Prostate-specific Antigen Failure-free Survival Research Articles

Long-term outcomes of three-dimensional conformal radiation therapy combined with neoadjuvant hormonal therapy for Japanese patients with T1c-T2N0M0 prostate cancer

The outcomes of three-dimensional conformal radiation therapy (3D-CRT) combined with neoadjuvant hormonal therapy (NAHT) in Japanese patients with T1c-T2N0M0 prostate cancer, with initiation of salvage hormonal therapy (SHT) at a relatively early phase, were analyzed. Fifty-nine Japanese patients with T1c-T2N0M0 prostate cancer who received radical 3D-CRT between January 1999 and January 2003 were evaluated. The median age, initial prostate-specific antigen (PSA) level, and duration of NAHT were: 72 years, 9.4 ng/ml, and 6 months, respectively. Seventy Gy was given in 35 fractions confined to the prostate ± seminal vesicles. AHT was not administered after 3D-CRT in any patients. The median follow-up period was 89 months. The median PSA value at the time of initiation of SHT was 4.7 ng/ml (range 0.1-21.6 ng/ml). The overall, disease-specific, PSA failure-free (based on the Phoenix definition), and SHT-free survival rates at 8 years were 82.8% (95% confidence interval [CI] 72.4-93.2), 100%, 62.4% (47.1-77.8), and 82.6% (71.3-94.0), respectively. Only one patient developed grade 3 late toxicity. The PSA control rates in our series of Japanese patients with stage T1c-T2N0M0 prostate cancer treated with the standard dose of 3D-CRT combined with NAHT seemed at least comparable to those reported from Western countries; as well, the patients had excellent outcomes. The present outcomes can be used as basic data for evaluating the impact of dose escalation with intensity-modulated radiation therapy for Japanese patients with prostate cancer in the future.

Expression of CD147 is associated with prostate cancer progression

Novel molecular markers that are associated with prostate cancer (PCa) progression will provide valuable information in the diagnosis and treatment of the disease. Extracellular matrix metalloproteinase inducer (CD147) has been demonstrated to be involved in tumor invasion, metastasis, growth and survival. In our study, we examined whether the expression of CD147 can be used as a prognostic marker for predicting PCa progression. Tissue samples from 240 patients who received radical prostatectomy for PCa were obtained. CD147 expression in these samples was evaluated using immunohistochemical staining with a monoclonal antibody specifically against CD147. Increased expression of CD147 was correlated with higher Gleason scores (GS), positive surgical margin, prostate-specific antigen (PSA) failure, metastasis and reduced overall survival. Both univariate Cox regression analysis and multivariate analysis including competing biological variables demonstrated that increased CD147 expression was associated with increased risk for reduced PSA failure-free, metastasis-free and overall survival. Kaplan-Meier survival curves showed that the CD147 overexpression was a significant predictor for the PSA failure-free, metastasis-free and the overall survival in both pT2 and pT3 PCa patients. More significantly, higher expression of CD147 can serve as an independent prognostic predictor for PSA failure-free survival in PCa patients when they are stratified by GS. Our study results demonstrate the involvement of CD147 in PCa progression and suggest its potential role as an independent predictor of biochemical recurrence, development of metastasis and reduced overall survival in PCa.

Which Patients With Undetectable PSA Levels 5 Years After Radical Prostatectomy Are Still at Risk of Recurrence?—Implications for a Risk-adapted Follow-up Strategy

To determine the predictors of late prostate-specific antigen (PSA) failure among men with an undetectable PSA level 5 years after radical prostatectomy (RP). A total of 505 men who had undergone RP for prostate cancer from 1985 to 2000 at Brigham and Women's Hospital and who had ≥ 5 years of recurrence-free survival (ie, all PSA levels < 0.2 ng/mL) constituted the study cohort. Cox multivariate regression analysis was used to determine the factors associated with PSA failure after 5 years. Kaplan-Meier analysis was used to estimate the PSA failure-free survival rate. The median follow-up was 10.7 years after RP (interquartile range 7.8-13.3). No patient had PSA failure at year 5, but the PSA failure-free survival rate for this cohort at year 10 was 88% (95% confidence interval 84.4%-91.0%) and, at year 13, was 82% (95% confidence interval 77.0%-86.0%). On multivariable regression analysis, the factors associated with failure after year 5 were Gleason score 7 (adjusted hazard ratio [AHR] 1.88, P = .036), Gleason score 8-10 (AHR 4.81, P ≤ .002), extracapsular extension (AHR 2.37, P = .003), and seminal vesicle invasion (AHR 1.52, P = .062). Among men with an undetectable PSA level 5 years after RP, Gleason score 7, Gleason score 8-10, extracapsular extension, and seminal vesicle invasion were significant predictors of subsequent late PSA failure. Patients with these factors (particularly Gleason score 8-10 or seminal vesicle invasion) should have continued close monitoring of their PSA level and consideration of early salvage, as appropriate. However, patients with Gleason score 6 disease were very unlikely to develop late recurrence and might be candidates for less-intense follow-up once they have passed the 5-year mark.

Prognostic significance of global grading system of Gleason score in patients with prostate cancer with bone metastasis

To investigate the influence of the revised Gleason grading system (GGS, revised at a consensus conference organized by the International Society of Urological Pathology in 2005) on prediction of prognosis for patients with prostate cancer with bone metastasis. Prostatic needle biopsy specimens from 113 patients with prostate cancer with bone metastasis were scored using the conventional GGS (CGGS), modified global GGS (MGGGS), and modified highest GGS (MHGGS). The patients were divided into two groups (Gleason score < or = 7 and > or = 8) using each grading system. Prostate-specific antigen failure-free survival after hormone therapy (HT) was estimated retrospectively. The Cox proportional hazard method was used for univariate and multivariate analysis. Patients with a Gleason score of < or = 7 had a significantly longer remission than patients with a score of > or = 8 according to each GGS. However, the better prognosis patients were detected more precisely by the CGGS and MGGGS than the MHGGS. Multivariate analysis showed that the CGGS and MGGGS were significant prognostic indicators for the outcome of HT after adjustment for other prognostic factors. These results suggest that the CGGS and MGGGS are more useful than the MHGGS as prognostic indicators for HT. Further evaluation in larger series is needed to define its clinical usefulness.

1559 PROSTATE CANCER ARISING IN THE TRANSITION ZONE: CHARACTERIZATION OF THE INCIDENCE, ANATOMICAL EXTENSION PATTERN AND PROGNOSTIC FACTORS

You have accessJournal of UrologyProstate Cancer: Localized VI1 Apr 20101559 PROSTATE CANCER ARISING IN THE TRANSITION ZONE: CHARACTERIZATION OF THE INCIDENCE, ANATOMICAL EXTENSION PATTERN AND PROGNOSTIC FACTORS Go Kimura, Ichiro Matsuzawa, Yuka Saito, Yasutomo Suzuki, Tsutomu Hamasaki, and Yukihiro Kondo Go KimuraGo Kimura More articles by this author , Ichiro MatsuzawaIchiro Matsuzawa More articles by this author , Yuka SaitoYuka Saito More articles by this author , Yasutomo SuzukiYasutomo Suzuki More articles by this author , Tsutomu HamasakiTsutomu Hamasaki More articles by this author , and Yukihiro KondoYukihiro Kondo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1324AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The transition zone cancer (TZC) has been reported to comprise 24% of prostate cancer (McNeal JE et al., Am J Surg Pathol, 1988) and the progosis is controversial. The aim of this study is to characrerize the incidence, anatomical extension pattern and prognostic factors of TZC in the era of PSA and extended biopsy. METHODS From 2000 to 2007, radical prostatectomy with no neoadjuvant therapy was performed in 358 cases in our hospital. Serial whole mount sections were reviewed to determine the incidense of TZC. The TZ was devided into four sub-zones, T1 (anteromedian), T2 (anterolateral), T3 (posterolateral) and T4 (posteromedian) (Fig 1). The sub-zonal incidence of the tumor in the TZ was also determined. The correlation between cancer occupation of each TZ subzone and clinicopathological factors including PSA and bladder neck invasion (b+) was studied by the Spearman's rank correlation. PSA failure-free survival was compared between TZC and non-TZC in all cases and subgroups inclluding the group A (PSA≤10), group B (10-20) and group C (>20) by Kaplan-Meier analysis using the logrank test. Cox proportional hazards models were used to assess prognostic factors. RESULTS The zonal origin of prostate cancer was 2% in the CZ, 68% in the PZ and 30% in the TZ. The sub-zonal tumor incidence devided by all cases was 53% in T1, 51% in T2, 29% in T3, and 23% in T4. Both PSA and b+ were significantly correlated with each of sub-zonal tumor occupation (Spearman's rho: T4>T3>T2>T1). A 5-year PSA failure-free surviaval of TZC was significantly better than that of non-TZC in the group B (91% vs. 49%) and the group C (78% vs. 40%). In PSA>20 cases positive surgical margin (PSM: HR=25.361) and TZC (HR=0.152) were the independent prognostic factors. In TZC cases only PSM was the independent prognostic factor (HR=19.608). CONCLUSIONS The TZC accounted for 30% of all prostate cancer in our RP cases. The TZC tends to arise from anterior portion of the TZ and extend toward both lower portion of the TZ and bladder neck along the urethra during progression. Since even in the cases with high PSA values TZC showed good prognosis in case of negtive surgical margin, a wide excision of bladder neck is recommended in high PSA value cases. Tokyo, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e602 Peer Review Report Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Go Kimura More articles by this author Ichiro Matsuzawa More articles by this author Yuka Saito More articles by this author Yasutomo Suzuki More articles by this author Tsutomu Hamasaki More articles by this author Yukihiro Kondo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

229 HOW DOES ETS FAMILY CONTRIBUTE TO PROSTATE CANCER PROGRESSION?

You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2010229 HOW DOES ETS FAMILY CONTRIBUTE TO PROSTATE CANCER PROGRESSION? Takeo Kosaka, Akira Miyajima, Shuji Mikami, Eiji Kikuchi, Suguru Shirotake, Takahiro Maeda, and Mototsugu Oya Takeo KosakaTakeo Kosaka More articles by this author , Akira MiyajimaAkira Miyajima More articles by this author , Shuji MikamiShuji Mikami More articles by this author , Eiji KikuchiEiji Kikuchi More articles by this author , Suguru ShirotakeSuguru Shirotake More articles by this author , Takahiro MaedaTakahiro Maeda More articles by this author , and Mototsugu OyaMototsugu Oya More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.287AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recurrent gene fusions between TMPRSS2 and the ETS transcription factors have been identified in prostate cancer (PCa) development. However, the function of fusion products has not been well characterized. We previously showed long-term androgen ablation induced Ets-1 up-regulation in prostate cancer (Kosaka T, Prostate 2009). In this study, we examined the expression and the function of Ets-1, and determined its prognostic significance and correlation with hormone-independency. METHODS Total 139 human PCa specimens: 119 specimens (group AD) from patients who underwent radical prostatectomy for localized PCa and 20 specimens (group HR) from patients who died of hormone-refractory prostate cancer (HRPC) were enrolled in this study. Immunohistochemistry (IHC) was used to investigate Ets-1 and CD34:MVD. The median follow up was 70.5 months. Progression free survival was calculated by the Kaplan-Meier method. Multivariate analysis was performed using Cox regression model. Three human PCa cell lines LNCaP, C4-2, and C4-2AT6 (Established at our laboratory under androgen-ablated condition medium, Prostate 2009) were analyzed in vitro and in vivo. Ets-1 expression was transiently down-regulated using siRNA directed against Ets-1 (si-Ets-1). RESULTS The expression of Ets-1 in the nucleus and MVD in group HR were significantly higher than group AD (p<0.001). There was s significant positive correlation between Ets-1 and MVD (Spearman′s correlation, r=0.752, p<0.001). There were statistically significant correlation between Ets-1 expression and MVD (p<0.001), and extracapsular extension of cancer (ECE) (p<0.001). During a median 70.5 months follow-up period, PSA failure was confirmed in 30 patients. There were significant differences in PSA failure-free survival (log-rank test, p<0.001), ECE (p<0.001) with regard to Ets-1 expression, MVD, ECE, and LVI. The 5-year PSA failure-free survival was 43.0% for patients with higher Ets-1 expression compared to 88.8% for patients with lower Ets-1 expression. Multivariate Cox regression analysis indicated that higher Snail expression (p=0.002) and LVI (p=0.008) were independent prognostic factors. C4-2AT6 expressed Ets-1 in the nucleus more strongly than C4-2 and LNCaP cells in vitro and in vivo, accompanied by higher VEGF production. Knockdown of Ets-1 by si-Ets-1 resulted in a matched reduction in VEGF production in C4-2AT6 and C4-2. CONCLUSIONS These results indicated that increased expression of Ets-1 in the nucleus, which found to be prognostic indicator, were associated with angiogenesis and hormone-independency. Tokyo, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e89-e90 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takeo Kosaka More articles by this author Akira Miyajima More articles by this author Shuji Mikami More articles by this author Eiji Kikuchi More articles by this author Suguru Shirotake More articles by this author Takahiro Maeda More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

296 EJACULATORY DUCT INVASION OF PROSTATE CANCER: A NEW PATHOLOGICAL PROGNOSTIC FACTOR

You have accessJournal of UrologyProstate Cancer: Localized I1 Apr 2010296 EJACULATORY DUCT INVASION OF PROSTATE CANCER: A NEW PATHOLOGICAL PROGNOSTIC FACTOR Go Kimura, Ichiro Matsuzawa, Yuka Saito, Yasutomo Suzuki, Tsutomu Hamasaki, and Yukihiro Kondo Go KimuraGo Kimura More articles by this author , Ichiro MatsuzawaIchiro Matsuzawa More articles by this author , Yuka SaitoYuka Saito More articles by this author , Yasutomo SuzukiYasutomo Suzuki More articles by this author , Tsutomu HamasakiTsutomu Hamasaki More articles by this author , and Yukihiro KondoYukihiro Kondo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.358AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The aim of this study is to characrerize the incidence, clinicopathological features and prognostic significance of ejaculatory duct invasion of prostate cancer. METHODS From 2000 to 2007, radical prostatectomy with no neoadjuvant therapy was performed in 358 cases in our hospital. Serial whole mount sections were reviewed to determine the incidence of ejaculatory duct invasion (ED+) including M6+ (ED+ of midgland) and B3+ (ED+ of base). The differences of clinicopathological factors including PSA, ope Gleason score (oGS), pathological organ confined disease (pOCD), capsular penetration (cap+), seminal vesicle invasion (sv+), positive surgical margin (ew+) and lymph node metastasis (pN1) between ED+ and ED-, M6 only+ and the others, and B3 and B3- were studied by the Mann-Whitney test. PSA failure-free survival was compared between ED+ and ED-, M6 only+ and the others, and B3+ and B3- by Kaplan-Meier analysis using the logrank test. RESULTS The ED+, M6 only+, both M6+ and B3+, and B3 only+ were observed in 79 (22%), 47 (13%), 21 (6%) and 11 cases (3%). As shown in Table 1, ED+ showed significantly worse clinicopathological factors including PSA, oGS, pOCD, ew+, cap+, sv+ and pN1 than ED-. This trend was emphasized in B3+ vs. B3-. Even in the cases of PSA≤10, this trend was not disappeared except for pN1 (Table 2). A 5-year PSA failure-free surviaval of ED+ vs. ED-, and B3+ vs. B3- was 67% vs. 83% (p=0.0146), and 48% vs. 82% (p=0.002), respectively. In the cases of PSA≤10, a 5-year PSA failure-free surviaval of ED+ vs. ED-, and B3+ vs. B3- was 73% vs. 92% (p=0.0118), and 62% vs. 91% (p=0.0002), respectively. CONCLUSIONS To our knowledge this study provides the first characterization of ED+. ED+ is relatively rare, but, associated with a high risk of adverse pathological and prognostic features. If ED+ can be determined preoperatively, aggressive intervention may be required. Tokyo, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e117-e118 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Go Kimura More articles by this author Ichiro Matsuzawa More articles by this author Yuka Saito More articles by this author Yasutomo Suzuki More articles by this author Tsutomu Hamasaki More articles by this author Yukihiro Kondo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Radical prostatectomy for high‐risk prostate cancer: Biochemical outcome

To determine the biochemical outcome following radical prostatectomy alone in patients with high-risk prostate cancer. Between January 2002 and August 2007, 252 patients underwent radical retropubic prostatectomy. Those who received neoadjuvant hormone therapy were excluded from this analysis. Based on pre-operative data, we stratified the patients into low, intermediate, and high-risk groups according to the risk criteria of the National Comprehensive Cancer Network in 2003, respectively. Prostate-specific antigen (PSA) failure was defined as any detectable PSA level higher than 0.2 ng/mL. The PSA failure-free survival rate for the high-risk group (n = 46) was 64.5% after a median follow-up period of 39 months. Among patients with high-risk disease, none with pathologically organ-confined cancer (n = 19) and a negative surgical margin had PSA failure. The PSA failure-free rate in patients with non organ-confined cancer (n = 27) was 39.5%. Among the pretreatment variables, a positive biopsy core percentage (the number of positive biopsy cores/total biopsy core) >or=30 was a significant independent predictor of extra prostatic extension. Radical prostatectomy is feasible in high-risk prostate cancer patients, only if they have a pathologically organ-confined disease.

Risk Stratification of High-grade Prostate Cancer Treated with Antegrade Radical Prostatectomy with Intended Wide Resection

The aim of this study was to assess the surgical outcome of high-grade prostate cancer (PCA) treated with antegrade radical prostatectomy with intended wide resection (aRP) and to establish the risk stratification. A consecutive 77 Japanese patients with Gleason score 8-10 PCA were treated with aRP alone and excluding patients with persistently elevated prostate-specific antigen (PSA), prospectively observed without any treatment until PSA failure was confirmed. PSA failure-free, cancer-specific and overall survival curves were generated with Kaplan-Meier method and the difference between groups was assessed with log-rank test. Cox's proportional hazards model was used to elucidate predictors of PSA failure. During a median follow-up of 6 years, PSA failure was observed in 41 (53%) of the 77 patients. Five- and 10-year PSA failure-free survival rates of the entire cohort were 44.6% and 40.1%, respectively. Both overall and cancer-specific survival rates of the entire cohort at 5 and 10 years were 96.8% and 87.9%, respectively. In a multivariate analysis, PSA (P = 0.008), specimen confinement (SC) (P = 0.006) and persistently elevated PSA after aRP were identified as significant and independent predictors of PSA failure. When stratifying patients into three risk groups according to PSA level and SC status, PSA failure-free survival rate in patients with PSA < 10 ng/ml and specimen-confined disease (SCD) was significantly better than that in those of any other groups. Good prognosis can be expected in patients with high-grade PCA treated with aRP alone when PSA < 10 ng/ml and the tumor was removed as an SCD.

Lymphovascular invasion is an independent predictor of prostate‐specific antigen failure after radical prostatectomy in patients with pT3aN0 prostate cancer

To investigate the association of lymphovascular invasion (LVI) in radical prostatectomy (RP) specimens with prostate-specific antigen (PSA) failure in patients with pT3aN0 prostate cancer (PCA). We retrospectively reviewed the clinical records of 94 patients with pT3aN0 PCA treated with RP alone. All of the 94 patients were prospectively observed without any treatment until PSA failure was confirmed. We investigated the association of LVI with the adverse pathological findings in RP specimens and the PSA failure-free survival rate. The Cox proportional hazard model was used to elucidate predictors of PSA failure. Median follow up was 47.4 months (quartile range 9.1 to 146.8). LVI was found in 26 (27.7%) of the 94 patients. In a multivariate analysis, PSA (P = 0.0054) and LVI (P = 0.015) were significant and independent predictors of PSA failure. Stratifying patients into four risk groups by LVI status and PSA level, the PSA failure-free survival rate in patients with negative LVI and PSA < or =10 ng/mL was significantly better than any other groups (positive LVI and/or PSA >10 ng/mL). Adjuvant therapy would not be indicated to patients with pT3aN0 PCA with negative LVI and PSA < or =10 ng/mL.

Prognostic Significance of Cancer Volume Involving Seminal Vesicles in Patients With pT3bpN0 Prostate Cancer

To investigate the prognostic effect of the prostate cancer (PCa) volume involving the seminal vesicles (CVSVs) in the radical prostatectomy specimen from patients with Stage pT3bpN0 PCa. We retrospectively reviewed the clinical records of 27 patients with Stage pT3bpN0 PCa who had undergone radical prostatectomy alone. We measured the CVSVs using a grid method on the glass slide under microscopic inspection and investigated the association of the CVSVs with clinicopathologic variables. Prostate-specific antigen (PSA) failure was confirmed in 11 of the 27 patients (41%) during a median follow-up of 34 months. The 3-year PSA failure-free survival rate was 48%. The median CVSVs was 1.14 cm(3). On univariate analysis, a CVSVs of >1.63 cm(3) was associated with positive surgical margins (P = .018), bilateral seminal vesicle involvement (P = .03), a long maximal tumor dimension (P = .031), and a greater preoperative PSA level (P = .0007). The 3-year PSA failure-free survival rate for those with a CVSVs of <or=1.63 cm(3) vs >1.63 cm(3) was 80% and 0%, respectively (P = .0009). On multivariate analysis, only the PSA level and CVSVs were identified as significant and independent predictors of PSA failure. Stratifying patients into 3 risk groups by these predictors, the PSA failure-free survival rate for patients with a PSA level >or=10 ng/mL and a CVSVs of >1.63 cm(3) was significantly worse than for any other group. The CVSVs is useful and invaluable as an independent predictor of PSA failure in patients with Stage pT3bpN0 PCa. The measurement of the CVSVs is simple and helped to determine the indication for adjuvant treatment after radical prostatectomy.

Salvage therapy with bicalutamide 80mg in patients with PSA failure under medical or surgical castration for prostate cancer

16010 Background: Previous American studies reported modest effects of deferred use of bicalutamide 150mg in patients with hormone refractory prostate cancer (HRPC) during androgen deprivation monotherapy (ADMT). The objective of the current study was to evaluate the potential benefit of sequential introduction of bicalutamide 80mg therapy in Japanese patients with rising PSA under definitive LHRH agonist therapy or surgical castration for prostate cancer. Methods: Forty-seven patients with HRPC during ADMT were treated with deferred combined androgen blockade (CAB) therapy, administering bicalutamide 80mg once-daily. HRPC was defined biochemically as three consecutive rises in PSA levels during ADMT. The treatment response was defined as a 50% or greater decline in PSA levels. Prognostic values of various pretreatment parameters for responsiveness to deferred CAB were statistically determined. When the disease relapsed during deferred CAB, bicalutamide was discontinued and the patients were evaluated for the antiandrogen withdrawal syndrome (AWS). Results: Of the 47 patients, 31 (66%) experienced a PSA response. The median PSA failure-free survival was 10 months. Biopsy Gleason score (GS) was the only pretreatment variable predictive of a PSA response (mean GS 7.9 in responders and 8.8 in non-responders, P=0.017). Biopsy GS (6 or 7 vs. 8–10: HR 1.51, P=0.028) and PSA-doubling time (PSA-DT less than 4 vs. 4 or more: HR 0.67, P=0.018) were the only statistically significant variables of PSA failure-free survival in multivariate analysis. None of the variables including serum PSA levels, response or duration of response of first line ADMT or presence or absence of metastatic lesions were not related to the response of deferred CAB or PSA failure-free survival. Responders to deferred CAB had statistically longer cancer-specific survival than non- responders. None of 22 patients who were evaluated for AWS had the condition. Conclusions: Deferred CAB using bicalutamide 80mg is effective second line therapy at least in Japanese patients with progression during ADMT, particularly in those with lower GS tumors or longer PSA-DT. AWS after deferred CAB is uncommon. No significant financial relationships to disclose.

A seven-year experience of HDR brachytherapy boost for localized prostate cancer: Biopsy and PSA outcome

Purpose: To evaluate PSA failure-free survival and 24-month prostate biopsy outcome in patients with localized prostate cancer treated with inverse-planned HDR brachytherapy boost.

Preoperative Serum Testosterone Level as an Independent Predictor of Treatment Failure following Radical Prostatectomy

ObjectivesPreoperative low serum testosterone (TS) level has been reported to be associated with adverse pathologic results in patients with clinically localized prostate cancer (pCA) treated with radical prostatectomy (RP). However, prior studies failed to show prognostic impact of preoperative low TS in these patients. The aim of this study was to investigate the relationship between preoperative TS and prostate-specific antigen (PSA) failure in these patients. MethodsOf 304 patients diagnosed with clinically localized pCA who had been treated with RP alone, 272 patients whose preoperative TS level had been measured were eligible for this analysis. Postoperative TS levels were also available in 222 of the 272 patients. Cox proportional hazard model was used to elucidate factors predictive for PSA failure. ResultsOf the 272 patients 49 had low (<300ng/dl) and 223 had normal preoperative TS level. In a stepwise multivariate analysis, preoperative TS (p=0.021) was an independent and significant predictor of PSA failure along with RP Gleason score (p=0.006), surgical margin status (p=0.0001), and PSA (p=0.0001). Five-year PSA failure–free survival rate of the patients with preoperative low TS (67.8%) was significantly worse than that with normal TS (84.9%) (p=0.035). Serum TS levels increased significantly after RP (p<0.0001). The increment of TS level in preoperative low TS group was significantly greater than that in preoperative normal TS group (p=0.0003). ConclusionsThe current results demonstrated that preoperative TS level is an independent and significant predictor of PSA failure after RP in patients with clinically localized pCA.

Results of radiation therapy combined with neoadjuvant hormonal therapy for stage III prostate cancer: comparison of two different definitions of PSA failure

We herein report the clinical outcome of radical radiation therapy combined with neoadjuvant hormonal therapy (NHT) for stage III (International Union Against Cancer [UICC] 1997: UICC 97) prostate cancer. Prostate-specific antigen (PSA) failure-free survival was assessed according to two different definitions, and the appropriateness of each definition is discussed. Between October 1997 and December 2000, 27 patients with stage III prostate cancer were enrolled in this study. The median pretreatment PSA level was 29 ng/ml (range, 7.4-430 ng/ml). The Gleason score (GS) was 7 or more in 22 patients (81%). All patients received 3 months of NHT with a luteinizing hormone-releasing hormone (LH-RH) analogue, in combination with an antiandrogen (flutamide), given during the first 2 weeks, followed by 70-Gy external-beam radiation therapy (EBRT) in 35 fractions. The initial 46 Gy was given with a four-field technique, while the remainder was given with a dynamic conformal technique. No adjuvant hormonal therapy (AHT) was given. The median follow-up time was 63 months. PSA levels decreased to the normal range (<4 ng/ml) after irradiation in all but one patient. The 5-year PSA failure-free survival was 34.8% according to the American Society for Therapeutic Radiology and Oncology (ASTRO) definition and it was 43.0% according to the "nadir plus 2" definition. Discordance of the results between the two definitions was seen in two patients. The 5-year overall and cause-specific survivals were 83.0% and 93.3%, respectively. No severe acute or late adverse effects were observed. Seventy Gy of EBRT following 3 months of NHT produced therapeutic results comparable to those reported in other studies which used long-term AHT. The value of long-term AHT for Japanese men should be tested in a clinical trial.

Deferred combined androgen blockade therapy using bicalutamide in patients with hormone‐refractory prostate cancer during androgen deprivation monotherapy

To assess the effect of adding bicalutamide on serum prostate-specific antigen (PSA) levels in patients with hormone-refractory prostate cancer (HRPC) during androgen deprivation monotherapy (ADMT). Forty-four patients with HRPC were treated with deferred combined androgen blockade (CAB) therapy, administering bicalutamide 80 mg once daily. HRPC was defined biochemically as three consecutive rises in PSA level during ADMT. The treatment response was defined as a > or = 50% decline in PSA levels. Prognostic values of various pretreatment variables for responsiveness to deferred CAB were determined statistically. When the disease relapsed during deferred CAB, bicalutamide was discontinued and the patients were evaluated for the antiandrogen withdrawal syndrome (AWS). Of the 44 patients, 29 (66%) had a PSA response; the median PSA failure-free survival was 9.2+ months. Biopsy Gleason score was the only pretreatment variable predictive of a PSA response (mean Gleason score 7.9 in responders and 8.7 in nonresponders). The PSA doubling time (PSA-DT) was the only statistically significant variable of PSA failure-free survival in a multivariate analysis. The 1- and 2-year PSA failure-free survival rates were 43% and 31% in patients with a PSA-DT of >4 months, while it was 21% and none, respectively, in those with a PSA-DT of <4 months. Responders to deferred CAB had a statistically longer cancer-specific survival than nonresponders. None of 20 patients who were evaluated for AWS had the condition. Deferred CAB therapy using bicalutamide is effective in patients with progression during ADMT, particularly in those with lower Gleason score tumours or a longer PSA-DT. AWS after deferred CAB is uncommon.

Prostate‐specific antigen failure within 2 years of radical prostatectomy predicts overall survival

This study attempts to determine whether prostate-specific antigen (PSA) failure following radical retropubic prostatectomy (RRP) affects patients' long-term overall survival. This study examined 155 men diagnosed as clinical stages T1b-T3a who received RRP as primary therapy. To evaluate whether PSA failure following RRP affects overall survival, the patients were grouped into those who experienced PSA failure within 2 years and those who did not. Clinical failure-free survival, prostate cancer-specific survival and overall survival were used as endpoints. Comparisons of survival curves were performed using the log-rank test. Logistic regression analysis was performed to determine the variable most predictive of PSA failure within 2 years of surgery. At 10 years, the PSA failure-free survival rate, clinical failure-free survival rate, prostate cancer specific survival rate and overall survival rate of the 155 patients were 40.1%, 83.1%, 94.9% and 84.2%, respectively. The overall survival curve for patients with PSA failure within 2 years of surgery was significantly lower than for patients with no PSA failure within 2 years of surgery (P = 0.042). The multivariate logistic regression analysis demonstrated that PSA greater than 20 ng/mL and poor differentiation of the tumor were significant independent predictors of PSA failure within 2 years of surgery. These results imply that prospective studies should be conducted to detect patients at high risk for PSA recurrence in whom metastasis may occur early and to investigate postoperative treatments for these high-risk patients to improve overall survival.

Radiation dose escalation combined with hormone therapy improves outcome in localised prostate cancer

We present the impact of systematic radiation dose escalation from 64 Gy to 66 Gy to 70 Gy on the outcome after radiation therapy (RT) alone or combined with hormonal treatment (HT) in a series of 494 consecutive localised prostate cancer patients treated during 1990–1999. Prognostic factors for prostate-specific antigen (PSA) failure, overall survival (OS) and prostate cancer specific survival (CSS) were investigated using multivariate analysis. T stage, pre-treatment PSA, grade, radiation dose and HT were found to be independent predictors of PSA failure. T stage, grade and HT were also independent predictors of both OS and CSS, while radiation dose was a significant predictor for OS and indicated a trend (p = 0.07) for CSS. A dose of 70 Gy combined with hormonal treatment improves PSA failure free survival and survival in localised prostate cancer compared with doses of 64–66 Gy.

Long-term clinical outcomes of 420 consecutive prostate cancer patients in a single institute.

This study was undertaken to reveal the trends of prostate cancer and the outcome of treatment modalities for each disease stage in patients in a single institute over a 10-year period. From January 1994 through December 2003, 420 consecutive patients with previously untreated and histologically confirmed prostate cancer were analyzed for annual distributions of disease stages and treatment modalities and for long-term clinical progression-free survival, prostate cancer-specific survival, and prostate-specific antigen (PSA) failure-free survival rates for each stage and treatment modality. Annual trends showed that the number of patients, especially those with clinically localized cancer, increased dramatically. The 5-year disease-specific survival rates for patients with clinically localized disease were 100 percent for all treatment modalities, including hormonal therapy alone. Patients with PSA levels less than 10 ng/ml showed an 81 percent 5-year PSA failure-free survival rate with radical prostatectomy. Stage C patients treated by surgery or radiation-based therapy with concomitant hormonal therapy obtained 93 percent and 100 percent cause-specific survival rates, respectively, and those treated by hormonal therapy alone showed a 79 percent rate. The number of patients with localized prostate cancer was increasing in this decade. While long-term hormonal therapy alone was highly efficient in controlling localized prostate cancer, radical therapies in conjunction with neo-adjuvant hormonal therapy produced better survival rates in cases of locally advanced disease.

The impact of a delay in initiating radiation therapy on prostate‐specific antigen outcome for patients with clinically localized prostate carcinoma

To determine whether a delay in initiating external beam radiation therapy (RT) following diagnosis could impact prostate-specific antigen (PSA) outcome for patients with localized prostate cancer, 460 patients, who received 3D conformal RT to a median dose of 70.4 Gy for clinically localized prostate cancer between 1992 and 2001, were studied. The primary endpoint was PSA failure (American Society for Therapeutic Radiology and Oncology definition). Estimates of PSA control were made using the Kaplan-Meier method. Delay was defined as the time between diagnosis and the start of RT. Risk groups were defined based on known predictors of PSA outcome, namely, baseline PSA level, clinical T-category, Gleason score, and percentage of biopsy cores positive for tumor. Cox multivariate regression analysis was used to determine the ability of treatment delay to predict time to PSA failure after adjusting for the other known predictors. Treatment delay independently predicted time to PSA failure following diagnosis for high-risk (Adjusted Hazard Ratio = 1.08 per month; P = 0.029) but not low-risk patients (P = 0.31). Patients with high-risk disease (n = 240) had 5-year estimates of PSA failure-free survival of 55% versus 39% (Plog-rank = 0.014) for those with delay < 2.5 months versus > or = 2.5 months respectively. The median delay was 2.5 months. Treatment delay adversely affected PSA outcome for high-risk patients but not for low-risk patients following RT.