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）

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.

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.

Factors influencing biochemical recurrence in patients who have received salvage radiotherapy after radical prostatectomy： a systematic review and meta-analysis

Several studies have evaluated the risk factors influencing biochemical recurrence （BCR） of prostate cancer in patients receiving salvage radiotherapy （SRT） for BCR after radical prostatectomy （RP）, but the results remain conflicting. In this study, we performed a meta-analysis to resolve this conflict. We searched the following databases： PubMed, Embase, and Web of Science using the following terms in ＂All fields＂： ＂salvage radiation therapy,＂ ＂salvage IMRT, S-IMRT, salvage radiotherapy, SRT, radical prostatectomy,＂ ＂RP, biochemical recurrence,＂ ＂BCR,＂ ＂biochemical relapse.＂ Eleven studies, with a total of 1383 patients, were included in our meta-analysis. Of all the variables, only Gleason score （GS） 〉7 （odds ratio [OR]： 3.82; 95% confidence interval [CI]： 2.60-5.64） and pathological tumor （pT） stage 〉3a （OR： 1.82; 95% Ch 1.36-2.42） were positively correlated with BCR. However, SRT combined with androgen deprivation therapy （ADT） （OR： 0.63; 95% CI： 0.44-0.90） and radiation therapy （RT） dose 〉64 Gy （OR： 0.35; 95% CI： 0.19-0.64） were negatively correlated with BCR. Perineural invasion （OR： 2.64; 95% CI： 1.11-6.26）, preoperative prostate-specific antigen （PSA） 〉10 ng m1-1 （OR： 1.36; 95% CI： 0.94-1.96）, positive surgical margin （OR： 0.92; 95% Ch 0.7-1.19）, and seminal vesicle involvement （SVI） （OR： 1.09; 95% Ch. 0.83-1.43） had no effect on BCR. Our meta-analysis indicated that pT stage, GS, RT dose, and SRT combined with ADT may influence BCR, while preoperative PSA, surgical margin, perineural invasion, and SVI have only a weak effect on BCR.

Clinical activity of abiraterone plus prednisone in docetaxel-naive and docetaxel-resistant Chinese patients with metastatic castration-resistant prostate cancer

This study investigated the clinical activity of abiraterone plus prednisone in docetaxel-naive and docetaxel-resistant Chinese patients with metastatic castratio n-resista nt prostate can cer(mCRPC).A total of 146 patie nts with docetaxel-naive group(103 cases)and docetaxel-resista nt group(43 cases)were en rolled from the Sha nghai Cancer Center(Sha nghai,Chin a)in this retrospective cohort study.The efficacy endpoints were prostate-specific antigen response rate,prostate-specific antigen progress!on-free survival,clinical/radiographic progression-free survival,and overall survival in response to abiraterone plus prednisone.Significantly higher prostate-specific antigen response rate was found in docetaxel-naive group(54.4%,56/103)compared to docetaxel-resistant group(34.9%,15/43)(P=0.047).In addition,significantly higher median prostate-specific antigen progress!on-free survival(14.0 vs 7.7 months,P=0.005),clinical or radiographic progression-free survival(17.0 vs 12.5 months,P=0.003),and overall survival(27.0 vs 18.0 mon ths,P=0.016)were found in docetaxel-naTve group compared to docetaxel-resistant group,respectively.The univariate and multivariate analyses indicated that lower albumin and visceral metastases were independent significant predictors for shorter overall survival.To sum up,our data suggested that abiraterone plus prednisone was efficient in both docetaxel-naTve and docetaxel-resistant Chinese patients.Moreover,higher PSA response rate and longer overall survival were observed in the docetaxel-naTve group,which suggested that abiraterone was more effective for docetaxel-naive patients than for docetaxel failures.

High IL-23^(+)cells infiltration correlates with worse clinical outcomes and abiraterone effectiveness in patients with prostate cancer

Individualized treatment of prostate cancer depends on an accurate stratification of patients who are sensitive to various treatments.Interleukin-23(IL-23)was reported to play a significant role in prostate cancer.Here,we aimed to explore the clinical value of IL-23-secreting(IL-23^(+))cells in prostate cancer patients.We evaluated interleukin-23A(IL-23A)expression in The Cancer Genome Atlas database and retrospectively enrolled 179 treatment-naive metastatic prostate cancer patients diagnosed in our institute between June 2012 and December 2014.IL-23^(+)cells were stained and evaluated via immunohistochemistry.Further,survival and multivariate Cox regression analyses were conducted to explore the prognostic value of IL-23^(+)cells.We found that IL-23A expression correlated with disease progression,while IL-23^(+)cells were clearly stained within prostate cancer tissue.Patients with higher Gleason scores and multiple metastatic lesions tended to have more IL-23^(+)cell infiltration.Further analyses showed that patients with higher levels of IL-23^(+)cells had significantly worse overall survival(hazard ratio[HR]=2.996,95%confidence interval[95%CI]:1.812–4.955;P=0.001)and a higher risk of developing castration resistance(HR=2.725,95%CI:1.865–3.981;P=0.001).Moreover,subgroup analyses showed that when patients progressed to a castration-resistant status,the prognostic value of IL-23^(+)cells was observed only in patients treated with abiraterone instead of docetaxel.Therefore,we showed that high IL-23^(+)cell infiltration is an independent prognosticator in patients with metastatic prostate cancer.IL-23^(+)cell infiltration may correlate with abiraterone effectiveness in castration-resistant prostate cancer patients.

Prognostic value of PTEN in de novo diagnosed metastatic prostate cancer

The purpose of our study is to investigate the prognostic value of phosphatase and tensin homolog on chromosome 10(PTEN)expression in patients with de novo metastatic castration naive prostate cancer(mCNPC).A total of 205 patients with mCNPC at Fudan University Shanghai Cancer Center(Shanghai,China)were retrospectively examined.Immunohistochemical staining of PTEN was performed on prostate biopsy samples of these patients.Associations among clinicopathological features,patient survival and PTEN protein expression were analyzed.PTEN loss occurred in 58 of 205(28.3%)patients.Loss of PTEN was significantly correlated with high metastatic volume(P=0.017).No association between PTEN expression and Gleason score was observed.Patients with PTEN loss had significantly shorter progression-free survival(PFS,P<0.001)and overall survival(OS,P<0.001)compared with patients with intact PTEN expression.Multivariate analysis showed that elevated alkaline phosphatase,high metastatic volume and PTEN loss were independent poor prognostic factors for PFS.The Eastern Cooperative Oncology Group performance status(ECOG PS)≥2 and PTEN loss were independent poor prognostic factors for OS.The adjusted hazard ratio of PTEN loss for PFS and OS was 1.67(95%confidence interval[CI]:1.14–2.43,P=0.008)and 1.95(95%CI:1.23–3.10,P=0.005),respectively.PTEN loss was also significantly associated with shorter PFS(P=0.025)and OS(P<0.001)in patients with low-volume metastatic disease.Our data showed that PTEN loss is an independent predictor for shorter PFS and OS in patients with de novo mCNPC.