for men aged <70 and ≥ 70 years and with prostate volume <40 and ≥ 40 ml, AUCs showed percent free PSA was not better than PSA in predicting prostate cancer. By analyzing multicenter data, we first found that percent free PSA does not improve detection of prostate cancer in Chinese men with a PSA of 2.5-10.0 or 10.1-20.0 ng/ml.

Relationship between multidrug resistance 1 polymorphisms and the risk of prostate cancer in Chinese populations

Prostate cancer is one of the most common malignancies in men. The multidrug resistance 1 gene (MDR1) is an important candidate gene for prostate cancer. The aim of this study was to evaluate the association between MDR1 gene polymorphisms and the risk of prostate cancer. MDR1 gene polymorphism and its association with the risk of prostate cancer were investigated in 357 Chinese men. A novel c.1465C>T polymorphism was detected with created restriction site-polymerase chain reaction and DNA sequencing. We found a significantly increased risk of prostate cancer in the homozygote comparison [TT vs CC: odds ratio (OR) = 2.300, 95% confidence interval (95%CI) = 1.261-4.196, chi-square = 7.53, P = 0.007], heterozygote comparison (TC vs CC: OR = 1.667, 95%CI = 1.049-2.648, chi-square = 4.71, P = 0.030), dominant model (TT/TC vs CC: OR = 1.835, 95%CI = 1.197-2.815, chi-square = 7.81, P = 0.005), recessive model (TT vs OR = 1.776, 95%CI = 1.023- 3.085, chi-square = 4.23, P = 0.041), and allele contrast (T vs C: OR = 1.625, 95%CI = 1.199-2.202, chi-square = 9.87, P = 0.002). These findings suggested that the c.1465C>T polymorphism of MDR1 may be risk factors for prostate cancer in Chinese men.

Prostate-specific Antigen Velocity (PSAV) and PSAV per Initial Volume (PSAVD) for Early Detection of Prostate Cancer in Chinese Men

To investigate the utility of prostate-specific antigen velocity (PSAV) and PSAV per initial volume (PSAVD) for early detection of prostate cancer (PCa) in Chinese men. Between January 2009 and June 2012, a total of 193 men (aged 49-84 years, median 67 years) with at least 2 transrectal ultrasonography (TRUS) procedures and concurrent serum PSA measurements underwent prostate biopsy because of suspicion of PCa. The total group were classified into PCa and non-PCa groups, and the variables of the two groups were compared. Univariate and multivariate analyses were used to investigate which variables were predictove. The diagnostic values of PSAV, PSAVD and prostate-specific antigen density (PSAD) were compared using receiver operating characteristic (ROC) analysis. Prostate cancer was diagnosed in 44 (22.8%) of the 193 men. There were significant differences between the groups in last and initial prostate volumes determined by TRUS, initial age, last serum PSA levels, PSAV, PSAD and PSAVD. After adjusting for confounding factors, the odds ratios of PCa across the quartile of PSAVD were 1, 4.06, 10.6, and 18.9 (P for trend <0.001).The area under the ROC curves (AUCs) of PSAD (0.779) and PSAVD (0.776) were similar and both significantly greater than that of PSA (AUC 0.667). PSAVD was a significantly better indicator of PCa than PSAV (AUC 0.736). There was no statistical significant difference between the AUC of PSAV and that of last serum PSA level. The sensitivity and specificity of PSAVD at a cutoff of 0.023ng in participants with last serum PSA levels of 4.0 ng/mL-10.0 ng was 73.7% and 70.7%, respectively. The results of this study demonstrated PSAVD may be a useful tool in PCa detection, especially in those undergoing previous TRUS examination.

Outcomes and Trends of Prostate Biopsy for Prostate Cancer in Chinese Men from 2003 to 2011

BackgroundProstate-specific antigen (PSA) screening is growing in popularity in China, but its impact on biopsy characteristics and outcomes are poorly understood.ObjectiveOur objective was to characterize prostate biopsy outcomes and trends in Chinese men over a 10-year period, since the increasing use of PSA tests.MethodsAll men (n = 1,650) who underwent prostate biopsy for PCa at Huashan Hospital, Shanghai, China from 2003–2011 were evaluated. Demographic and clinical information was collected for each patient, including age, digital rectal examination (DRE), transrectal ultrasound (prostate volume and nodule), total prostate-specific antigen (tPSA) levels and free PSA ratio (fPSA/tPSA) prior to biopsy. Prostate biopsy was performed using six cores before October 2007 or ten cores thereafter. Logistic regression and multivariate analysis were used to evaluate our data.ResultsThe overall positive rate of prostate biopsy for PCa was 47% and the rate decreased significantly over the years from 74% in 2003 to 33% in 2011 (P-trend = 0.004) . Age at diagnosis was slightly increased (P-trend = 0.04) while fPSA/tPSA was significantly decreased (P-trend = 1.11×10-5). A statistically significant trend was not observed for tPSA levels, prostate volume, or proportion of positive nodule. The model including multiple demographic and clinical variables (i.e., age, DRE, tPSA, fPSA/tPSA and transrectal ultrasound results) (AUC = 0.93) statistically outperformed models that included only PSA (AUC = 0.85) or fPSA/tPSA (AUC = 0.66) to predict PCa risks (P<0.05). Similar results were observed in a subgroup of men whose tPSA levels were lower than 20 ng/mL (AUC = 0.87, vs. AUC of tPSA = 0.62, P<0.05).ConclusionsDetection rates of PCa and high-grade PCa among men that underwent prostate biopsy at the institution has decreased significantly in the past 10 years, likely due to increasing use of PSA tests. Predictive performance of demographic and clinical variables of PCa was excellent. These variables should be used in clinics to determine the need for prostate biopsy.