Outcomes of locally advanced prostate cancer： a single institution study of 209 patients in Japan

Aim:To investigate the outcomes for Asian populations with locally advanced/clinical stage Ⅲ prostate cancer(PCa)treated with currently prevailing modalities.Methods:We reviewed the record of 209 patients with clinical stage ⅢPCa,who were treated at Niigata Cancer Center Hospital between 1992 and 2003.Treatment options included hor-mone therapy-combined radical prostatectomy(RP HT),hormone therapy-combined external beam irradiation(EBRT HT)and primary hormone therapy(PHT).Results:The 5-and 10-year overall survival rates were 80.3%and 46.1% in all cohorts,respectively.The survival rates were 87.3% and 66.5% in the RP HT group,94.9% and70.0% in the EBRT HT group and 66.1% and 17.2% in the PHT group,respectively.A significant survival advantagewas found in the EBRT HT group compared with that in the PHT group(P<0.0001).Also,the RP HT group hadbetter survival than the PHT group(P=0.0107).The 5-and 10-year disease-specific survival rates for all cases were92.5% and 80.0%,respectively.They were 93.8% and 71.4% in the RP HT group,96.6% and 93.6% in theEBRT HT group and 88.6% and 62.3% in the PHT group,respectively.A survival advantage was found in theEBRT HT group compared with the PHT group(P=0.029).No significant difference was found in disease-specificsurvival between the EBRT HT and RP HT groups or between the RP HT and PHT groups.Conclusion:Althoughour findings indicate that radiotherapy plus HT has a survival advantage in this stage of PCa,we recommend therapiesthat take into account the patients'social and medical conditions for Asian men with clinical stage Ⅲ PCa.(Asian JAndrol 2006 Sep;8:555-561)     

Should prostate cancer status be determined in patients undergoing radical cystoprostatectomy?

INTRODUCTION: We estimate the frequency of prostate cancers detected incidentally in radical cystoprostatectomy specimens and discuss whether the prostate cancer status should be determined in patients undergoing radical cystoprostatectomy. MATERIALS AND METHODS: A total of 97 radical cystoprostatectomies without evidence of prostate cancer on digital rectal examination were performed for transitional cell carcinomas of the bladder between January 2001 and May 2004. The mean patient age at the time of surgery was 66.9 +/- 9.52 (range 49-75) years. RESULTS: The overall incidence of prostate cancer detected in radical cystoprostatectomy specimens was 21.6% (21/97 specimens). The mean tumor volume was found to be 0.93 +/- 0.81 ml. The tumor volume was >0.5 ml in 12 cases (57.1%). The surgical margin was negative in all cases, and the disease was organ confined in 20 patients (95.2%). Capsular invasion was evident in 2 patients (9.5%), 1 of whom had lymph-node-positive disease. CONCLUSIONS: Despite the high prevalence of incidental prostate carcinomas among patients with bladder cancer undergoing cystoprostatectomy, the vast majority of the cancers are organ confined. However, the prostate cancer status should be determined on the basis of digital rectal examination and prostate-specific antigen in patients undergoing radical cystoprostatectomy - especially if prostate-sparing cystectomy is planned.     

Diagnostic strategies and the incidence of prostate cancer： reasons for the low reported incidence of prostate cancer in China

We have analysed the reasons for the low reported incidence of prostate cancer in China and argue for early diagnosis and treatment of this disease. According to the 2002 database of the International Agency for Research on Cancer （IARC）, the age-standardized incidence of prostate cancer in China is 1.6/105 person years （PY）, with a mortality rate of 1.0/105 PY and mortality-to-incidence rate ratio （MR/IR） = 0.63. The MR/IR ratio of prostate cancer in China was found to be higher than the average in Asia （MR/IR = 0.57） and much higher than that in North America （MR/IR = 0.13）. These data indicate that in China most prostate cancers were in the advanced stages at the time of diagnosis, and that patients had a short survival time thereafter. In 2004, Stamey et al. reported a retrospective American study of prostate cancer for the years 1983-2003. It was shown that most cases of prostate cancer detected by prostate-specific antigen （PSA） screening were in the advanced stage at the start of this 20-year period. These early follow-up data are quite similar to the results obtained from mass PSA screening of elderly men in Changchun, China. However, after the American programmes for early diagnosis and treatment of prostate cancer were accepted, tumours were diagnosed at earlier stages. On the basis of these findings, mass screening should be performed in the whole of China using serum PSA to facilitate early diagnosis and treatment of prostate cancer.     

Utility of tissue microarrays for profiling prognostic biomarkers in clinically localized prostate cancer： the expression of BCL-2, E-cadherin, Ki-67 and p53 as predictors of biochemical failure after radical prostatectomy with nested control for clinical and pathological risk factors

A cure cannot be assured for all men with clinically localized prostate cancer undergoing radical treatment. Molecular markers would be invaluable if they could improve the prediction of occult metastatic disease. This study was carried out to investigate the expression of BCL-2, Ki-67, p53 and E-cadherin in radical prostatectomy specimens. We sought to assess their ability to predict early biochemical relapse in a specific therapeutic setting. Eighty-two patients comprising 41 case pairs were matched for pathological stage, Gleason grade and preoperative prostate-specific antigen （PSA） concentration. One patient in each pair had biochemical recurrence （defined as PSA ≥ 0.2 ng mL^-1 within 2 years of surgery） and the other remained biochemically free of disease （defined as undetectable PSA at least 3 years after surgery）. Immunohistochemical analysis was performed to assess marker expression on four replicate tissue microarrays constructed with benign and malignant tissue from each radical prostatectomy specimen. Ki-67, p53 and BCL-2, but not E-cadherin, were significantly upregulated in prostate adenocarcinoma compared with benign prostate tissue （P 〈 0.01）. However, no significant differences in expression of any of the markers were observed when comparing patients who developed early biochemical relapse with patients who had no biochemical recurrence. This study showed that expression of p53, BCL-2 and Ki-67 was upregulated in clinically localized prostate cancer compared with benign prostate tissue, with no alteration in E-cadherin expression. Biomarker upregulation had no prognostic value for biochemical recurrence after radical prostatectomy, even after considering pathological stage, whole tumour Gleason grade and preoperative serum PSA level.     

Does diabetes mellitus increase the risk of high-grade prostate cancer in patients undergoing radical prostatectomy?

The objective was to test the hypothesis that in patients with prostate cancer undergoing radical prostatectomy (RP), diabetic patients are at a higher risk of harboring a high-grade tumor than non-diabetic patients. We examined 2060 consecutive men who underwent RP between 2001 and 2009. Of them, 7.1% had type 2 diabetes mellitus (DM). A high-grade tumor was defined as having a Gleason score ≥ 8. Univariable and multivariable logistic regression analyses were used to test the relationship between type 2 DM and high-grade tumor. Mean patient age was 64 years (range: 45-85). Mean total PSA level was 9 ng ml(-1) (range: 1-89.5). A significantly higher percentage of diabetic patients had high-grade tumor on biopsy (16.3 vs 7.6%; P = 0.001) and on RP specimen (21.1 vs 11.7%; P = 0.001) in comparison with non-diabetic patients. In multivariable analyses, DM was an independent predictor of high-grade tumor on biopsy (odds ratio = 2.31, P = 0.001) and on final pathological specimen (odds ratio = 2.22, P = 0.002). In patients undergoing RP, those with type 2 DM had a higher risk of harboring a poorly differentiated tumor on final pathological examination.     

Targeted-cryosurgical ablation of the prostate with androgen deprivation therapy： quality of life in high-risk prostate cancer patients

Aim:To present preliminary results on health-related quality of life(QoL),prostate-associated symptoms and thera-peutic effects of targeted-cryosurgical ablation of the prostate(TCSAP)with androgen deprivation therapy(ADT)inhigh-risk prostate cancer(PCa)patients.Methods:Thirty-four men with high-risk PCa features underwent TCSAP,and ADT was added to improve the treatment outcomes.High-risk parameters were defined as either prostate-specific antigen(PSA)≥10ng/mL,or Gleason score≥8,or both.The Genito-Urinary Group of the European Orga-nization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30(EORTC QLQ-C30)withprostate-cancer-specific module(QLQ-PR25)was used for evaluating morbidities and PSA levels were recordedevery 3 months.PSA failure was defined as the inability to reach a nadir of 0.4 ng/mL or less.Results:Although itwas not statistically significant,the global health status scores increased after TCSAP with ADT.The scores for fivefunctional scales also became higher after treatment.The most prominent symptom after treatment was sexualdysfunction,followed by treatment-related and irritative voiding symptoms.Conclusion:TCSAP with ADT appearsto be minimally invasive with high QoL except for sexual dysfunction.Long-term follow-up of PSA data and survivalis necessary before any conclusions can be made on the efficacy of this promising new therapeutic modality in thetreatment of PCa.(Asian J Androl 2006 Sep;8:629-636)     

Mass screening of prostate cancer in a Chinese population：the relationship between pathological features of prostate cancer and serum prostate specific antigen

Aim: To investigate the pathological features of the prostate biopsy through mass screening for prostate cancer in a Chinese cohort and their association with serum prostate specific antigen (PSA). Methods: A total of 12027 Chinese men in Changchun were screened for prostate cancer by means of the serum total prostate specific antigen tPSA test (by Elisa assay). Transrectal ultrasound-guided systematic six-sextant biopsies were performed on those whose serum tPSA value was > 4.0 ng/mL and those who had obstructive symptoms (despite their tPSA value) and were subject to subsequent pathological analysis with the aid of the statistic software SPSS 10.0 (SPSS. Inc., Chicago. USA). Results: Of the 12027 cases, 158 (including 137 patients whose serum tPSA values were 4.0 ng/mL and 21 patients [serum tPSA < 4.0 ng/mL] who had obstructive symptoms) undertook prostate biopsy. Of the 158 biopsies, 41 cases of prostatic carcinoma were found (25.9 %, 41/158). The moderately differentiated carcinoma and poorly differentiated carcinoma accounted for 61% and 34%, respectively. A significant linear positive correlation between the serum tPSA and the Gleason scores in the 41 cases of prostatic carcinoma (r = 0.312, P < 0.01) was established. A significant linear positive correlation between the serum tPSA value of the 41 prostatic carcinoma and the positive counts of carcinoma in sextant biopsies was established (r = 0.406, P < 0.01), indicating a significant linear relationship between serum tPSA and the size of tumor. Conclusion: This study was the first to conduct mass screening for prostate cancer by testing for serum tPSA values and the first to investigate the pathological features of prostate cancer in a cohort of Chinese men. Our results reveal that the moderately differentiated carcinoma is the most common type of prostate cancer. This study also has shown that the serum tPSA value in prostate cancer is associated with the Gleason score and the size of tumor.     

Does tadalafil prevent erectile dysfunction in patients undergoing radiation therapy for prostate cancer？

Arecently published paper addressed the interesting topic of prevention of erectile dysfunction （ED） with tadalafil, a pbosphodiesterase-type 5 inhibitor （PDE5i） in patients undergoing radiation therapy for localized prostate cancer. Tadalafil 5 mg or placebo was administered once-daily for 24 weeks in patients undergoing external-beam radiotherapy （EBRT） or brachytherapy （BT） for prostate cancer. This randomized trial did not show superior efficacy of the active drug compared with placebo 4-6 weeks after stopping the study drug. Furthermore, patients younger than 65 years did not respond significantlybetter than older patients.     

Exploring the role of anti-angiogenic therapies in prostate cancer： results from the phase 3 trial of sunitinib

Prostate cancer is aleading cause of cancer death in men. Despite recent advancesin our understanding and treatment of advanced disease, no systemic therapy is curative and new therapies are needed. Targeting angiogenesis is an attractive therapeutic strategy, as angiogenic pathways are upregulated in prostate tumors similar to other malignancies due to imbalance of pro- and anti-angiogenic factors secreted by tumor,     

Do androgen-directed therapies improve outcomes in prostate cancer patients undergoing radical prostatectomy? A systematic review and meta-analysis

IntroductionApproximately 50% of patients with non-metastatic prostate cancer are treated with radical prostatectomy (RP). While some men will be cured with surgery alone, a substantial proportion will experience cancer recurrence. Androgen-directed therapy (ADT) is an effective adjuvant therapy for patients treated with prostate radiation. Comparatively, the efficacy of ADT in surgical patients has not been well-studied.MethodsA systematic search of MEDLINE, Embase, and the Cochrane Library from inception to July 2020 was performed. Randomized trials comparing ADT with RP vs. prostatectomy alone in patients with clinically localized prostate cancer were included. Neoadjuvant ADT and adjuvant ADT interventions were assessed separately. The primary outcomes were cancer recurrence-free survival (RFS) and overall survival (OS). Pathological outcomes following neoadjuvant ADT were also evaluated.ResultsFifteen randomized trials met eligibility criteria; 11 evaluated neoadjuvant ADT (n=2322) and four evaluated adjuvant ADT (n=5205). Neoadjuvant ADT (three months of treatment) did not improve RFS (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.74–1.11) or OS (HR 1.22, 95% CI 0.62–2.41). Neoadjuvant ADT significantly decreased the risk of positive surgical margins (relative risk [RR] 0.48, 95% CI 0.41–0.56) and extraprostatic tumor extension (RR 0.75, 95% CI 0.64–0.89). Adjuvant ADT improved RFS (HR 0.65, 95% CI 0.45–0.93) but did not improve OS (HR 1.02, 95% CI 0.84–1.24).ConclusionsNeoadjuvant ADT causes a pathological downstaging of prostate tumors but has not been found to delay cancer recurrence nor extend survival. Few studies have evaluated adjuvant ADT. Trials are needed to determine the benefits and harms of intermediate- or long-term adjuvant ADT for RP patients.     

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.     

Expression and significance of estrogen receptor α and β in prostate cancer and peri-cancer tissue

Objective To investigate the expression of estrogen receptor (ER) α and β in human prostate cancer (PC), peri-cancer tissue and benign prostatic hyperplasia (BPH) tissue, and to discuss the role of estrogen receptor in prostate cancer. Methods The expression of ERα and ERβ in PC (n=28), peri-cancer tissue (n=28) and BPH (n=29) were detected by immunohistochemistry with En vision method. The ERα and ERβ expression were compared among different tissues by chisquare. The relationship between ER expression and related clinicopathologic features was statistically analyzed by spearman rank collection. Results ERα was localized dominantly in the stromal cell of PC. There were significant differences of the expression of ERα in PC, peri-cancer tissue and BPH tissue (epithelial cell 0%, 14%, 24%, P＜0. 05; stromal cell 57%, 68%, 31%,P＜0. 05). ERβ was localized in both epithelial and stromal cell of PC. There were significant differences of the expression of ERβ in PC, peri-cancer tissue and BPH tissue (epithelial cell 39%, 64%, 29%, P＜0.01; stromal cell 50%, 75%, 79%, P＜0.05). There was a significant difference of the expression of ERβ in different Gleason scores of PC tissue. Conclusions ERα is localized in the stromal cell of PC tissue.ERβ is localized in both epithelial and stromal cell of PC tissue. The ERβ might be related to the tumor differentiation of PC.     

Expression and significance of estrogen receptor α and β in prostate cancer and peri-cancer tissue

Objective To investigate the expression of estrogen receptor (ER) α and β in human prostate cancer (PC), peri-cancer tissue and benign prostatic hyperplasia (BPH) tissue, and to discuss the role of estrogen receptor in prostate cancer. Methods The expression of ERα and ERβ in PC (n=28), peri-cancer tissue (n=28) and BPH (n=29) were detected by immunohistochemistry with En vision method. The ERα and ERβ expression were compared among different tissues by chisquare. The relationship between ER expression and related clinicopathologic features was statistically analyzed by spearman rank collection. Results ERα was localized dominantly in the stromal cell of PC. There were significant differences of the expression of ERα in PC, peri-cancer tissue and BPH tissue (epithelial cell 0%, 14%, 24%, P＜0. 05; stromal cell 57%, 68%, 31%,P＜0. 05). ERβ was localized in both epithelial and stromal cell of PC. There were significant differences of the expression of ERβ in PC, peri-cancer tissue and BPH tissue (epithelial cell 39%, 64%, 29%, P＜0.01; stromal cell 50%, 75%, 79%, P＜0.05). There was a significant difference of the expression of ERβ in different Gleason scores of PC tissue. Conclusions ERα is localized in the stromal cell of PC tissue.ERβ is localized in both epithelial and stromal cell of PC tissue. The ERβ might be related to the tumor differentiation of PC.     

Androgen receptor expression in clinically localized prostate cancer： immunohistochemistry study and literature review

Aim： To evaluate androgen receptor （AR） expression in clinically localized prostate cancer （PCa）. Methods： Specimens were studied from 232 patients who underwent radical prostatectomy for clinically localized prostatic adenocarcinoma without neoadjuvant hormonal therapy or chemotherapy at our institution between November 2001 and June 2005. Immunohistochemical study was performed using an anti-human AR monoclonal antibody AR441. The mean AR density in the hot spots of different histological areas within the same sections were compared and the correlation of malignant epithelial AR density with clinicopathological parameters such as Gleason score, tumor, nodes and metastases （TNM） stage and pre-treatment prostate-specific antigen （PSA） value was assessed. Results： AR immunoreactivity was almost exclusively nuclear and was observed in tumor cells, non-neoplastic glandular epithelial cells and a proportion of peritumoral and interglandular stromal cells. Mean percentage of AR-positive epithelial cells was significantly higher in cancer tissues than that in normal prostate tissues （mean e SD, 90.0% ± 9.3% vs. 85.3% ±9.7%, P 〈 0.001）. The histological score yielded similar results. The percentage ofAR immunoreactive prostatic cancer nuclei and histological score were not correlated with existing parameters such as Gleason score, tumor, nodes and metastases stage and pre-treatment PSA value in this surgically treated cohort. Conclusion： The results of the present study suggest that there may be limited clinical use for determining AR expression （if evaluated in hot spots） in men with localized PCa.     

High expression of karyopherin-α2 defines poor prognosis in non-muscle-invasive bladder cancer and in patients with invasive bladder cancer undergoing radical cystectomy

Background

Conventional clinicopathologic risk factors have failed to accurately predict the prognosis of patients with bladder cancer (BC).

Objective

To evaluate karyopherin-α2 (KPNA2) expression as a progression marker in patients with non–muscle-invasive BC (NMIBC) treated by conservative methods and as a prognostic marker in patients with invasive BC undergoing radical cystectomy (RC).

Design, setting, and participants

Two different tissue microarrays were constructed, one with 234 primary Ta/T1 tumours from patients treated by transurethral resection of the bladder and one with 377 tumours from RC patients.

Intervention

KPNA2 expression based on immunohistochemistry.

Measurements

Risk of progression of Ta/T1 patients to muscle-invasive BC was estimated in clinical follow-up to progression or a minimum of 53 mo. Risk of recurrent disease and death following RC was estimated in clinical follow-up of a minimum of 24 mo in patients alive.

Results and limitations

A high KPNA2 expression in Ta/T1 patients was significantly correlated with a higher risk of progression that was independent of conventional risk factors in multivariate analysis. In patients undergoing RC, a high KPNA2 expression was an independent predictor of poor prognosis. A high KPNA2 expression was correlated with a higher risk of visceral metastasis rather than lymphatic spread.

Conclusions

KPNA2 expression is a marker for progression of NMIBC and a prognostic marker in patients undergoing RC.     

Prostate calculi in cancer and BPH in a cohort of Korean men：presence of calculi did not correlate with cancer risk

Prostatic calculi are common and are associated with inflammation of the prostate. Recently,it has been suggested that this inflammation may be associated with prostate carcinogenesis. The aim of this study was to investigate the relationship between prostatic calculi and prostate cancer （PCa） in prostate biopsy specimens. We retrospectively analyzed 417 consecutive patients who underwent transrectal ultrasonography （TRUS） and prostate biopsies between January 2005 and January 2008. Based on the biopsy findings,patients were divided into benign prostatic hyperplasia and PCa groups. TRUS was used to detect prostatic calculi and to measure prostate volume.The correlations between PCa risk and age,serum total PSA levels,prostate volume,and prostatic calculi were analyzed. Patient age and PSA,as well as the frequency of prostatic calculi in the biopsy specimens,differed significantly between both the groups （P〈0.05）. In the PCa group,the Gleason scores （GSs） were higher in patients with prostatic calculi than in patients without prostatic calculi （P = 0.023）. Using multivariate logistic regression analysis,we found that patient age,serum total PSA and prostate volume were risk factors for PCa （P = 0.001）,but that the presence of prostatic calculi was not associated with an increased risk of PCa （P = 0.13）. In conclusion,although the presence of prostatic calculi was not shown to be a risk factor for PCa,prostatic calculi were more common in patients with PCa and were associated with a higher GS among these men.     

Long-term survival of participants in the prostate ：ancer prevention trial

The Prostate Cancer Prevention Trial （PCPT） is a seminal study in the field of urology. More than 10years after its initial publication, updated data from this trial continue to shape our understanding of prostate cancer. Among the major findings from the PCPT has been the demonstration that prostate cancer is common in men with prostate-specific antigen （PSA） once thought to be in the normal range,~ finasteride prevents the development of benign prostatic hypertrophy,2 it increases the sensitivity of PSA3 and digital rectal examination.4 Furthermore the PCPT helped to establish the link between erectile dysfunction and cardiovascular disease,5 and perhaps most importantly finasteride demonstrated a 25% relative risk reduction in the diagnosis of prostate cancer compared with placebo.