Individualized prostate biopsy strategy for Chinese patients with different prostate-specific antigen levels

Aim： To evaluate the best individualized prostate biopsy strategies for Chinese patients with suspected prostate cancer. Methods： The present study included 221 Chinese patients who underwent transrectal ultrasound guided prostate biopsies for the first time. All patients underwent the same 10-core biopsy protocol. In addition to the Hodge sextant technique, four more biopsies were obtained from the base and middle regions of bilateral peripheral zones. The differences between 10-core and sextant strategies in cancer detection among patients with different prostate specific anitgen （PSA） levels were evaluated. The relationship between PSA level, number of positive biopsy cores and organ-confined cancer rate in prostate cancer patients was also analyzed. Results： The overall prostate cancer detection rate was 40.7% in the 221 patients. The 10-core strategy increased cancer detection by 6.67% （6/90） in our patients （P 〈 0.05）. The increased cancer detection rates decreased significantly when the patient PSA level increased from 0-20 ng/mL to 20.1-50 ng/mL and 〉 50 ng/mL （P 〈 0.01）. The number of positive biopsy cores in prostate cancer patients increased significantly with increasing patient PSA level （P 〈 0.01）. The rate of organ-confined prostate cancer decreased significantly with increasing patient PSA level （P 〈 0.01）. Conclusion： The extended 10- core strategy is recommended for Chinese patients with PSA 〈 20 ng/mL and the sextant strategy is recommended for those with PSA〉 50 ng/mL. For patients with PSA ranging from 20.1 ng/mL to 50 ng/mL, the 10-core strategy should be applied in patients with life expectancy 〉 10 years and the sextant strategy should be applied in those with life expectancy 〈 10 years. （Asian J Androl 2008 Mar; 10： 325-331）

A nomogram to predict Gleason sum upgrading of clinically diagnosed localized prostate cancer among Chinese patients

Although several models have been developed to predict the probability of Gleason sum upgrading between biopsy and radical prostatectomy specimens,most of these models are restricted to prostatespecific antigen screening-detected prostate cancer.This study aimed to build a nomogram for the prediction of Gleason sum upgrading in clinically diagnosed prostate cancer.The study cohort comprised 269 Chinese prostate cancer patients who underwent prostate biopsy with a minimum of 10 cores and were subsequently treated with radical prostatectomy.Of all included patients,220(81.8%) were referred with clinical symptoms.The prostate-specific antigen level,primary and secondary biopsy Gleason scores,and clinical T category were used in a multivariate logistic regression model to predict the probability of Gleason sum upgrading.The developed nomogram was validated internally.Gleason sum upgrading was observed in 90(33.5%) patients.Our nomogram showed a bootstrap-corrected concordance index of 0.789 and good calibration using 4 readily available variables.The nomogram also demonstrated satisfactory statistical performance for predicting significant upgrading.External validation of the nomogram published by Chun et al.in our cohort showed a marked discordance between the observed and predicted probabilities of Gleason sum upgrading.In summary,a new nomogram to predict Gleason sum upgrading in clinically diagnosed prostate cancer was developed,and it demonstrated good statistical performance upon internal validation.

External validation of the Prostate Cancer Prevention Trial and the European Randomized Study of Screening for Prostate Cancer risk calculators in a Chinese cohort

Several prediction models have been developed to estimate the outcomes of prostate biopsies. Most of these tools were designed for use with Western populations and have not been validated across different ethnic groups. Therefore, we evaluated the predictive value of the Prostate Cancer Prevention Trial （PCPT） and the European Randomized Study of Screening for Prostate Cancer （ERSPC） risk calculators in a Chinese cohort. Clinicopathological information was obtained from 495 Chinese men who had undergone extended prostate biopsies between January 2009 and March 2011. The estimated probabilities of prostate cancer and high-grade disease （Gleason 〉6） were calculated using the PCPT and ERSPC risk calculators. Overall measures, discrimination, calibration and clinical usefulness were assessed for the model evaluation. Of these patients, 28.7% were diagnosed with prostate cancer and 19.4% had high-grade disease. Compared to the PCPT model and the prostate-specific antigen （PSA） threshold of 4 ng m1-1, the ERSPC risk calculator exhibited better discriminative ability for predicting positive biopsies and high-grade disease （the area under the curve was 0.831 and 0.852, respectively, P〈O.01 for both）. Decision curve analysis also suggested the favourable clinical utility of the ERSPC calculator in the validation dataset. Both prediction models demonstrated miscalibration： the risk of prostate cancer and high-grade disease was overestimated by approximately 20% for a wide range of predicted probabilities. In conclusion, the ERSPC risk calculator outperformed both the PCPT model and the PSA threshold of 4 ng ml- z in predicting prostate cancer and high-grade disease in Chinese patients. However, the prediction tools derived from Western men significantly overestimated the probability of prostate cancer and high-grade disease compared to the outcomes of biopsies in a Chinese cohort.

Prognostic factors in Chinese patients with metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy

This study aims to evaluate the potential value of patient characteristics in predicting overall survival （OS） in patients with metastatic castration-resistant prostate cancer （mCRPC） treated with docetaxel-based thermotherapy. A total of 115 patients with mCRPC undergoing a docetaxel q3w regimen were enrolled in this study. A survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the prognostic value of all covariates for OS. OS was also analysed after stratifying patients according to the results of multivariate analysis. The median OS for the entire cohort was 17.0 months. The multivariate analysis showed that the prostate-specific antigen doubling time （PSADT）, baseline haemoglobin （Hb） concentration, alkaline phosphatase （ALP） concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS. According to the presence of PSADT 〈46.3 days and baseline ALP/〉 110 IU 1-1, all patients were divided into three risk groups： low-risk group （no risk factors）, intermediate-risk group （one risk factor） and high-risk group （two risk factors）. Median OSs for patients in low-, intermediate- and high-risk groups were 28.0 months （95% Ch 23.8-32.2）, 21.0 months （95% Ch 18.9-23.1） and 11.0 months （95% Ch 7.6-14.4）, respectively （P〈O.O01）. In conclusion, PSADT, baseline Hb concentration, ALP concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS in Chinese patients with mCRPC treated with docetaxel. PSADT combined with the baseline ALP concentration could be a useful risk stratification parameter for evaluating survival outcomes.

Prostate-specific antigen half-life： a new predictor of progression- free survival and overall survival in Chinese prostate cancer patients

We investigated the potential value of prostate-specific antigen half-life （PSAHL） and decreasing velocity （PSAVd） to predict progression-free survival （PFS） and overall survival （OS） in Chinese patients with prostate cancer. A total of 153 patients treated with hormonal therapy were included in the study. Of these, 78 patients progressed to hormone- refractory prostate cancer （HRPC） and 24 patients died by the end of follow-up. PSAHL was defined as the time during which prostate-specific antigen （PSA） concentration became half of the initial value during the first hormonal therapy. PSAVd reflected the decreasing velocity of PSA during the first hormonal therapy. PFS was defined as the interval from the beginning of hormonal therapy to HRPC. Cox proportional hazards regression analysis was used to evaluate whether PSAHL and PSAVd were significantly associated with PFS and OS. The median PSAHL and PSAVd were 0.50 months and 33.8 ng mL^-1 per month. The median PFS and OS were 22.7 months （95% confidence interval [CI], 22.0-29.6 months） and 43.5 months （95% CI, 37.9-48.4 months）, respectively. On univariate and multivariate analysis, long PSAHL （〉 0.5 months）, metastatic disease, high biopsy Gleason scores （〉 8） and high nadir PSA （〉 0.4 ng mL^-1） were all found to be significantly associated with short PFS. Long PSAHL, high nadir PSA and short PSA doubling time （PSADT 〈 2.0 months） were significantly associated with short OS. There were no significant relationships between PSAVd and either PFS or OS. Thus, PSAHL is a promising new independent predictor of survival. Patients with long PSAHL were identified as those at high risk for a relatively short PFS and OS.

Influence of obesity on localized prostate cancer patients Ireated with radical prostatectomy

This study aimed to investigate the association between different anthropometric measures of obesity and clinicopathological characteristics in Chinese patients with clinically localized prostate cancer （PCa）. A total of 734 patients with clinically localized PCa who underwent radical prostatectomy （RP） were included in this study. Clinical and pathological data from each patient were collected. Anthropometric measures of abdominal adiposity were measured from T2-weighted sagittal Iocalisation images from magnetic resonance imaging （MRI） for 413 （56.3%） patients. Patient clinical and pathological characteristics were compared across body mass index （BMI） groups. Univariable and multivariable logistic regression models were used to address the influence of the preoperative total testosterone level and anthropometric measures of obesity on pathological outcomes. In the multivariate analysis, BMI was not significantly associated with any pathological outcomes. However, the percentage of visceral adipose tissue （VAT%） was an independent predictor of a pathological Gleason score ≥8 （P〈0.O01）, extracapsular extension （ECE; P=0.002） and seminal vesicle invasion （SVI; P=0.007）. More importantly, we found that the preoperative total testosterone level was significantly correlated with the VAT% （Pearson＇s correlation coefficient： -0.485, P〈0.001） and subcutaneous adipose tissue （SAT; Pearson＇s correlation coefficient： 0.413, P〈0.001）. In conclusion, the results of this study suggest that abdominal fat distribution, and particularly VAT%, is associated with a risk of advanced PCa. Moreover, our present study confirms a significant inverse correlation between visceral adiposity and testosterone. Further studies are warranted to elucidate the biological mechanisms underlying the relationship between abdominal adiposity and the aggressiveness of PCa.

Lymph Node Metastases and Prognosis in Penile Cancer

Lymph node status is a key prognostic factor in penile squamous cell carcinoma. Recently, growing evidence indicates a multimodality approach consisting of neoadjuvant chemotherapy followed by consolidation surgery improves the outcome of locally advanced penile cancer. Thus, accurate estimation of survival probability in node-positive penile cancer is critical for treatment decision making, counseling of patients and follow-up scheduling. This article reviewed evolving developments in assessing the risk for cancer progression based on lymph node related variables, such as the number of metastatic lymph nodes, bilateral lymph node metastases, the ratio of positive lymph nodes, extracapsular extension of metastatic lymph nodes, pelvic lymph node metastases, metastatic deposit in sentinel lymph nodes and N stage in TNM classification. Controversial issues surrounding the prognostic value of these nodal related predictors were also discussed.

Perioperative complications of radical retropubic prostatectomy in patients with locally advanced prostate cancer： a comparison with clinically localized prostate cancer

Radical prostatectomy （RP） continues to be an effective surgical therapy for prostate carcinoma, particularly for organ-confined prostate cancer （PCa）. Recently, RP has also been used in the treatment of locally advanced prostate cancer. However, little research has been performed to elucidate the perioperative complications associated with RP in patients with clinically localized or locally advanced PCa. We sought to analyse the incidence of complications in these two groups after radical retropubic prostatectomy （RRP）. From June 2002 to July 2010, we reviewed 379 PCa patients who underwent RRP in our hospital. Among these cases, 196 had clinically localized PCa （Tla-T2c group 1）, and 183 had locally advanced PCa （ ≥ T3,： group 2）. The overall complication incidence was 21.9%, which was lower than other studies have reported. Perioperative complications in patients with locally advanced PCa mirror those in patients with clinically localized PCa （26.2% vs. 17.8%, P=0.91）. Our results showed that perioperative complications could not be regarded as a factor to consider in regarding RP in patients with cT3 or greater.

Human epidermal growth factor receptor type 2 protein expression in Chinese metastatic prostate cancer patients correlates with cancer specific survival and increases after exposure to hormonal therapy

Aim： To investigate human epidermal growth factor receptor type 2 （HER2） protein expression and gene amplification in Chinese metastatic prostate cancer patients and their potential value as prognostic factors. Methods： Immunohistochemistry （IHC） was performed to investigate HER2 protein expression in prostate biopsy specimens from 104 Chinese metastatic prostate cancer patients. After 3-11 months of hormonal therapy, 12 patients underwent transurethral resection of the prostate （TURP）. HER2 protein expression of TURP specimens was compared with that of the original biopsy specimens. Of these, 10 biopsy and 4 TURP specimens with HER2 IHC staining scores ≥ 2＋ were investigated for HER2 gene amplification status by fluorescent in situ hybridization （FISH）. Results： Of the 104 prostate biopsy specimens, HER2 protein expression was 0, 1＋, 2＋ and 3＋ in 49 （47.1%）, 45 （43.3%）, 8 （7.7%） and 2 （1.9%） cases, respectively. There was a significant association between HER2 expression and Gleason score （P = 0.026）. HER2 protein expression of prostate cancer tissues increased in 33.3% of patients after hormonal therapy. None of the 14 specimens with HER2 IHC scores 〉 2＋ showed HER2 gene amplification. Patients with HER2 scores 〉 2＋ had a significantly higher chance of dying from prostate cancer than those with HER2 scores of 0 （P = 0.004） and 1＋ （P = 0.034）. Multivariate Cox regression analysis showed that HER2 protein expression intensity was an independent predictor of cancer-related death （P = 0.039）. Conclusion： An HER2 IHC score 〉 2＋ should be defined as HER2 protein overexpression in prostate cancer. Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer. HER2 protein expression increases in some individual patients after hormonal therapy.

External validation of nomograms for predicting cancer-specific mortality in penile cancer patients treated with definitive surgery

Using a population-based cancer registry,Thuret et al.developed 3 nomograms for estimating cancerspecific mortality in men with penile squamous cell carcinoma.In the initial cohort,only 23.0% of the patients were treated with inguinal lymphadenectomy and had pN stage.To generalize the prediction models in clinical practice,we evaluated the performance of the 3 nomograms in a series of penile cancer patients who were treated with definitive surgery.Clinicopathologic information was obtained from 160 M0 penile cancer patients who underwent primary tumor excision and regional lymphadenectomy between 1990 and 2008.The predicted probabilities of cancer-specific mortality were calculated from 3 nomograms that were based on different disease stage definitions and tumor grade.Discrimination,calibration,and clinical usefulness were assessed to compare model performance.The discrimination ability was similar in nomograms using the TNM classification or American Joint Committee on Cancer staging(Harrell's concordance index = 0.817 and 0.832,respectively),whereas it was inferior for the Surveillance,Epidemiology and End Results staging(Harrell's concordance index = 0.728).Better agreement with the observed cancer-specific mortality was shown for the model consisting of TNM classification and tumor grade,which also achieved favorable clinical net benefit,with a threshold probability in the range of 0 to 42%.The nomogram consisting of TNM classification and tumor grading was shown to have better performance for predicting cancer-specific mortality in penile cancer patients who underwent definitive surgery.Our data support the integration of this model in decision-making and trial design.

The effectiveness of the TAX 327 nomogram in predicting overall survival in Chinese patients with metastatic castration-resistant prostate cancer

Based on the results of TAX 327, a nomogram was developed to predict the overall survival of metastatic castration-resistant prostate cancer （mCRPC） after first-line chemotherapy. The nomogram, however, has not been validated in an independent dataset, especially in a series out of clinical trials. Thus, the objective of the current study was to validate the TAX 327 nomogram in a community setting in China. A total of 146 patients with mCRPC who received first-line chemotherapy （docetaxel or mitoxantrone） were identified. Because clinical trials are limited in China's Mainland, those patients did not receive investigational treatment after the failure of first-line chemotherapy. The predicted overall survival rate was calculated from the TAX 327 nomogram. The validity of the model was assessed with discrimination, calibration and decision curve analysis. The median survival of the cohort was 21 months （docetaxel） and 19 months （mitoxantrone） at last follow-up. The predictive c-index of the TAX 327 nomogram was 0.66 （95% CI： 0.54-0.70）. The calibration plot demonstrated that the 2-year survival rate was underestimated by the nomogram. Decision curve analysis showed a net benefit of the nomogram at a threshold probability greater than 30%. In conclusion, the present validation study did not confirm the predictive value of the TAX 327 nomogram in a contemporary community series of men in China, and further studies with a large sample size to develop or validate nomograms for predicting survival and selecting therapies in advanced prostate cancer are necessary.

Early prostate specific antigen decline and its velocity are independent predictive factors for outcomes of mCRPC patients treated with abiraterone acetate

Dear Editor,Although the incidence of prostate cancer(PCa) has decreased in recent decades in Western countries, it has gradually increased in China due to the increasingly longer life expectancy and more popular westernized diet[1].

The prognostic factors of effective ketoconazole treatment for metastatic castration-resistant prostate cancer： who can benefit from ketoconazole therapy？

We investigated the prognostic value of some variables of effective ketoconazole treatment for metastatic castration-resistant prostate cancer （mCRPC）. In total, 163 patients with mCRPC were eligible, receiving ketoconazole 200-400 mg three times daily with replacement doses of prednisone. Progression-free survival （PFS） was calculated from the beginning of the ketoconazole therapy to the onset of disease progression. The prognostic value of different variables for PFS was assessed by Cox regression analysis. The median PFS was 2.6 months （0.5-8.6 months） for these patients. The serum testosterone level changed during therapy, which decreased when the prostate-specific antigen （PSA） declined; the serum testosterone level increased as the levels of PSA relapsed. The median PFS values for patients associated with different factors were the following： 1.4 and 3.5 months for a nadir PSA of ≥ 0.2 and 〈0.2 ng ml- 1, respectively （hazard rate （HR）=4.767, P〈0.001）; 3.1 and 1.6 months for a baseline testosterone of ≥0.1 and 〈0.1 ng m1-1, respectively （HR=2.865, P=0.012）; 2.8 and 1.9 months for a baseline haemoglobin of ≥ 120 and 〈120 g 1-1, respectively （HR= 1.605, P〈0.001）; and 3.0 and 1.9 months for a PSA doubling time （PSADT） of ≥ 2.0 and 〈2.0 months, respectively （HR= 1.454, P=-0.017）. A risk model was constructed according to the four factors that divided patients into three subgroups of low risk （0-1 factors）, moderate risk （2 factors） and high risk （3-4 factors） with PFS values of 3.6, 3.0 and 1.4 months, respectively （HR=1.619, P〈0.001）. A nadir PSA of ≥0.2 ng m1-1, a baseline testosterone of 〈0.1 ng m1-1, a baseline haemoglobin of 〈 120 g I- 1 and a PSADT of 〈2 months were associated with a poor PFS. This risk model could provide evidence to predict the survival benefit of ketoconazole therapy.

Network meta-analysis of combination strategies in metastatic hormone-sensitive prostate cancer

This study compared different doublet and triplet therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer(mHSPC).PubMed,EMBASE,and the Cochrane Library were comprehensively searched for eligible randomized controlled trials(RCTs)published from inception to October 2023.Interventions included abiraterone,apalutamide,enzalutamide,docetaxel,darolutamide,and androgen deprivation therapy(ADT),either as doublet or triplet therapies.The outcomes examined were overall survival(OS),progression-free survival(PFS),castration-resistant prostate cancer(CRPC)-free survival,time to symptomatic skeletal event(SSE),and toxicity.The surface under the cumulative ranking curve(SUCRA)was determined to identify the preferred treatments.Ten RCTs were included.The combination of darolutamide,docetaxel,and ADT had the highest SUCRA of 84.3 for OS,followed by combined abiraterone,docetaxel,and ADT(SUCRA=71.6).The highest SUCRAs for PFS were observed for triplet therapies(abiraterone,docetaxel,and ADT[SUCRA=74.9],followed by enzalutamide,docetaxel,and ADT[SUCRA=74.3])and other androgen receptor axis-targeted therapy-based doublet therapies(SUCRAs:26.5–59.3).Darolutamide,docetaxel,and ADT had the highest SUCRAs,i.e.,80.8 and 84.0 regarding CRPC-free survival and time to SSE,respectively.Regarding Grade>3 adverse events(AEs),the SUCRAs of triplet therapies(SUCRAs:14.8–31.5)were similar to that of docetaxel and ADT(SUCRA=39.5).Three studies had a low risk of bias in all categories;the remaining studies had at least an unclear risk of bias in at least one category.Triplet therapy demonstrated potentially enhanced effectiveness than doublet therapy in mHSPC,with acceptable safety concerns.Darolutamide might be the optimal option for triplet therapy in combination with docetaxel and ADT.

Apalutamide for metastatic castration-sensitive prostate cancer:final analysis of the Asian subpopulation in the TITAN trial

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial showed improvement in overall survival(OS)and other efficacy endpoints with apalutamide plus androgen deprivation therapy(ADT)versus ADT alone in patients with metastatic castration-sensitive prostate cancer(mCSPC).As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer,a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation.Event-driven endpoints were OS,and time from randomization to initiation of castration resistance,prostate-specific antigen(PSA)progression,and second progression-free survival(PFS2)on first subsequent therapy or death.Efficacy endpoints were assessed using the Kaplan–Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity.Participating Asian patients received once-daily apalutamide 240 mg(n=111)or placebo(n=110)plus ADT.After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide,apalutamide reduced the risk of death by 32%(hazard ratio[HR]:0.68;95%confidence interval[CI]:0.42–1.13),risk of castration resistance by 69%(HR:0.31;95%CI:0.21–0.46),PSA progression by 79%(HR:0.21;95%CI:0.13–0.35)and PFS2 by 24%(HR:0.76;95%CI:0.44–1.29)relative to placebo.The outcomes were comparable between subgroups with low-and high-volume disease at baseline.No new safety issues were identified.Apalutamide provides valuable clinical benefits to Asian patients with mCSPC,with an efficacy and safety profile consistent with that in the overall patient population.

Relationships of body composition and adipocytokines with outcomes in metastatic castration-resistant prostate cancer patients receiving docetaxel chemotherapy

We evaluated the relationships of body composition and serum adipocytokine levels with progression-free survival(PFS)and overall survival(OS)in metastatic castration-resistant prostate cancer(mCRPC)patients receiving docetaxel.The medical records of mCRPC patients who received docetaxel between January 2011 and December 2015 at Fudan University Shanghai Cancer Center(Shanghai,China)were reviewed.The following body composition parameters were calculated using computed tomography:skeletal muscle index(SMI),visceral adipose tissue index(VATI),and subcutaneous adipose tissue index(SATI).Pretreatment serum adipocytokine levels,including interleukin 6,insulin,leptin,monocyte chemoattractant protein-1,adiponectin,and resistin,were measured using the multiplex bead-based immunoassays.Cox regression and Kaplan–Meier methods were used for survival analyses.Of the 453 mCRPC patients initially identified,105 were included in the analysis.High VATI group patients had longer PFS(median,10 months vs 7 months,P=0.008)and OS(median,24 months vs 15 months,P=0.017),compared with low VATI group patients.SMI and SATI were not significantly associated with PFS or OS.Of the six detected adipocytokines,only leptin was associated with mCRPC prognosis.High leptin group patients had shorter PFS(median,7 months vs 12 months,P=0.0018)and OS(median,17 months vs 22 months,P=0.042),compared with low leptin group patients.Multivariate analysis showed that a high VATI was an independent protective factor for PFS and OS,while a high leptin level was an independent risk factor for PFS and OS.Therefore,VATI and serum leptin levels could provide important information concerning mCRPC prognosis.

Percent free prostate-specific antigen is effective to predict prostate biopsy outcome in Chinese men with prostate-specific antigen between 10.1 and 20.0 ng ml^-1

Percent free prostatic-specific antigen （%fPSA） has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml^-1, however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml^-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer （PCa） and high-grade PCa （HGPCa） was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA〉4.0 ng ml^-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA （%fPSA ＋ PSA） was determined by the area under the receivers operating characteristic curve （AUC）. %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1.

Performance of the Prostate Health Index in predicting prostate biopsy outcomes among men with a negative digital rectal examination and transrectal ultrasonography

The [-2]proPSA （p2PSA） and its derivatives, the p2PSA-to-free PSA ratio （%p2PSA）, and the Prostate Health Index （PHI） have greatly improved discrimination between men with and without prostate cancer （PCa） in prostate biopsies. However, little is known about their performance in cases where a digital rectal examination （DRE） and transrectal ultrasonography （TRUS） are negative. A prospective cohort of 261 consecutive patients in China with negative DRE and TRUS were recruited and underwent prostate biopsies. A serum sample had collected before the biopsy was used to measure various PSA derivatives, including total prostate-specific antigen （tPSA）, free PSA, and p2PSA. For each patient, the free-to-total PSA ratio （%fPSA）, PSA density （PSAD）, p2PSA-to-free PSA ratio （%p2PSA）, and PHI were calculated. Discriminative performance was assessed using the area under the receiver operating characteristic curve （AUC） and the biopsy rate at 91% sensitivity. The AUC scores within the entire cohort with respect to age, tPSA, %fPSA, PSAD, p2PSA, %p2PSA, and PHI were 0.598, 0.751, 0.646, 0.789, 0.814, 0.808, and 0.853, respectively. PHI was the best predictor of prostate biopsy results, especially in patients with a tPSA of 10.1-20 ng ml-1. Compared with other markers, at a sensitivity of 91%, PHI was the most useful for determining which men did not need to undergo biopsy, thereby avoiding unnecessary procedures. The use of PHI could improve the accuracy of PCa detection by predicting prostate biopsy outcomes among men with a negative DRE and TRUS in China.

Relationship between circumcision and human papillomavirus infection： a systematic review and meta-analysis

Male circumcision （MC） is reported to reduce human papillomavirus （HPV） prevalence in men. However, the efficacy remains imprecise. The aim of this study was to conduct a systematic review and meta-analysis to assess the relationship between MC and genital HPV infection and genital warts. PUBMED, EMBASE, and Web of Science were searched from inception to March 22, 2015. We identified 30 papers, including a total of 12149 circumcised and 12252 uncircumcised men who were evaluated for the association of circumcision with genital HPV or genital warts. Compared with men who were not circumcised, circumcised men may have had significantly reduced odds of genital HPV prevalence （odds ratio [OR]： 0.68; 95% confidence interval [95% CI]： 0.56-0.82）. There was no significant association between MC and genital HPV acquisition of new infections （OR： 0.99; 95% CI： 0.62-1.60）, genital HPV clearance （OR： 1.38; 95% Ch 0.96-1.97）, and prevalence of genital warts （OR： 1.17; 95% CI： 0.63-2.17）. This meta-analysis suggests that circumcision reduces the prevalence of genital HPV infections. However, no clear evidence was found that circumcision was associated with decreased HPV acquisition, increased HPV clearance, or decreased the prevalence of genital warts. More studies are required to evaluate adequately the effect of MC on the acquisition and clearance of HPV infections and prevalence of genital warts.

Phi-based risk calculators performed better in the prediction of prostate cancer in the Chinese population

Risk prediction models including the Prostate Health Index(phi)for prostate cancer have been well established and evaluated in the Western population.The aim of this study is to build phi-based risk calculators in a prostate biopsy population and evaluate their performanee in predicting prostate cancer(PCa)and high-grade PCa(Gleason score 27)in the Chinese population.We developed risk calculators based on 635 men who underwent initial prostate biopsy.Then,we validated the performance of prostate-specific antigen(PSA),phi,and the risk calculators in an additional observational cohort of 1045 men.We observed that the phi-based risk calculators(risk calculators 2 and 4)outperformed the PSA-based risk calculator for predicting PCa and high-grade PCa in the training cohort.In the validation study,the area under the receiver operating characteristic curve(AUC)for risk calculators 2 and 4 reached 0.91 and 0.92,respectively,for predicting PCa and high-grade PCa,respectively;the AUC values were better than those for risk calculator 1(PSA-based model with an AUC of 0.81 and 0.82,respectively)(all P<0.001).Such superiority was also observed in the stratified population with PSA ranging from 2.0 ng ml^-1 to 10.0 ng ml^-1.Decision curves confirmed that a considerable proportion of unnecessary biopsies could be avoided while applying phi-based risk calculators.In this study,we showed that,compared to risk calculators without phi,phi-based risk calculators exhibited superior discrimination and calibration for PCa in the Chinese biopsy population.Applying these risk calculators also considerably reduced the number of unnecessary biopsies for PCa.