Biochemical Recurrence In Multivariate Analysis Research Articles

Dose compliance of estramustine phosphate in neoadjuvant chemohormonal therapy combined with degarelix acetate predicts the biochemical recurrence in patients with very high-risk prostate cancer who underwent robot-assisted radical prostatectomy.

The objective of this study is to evaluate the safety and efficacy of neoadjuvant degarelix acetate and low-dose estramustine phosphate for high-/very high-risk prostate cancer. Overall, 187 patients diagnosed with National Comprehensive Cancer Network high-/very high-risk cTanyN0M0 localized prostate cancer who consented to undergo robot-assisted radical prostatectomy after receiving neoadjuvant chemohormonal therapy for 6 months were prospectively enrolled between December 2017 and March 2023. Adverse events, perioperative and histopathological outcomes, and biochemical recurrence-free survival rates were examined. Survival analysis compared the estramustine phosphate completion and reduction groups. Thirty-six patients discontinued neoadjuvant therapy in <5 months owing to adverse events (n = 34) or other reasons (n = 2). Eleven were excluded for being in the postoperative castration range. Of the 140 patients who underwent surgery, 124 continued with two tablets of estramustine phosphate and 16 with one tablet. Overall, 82 patients were very high-risk. Histopathological outcomes were significantly worse in the very high-risk group than those in the high-risk group. Very high-risk status and estramustine phosphate reduction were significant factors in biochemical recurrence in multivariate analysis. The biochemical recurrence-free survival rate in very high-risk patients was significantly lower in the estramustine phosphate dose reduction group than in the completion group but not significant in high-risk patients. Major adverse events were anemia (n = 174), elevated transaminase levels (n = 68), and deep vein thrombosis (n = 24). Severe adverse events included acute coronary syndrome (n = 4) and pulmonary embolism (n = 3). Dose compliance with estramustine phosphate predicted biochemical recurrence in patients with very high-risk prostate cancer undergoing robot-assisted radical prostatectomy with neoadjuvant chemohormonal therapy.

Positive STAT5 Protein and Locus Amplification Status Predicts Recurrence after Radical Prostatectomy to Assist Clinical Precision Management of Prostate Cancer

A significant fraction of prostate cancer patients experience post-radical prostatectomy (RP) biochemical recurrence (BCR). New predictive markers are needed for optimizing postoperative prostate cancer management. STAT5 is an oncogene in prostate cancer that undergoes amplification in 30% of prostate cancers during progression. We evaluated the significance of a positive status for nuclear STAT5 protein expression versus STAT5 locus amplification versus combined positive status for both in predicting BCR after RP in 300 patients. Combined positive STAT5 status was associated with a 45% disadvantage in BCR in Kaplan-Meier survival analysis in all Gleason grade patients. Patients with Gleason grade group (GG) 2 and 3 prostate cancers and combined positive status for STAT5 had a more pronounced disadvantage of 55% to 60% at 7 years after RP in univariate analysis. In multivariate analysis, including the Cancer of the Prostate Risk Assessment Postsurgical nomogram (CAPRA-S) variables, combined positive STAT5 status was independently associated with a shorter BCR-free survival in all Gleason GG patients (HR, 2.34; P = 0.014) and in intermediate Gleason GG 2 or 3 patients (HR, 3.62; P = 0.021). The combined positive STAT5 status improved the predictive value of the CAPRA-S nomogram in both ROC-AUC analysis and in decision curve analysis for BCR. Combined positive status for STAT5 was independently associated with shorter disease-free survival in univariate analysis and was an independent predictor for BCR in multivariate analysis using the CAPRA-S variables in prostate cancer. Our results highlight potential for a novel precision medicine concept based on a pivotal role of STAT5 status in improving selection of prostate cancer patients who are candidates for early adjuvant interventions to reduce the risk of recurrence.

Stage-specific embryonic antigen-4 is a histological marker reflecting the malignant behavior of prostate cancer

Stage-specific embryonic antigen-4 (SSEA-4), a specific marker for pluripotent stem cells, plays an important role in the malignant behavior of several cancers. Here, SSEA-4 expression was evaluated by immunohistochemistry using monoclonal antibody RM1 specific to SSEA-4 in 181 and 117 prostate cancer (PC) specimens obtained by biopsy and radical prostatectomy (RP), respectively. The relationships between SSEA-4 expression in cancer cells or the presence of SSEA-4-positive tumor-infiltrating immune cells (TICs) and clinicopathological parameters were analyzed. SSEA-4 expression in cancer cells was significantly associated with Gleason score, local progression, and lymph node and distant metastasis. In RP specimens, high SSEA-4 expression in cancer cells and the presence of SSEA-4-positive TICs were significant predictors of pT3, i.e., invasion and worse biochemical recurrence (BCR) after RP, respectively, in univariate analysis. In contrast, combination of high SSEA-4 expression in cancer cells and the presence of SSEA-4-positive TICs was an independent predictor for pT3 and BCR in multivariate analysis. Biologically this combination was also independently associated with suppression of apoptosis. Thus, the co-expression of SSEA-4 in cancer cells and TICs may have crucial roles in the malignant aggressiveness and prognosis of PC. Invasive potential and suppression of apoptosis may be linked to SSEA-4 expression.

Where is the limit of prostate cancer biomarker research? Systematic investigation of potential prognostic and diagnostic biomarkers

BackgroundThe identification of appropriate biomarkers is essential to support important clinical decisions in patients with prostate cancer. The aim of our study was a systematic bioinformatical analysis of the mRNA expression of all genes available for the prostate adenocarcinoma cohort of The Cancer Genome Atlas (TCGA), regarding their potential prognostic and diagnostic role.MethodsThe study cohort comprises 499 patients (TCGA prostate cancer cohort). mRNA expression data were available for approx. 20,000 genes. The bioinformatical statistical pipeline addressed gene expression differences in tumor vs. benign prostate tissue (including gene set enrichment analysis, GSEA) in samples from tumors with different aggressivenesses (Gleason score), as well as prognostic values in multistep survival analyses.ResultsAmong all genes analyzed, 1754 were significantly downregulated and 1553 genes were significantly upregulated in tumor tissue. In GSEA, 16 of 30 top enriched biological processes were alterations of epigenetic regulation at different levels. Significant correlation with Gleason Score was evident for 8724 genes (range of Pearson r-values 0.09–0.43; all p < 0.05). In univariate Cox regression analyses, mRNA expression of 3571 genes showed statistically significant association with biochemical recurrence-free survival with a range of hazard ratios 0.3–3.8 (p-value 7.4e− 07 to 0.05). Among these, 571 genes were independently associated with biochemical recurrence in multivariate analysis. Access to the full database including results is provided as supplement.ConclusionsIn our systematic analysis we found a big number of genes of potential diagnostic and prognostic value, many of which have not been studied in prostate cancer to date. Due to the comprehensive nature of this analysis and free access to the results, this study represents a reference database for prostate cancer researchers which can be used as a powerful tool for validation purposes and planning of new studies.

Laparoscopic Radical Prostatectomy in Patients with High-Risk Prostate Cancer: Feasibility and Safety. Results of a Multicentric Study.

In Western countries about 25% of prostate cancer (PCa) are high-risk tumors at presentation and its treatment is still a matter of debate among urologists. When a surgical approach is preferred the use of a mininvasive tecnique is still difficult due to the lack of data supporting it in literature. The aim of this study is to evaluate feasibility and safety of laparoscopic radical prostatectomy (LRP) for high-risk PCa. The study included 1114 patients with high-risk PCa submitted to LRP between 1998 and 2014. High-risk patients were defined according to D'Amico classification. We collected functional and oncological long-term outcomes and evaluated with univariate and multivariate analyses the role of predictive factors for survival and biochemical recurrence (BR). Mean age at treatment was 62 ± 8 years; mean follow-up was 74 ± 50 months. We obtained an overall survival (OS) of 96.6% at a mean follow-up of 74 months (1076 patients) and a disease-free survival of 66.2% (737 patients). Age (p = 0.0006), pT (p < 0.0001), pN (p = 0.0018), and surgical margins (p = 0.0076) resulted as independent predictors for BR in multivariate analysis. pN (p = 0.0025) and Gs (p = 0.0003) are independent predictors for OS and cancer-specific survival in a univariate analysis; just the Gs results significant in the multivariate model. According to our encouraging data about oncological and functional outcomes we believe that radical prostatectomy represents an effective treatment for patients with high-risk PCa and that laparoscopy is a safe approach offering a mini-invasive alternative to open surgery.

Decreased expression of bone morphogenetic protein-2 is correlated with biochemical recurrence in prostate cancer: Immunohistochemical analysis

We evaluated the prognostic value of BMP-2 expression in prostate cancer tissue via immunohistochemistry in prostate cancer patients. From July 2007 to August 2010, radical prostatectomy specimens from 90 patients with clinically localized prostate cancer (mean age, 62.7 years, mean follow-up 90.4 months) were assessed for BMP-2 expression using immunohistochemistry. We used stepwise multivariate Cox regression models stratified by study to assess the independent effects of the predictive factors and estimated hazard ratios (HRs). There were significant differences in the baseline characteristics of Gleason score (GS) and biochemical recurrence (BCR) between the groups with decreased and normal BMP-2 expression. Univariate analysis revealed GS, T stage (≥T3), and decreased BMP-2 expression as significant predictive determinants of BCR. In addition, GS (7: HR 2.836, p = 0.022; ≥8: HR 3.506, p = 0.048) and decreased BMP-2 expression (HR 2.007, p = 0.047) were significantly correlated with BCR in multivariate analysis. Overall five-year BCR-free survival rates in the group with decreased BMP-2 expression were worse than those in the group with normal expression. Therefore, decreased BMP-2 expression in prostate cancer tissue was correlated with the prognostic factors for BCR-free survival in patients with prostate cancer.

Prediction of biochemical recurrence after radical prostatectomy with PI-RADS version 2 in prostate cancers: initial results.

To determine whether the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) helps predict biochemical recurrence (BCR) after radical prostatectomy for prostate cancer (PCa). We included 158 patients with PCa who underwent magnetic resonance imaging (MRI) and radical prostatectomy (RP). Clinical (prostate-specific antigen, greatest percentage of core, and percentage of positive core number), PI-RADSv2 score on MRI, and surgical parameters (Gleason score, extracapsular extension, seminal vesicle invasion, and tumour volume) were investigated. Univariate and multivariate analyses using Cox's proportional hazards model were performed to assess parameters predictive of BCR (two consecutive prostate specific antigens ≥0.2ng/ml). Kaplan-Meier survival curves were analyzed. The rate of BCR was 13.3% (21/158) after surgery (median follow-up, 25months; range, 12-36). No subject with a PI-RADS score <4 had BCR. In univariate analysis, all parameters were significant for BCR (p < 0.05), except seminal vesicle invasion (p = 0.254). Meanwhile, PI-RADS score was the only independent parameter for BCR in multivariate analysis (p < 0.05). Two-year, BCR-free survival post-RP was significantly lower for PI-RADS ≥4 (84.7-85.5%) than for PI-RADS <4 (100%; p < 0.05). As a preoperative imaging tool, PI-RADSv2 may be useful to predict BCR after radical prostatectomy for PCa. • No subject with PI-RADS <4 had BCR after RP • PI-RADSv2 was the only predictor of BCR in multivariate analysis • Two-year, BCR-free survival following RP was lower for PI-RADS≥4 than for PI-RADS<4 • Inter-rater agreement was good for PI-RADS ≥4 or not.

The feature of metabolic syndrome is a risk factor for biochemical recurrence after radical prostatectomy.

To examine the association between the features of metabolic syndrome (MetS) (obesity, hypertension, diabetes mellitus, and dyslipidemia) and the risk of biochemical recurrence (BCR) after radical prostatectomy in patients with prostate cancer. This study included 283 Japanese patients with localized prostate cancer who were treated with radical prostatectomy between 2008 and 2012. Their oncological outcomes and the prognostic significance of several clinicopathological factors, as well as the features of MetS, were analyzed. Of 283 men who underwent radical prostatectomy, 49 (17.2%) subsequently developed BCR with a median postoperative follow-up of 14.8 months. Among the clinicopathological factors, prostate-specific antigen (PSA) level at diagnosis, pathological stage, pathological Gleason score, and lymph-node involvement were independent risk factors for BCR in multivariate analysis. In addition, the number of metabolic risk factors was also an independent risk factor for BCR. The features of MetS were linked with poorer outcome after radical prostatectomy among Japanese men. Further investigations are needed to determine the effect of improving MetS on prostate cancer prognosis.

Biochemical Recurrence–free Survival After Robotic-assisted Laparoscopic vs Open Radical Prostatectomy for Intermediate- and High-risk Prostate Cancer

To compare biochemical recurrence (BCR)-free survival and predictors of BCR in intermediate-risk (IR) and high-risk (HR) patients undergoing robotic-assisted laparoscopic prostatectomy (RALP) vs open radical prostatectomy (ORP). We conducted a retrospective study on 1336 men with D'Amico IR or HR prostate cancer who underwent RALP or ORP between 2003 and 2009. Exclusion criteria were use of neoadjuvant therapy, <6 months of follow-up, and insufficient clinicopathologic data. We compared demographic, clinical, and pathologic variables between groups. Kaplan-Meier analysis was performed to compare the 5-year BCR-free survival between groups. Multivariate models were developed to determine whether surgical approach influences BCR. A total of 979 IR and HR patients (237 ORP and 742 RALP patients) met inclusion criteria. Median follow-up was shorter for RALP (43 vs 63 months; P<.001). ORP patients had a higher median prostate-specific antigen level (7.9 vs 6.7 ng/mL; P<.002), significantly more Gleason sum 8-10 tumors, and more adverse pathologic features overall. There was no difference in positive surgical margins between groups. Pathologic features including extraprostatic extension, seminal vesicle involvement, lymph node involvement, pathologic Gleason sum, and positive surgical margin were significant independent predictors of BCR in multivariate analysis. Surgical approach (RALP vs ORP) did not predict BCR when controlling for other known predictors of BCR. Among IR and HR prostate cancer patients, the oncologic outcomes are similar between RALP and ORP. Not surprisingly, adverse pathologic features are harbingers of BCR.

MP45-17 SIGNIFICANT ASSOCIATION BETWEEN ABO BLOOD GROUP AND BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized III1 Apr 2014MP45-17 SIGNIFICANT ASSOCIATION BETWEEN ABO BLOOD GROUP AND BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY Yoshio Ohno, Makoto Ohori, Jun Nakashima, Hidenori Okubo, Yoshihiro Nakagami, Takeshi Hashimoto, Takeshi Kashima, Riu Hamada, Kunihiko Yoshioka, and Masaaki Tachibana Yoshio OhnoYoshio Ohno More articles by this author , Makoto OhoriMakoto Ohori More articles by this author , Jun NakashimaJun Nakashima More articles by this author , Hidenori OkuboHidenori Okubo More articles by this author , Yoshihiro NakagamiYoshihiro Nakagami More articles by this author , Takeshi HashimotoTakeshi Hashimoto More articles by this author , Takeshi KashimaTakeshi Kashima More articles by this author , Riu HamadaRiu Hamada More articles by this author , Kunihiko YoshiokaKunihiko Yoshioka More articles by this author , and Masaaki TachibanaMasaaki Tachibana More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1214AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Recent studies have demonstrated associations among the ABO blood group, risk, and prognosis in various diseases. However, to date, few studies have investigated the prognostic significance of the ABO blood group in prostate cancer. The aim of this study was to investigate the association of the ABO blood group with biochemical recurrence (BCR) after radical prostatectomy (RP). Methods We reviewed 719 patients who underwent RP for clinical T1–3N0M0 prostate cancer at our institution between 2000 and 2010. Patients who had neoadjuvant and/or adjuvant therapy were excluded from this study. As a result, a total of 592 patients were included for analysis in the present study. The associations among the ABO blood group, clinicopathologic factors, and BCR were analyzed using univariate and multivariate analyses. Results With a mean follow-up period of 67.3 months, 183 patients (30.9%) experienced BCR, with a 5-year BCR-free rate of 66.1%. Among the clinicopathologic characteristics, only surgical margin status was observed to significantly differ between patients with different ABO blood groups (A vs. B, P = 0.005; AB vs. B, P = 0.007). In univariate analyses, a higher serum prostate-specific antigen (PSA) level at diagnosis, extracapsular extension, a positive surgical margin, seminal vesicle invasion, lymphovascular invasion, and a higher Gleason score (GS ≥8) in the RP specimen were significantly associated with BCR. Although not a significant factor in univariate analysis (P = 0.131), the ABO blood group, in addition to the serum PSA level, extracapuslar extension, positive surgical margin, seminal vesicle invasion, and Gleason score, was an independent predictor of BCR in multivariate analysis. Hazard ratio and 95% confidence intervals for BCR according to the ABO blood group were shown in the Figure. Blood type O patients demonstrated a significantly lower risk of BCR than type A patients (HR, 0.624; 95%CI, 0.432–8211;0.901; P = 0.012). Conclusions The ABO blood group was significantly associated with BCR in prostate cancer patients who underwent RP. In particular, blood type O is significantly associated with a decreased risk of BCR after RP. Further studies are needed to clarify the nature of this association. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e466 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Yoshio Ohno More articles by this author Makoto Ohori More articles by this author Jun Nakashima More articles by this author Hidenori Okubo More articles by this author Yoshihiro Nakagami More articles by this author Takeshi Hashimoto More articles by this author Takeshi Kashima More articles by this author Riu Hamada More articles by this author Kunihiko Yoshioka More articles by this author Masaaki Tachibana More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

DNA Methylation Signatures for Prediction of Biochemical Recurrence After Radical Prostatectomy of Clinically Localized Prostate Cancer

Diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, causing overtreatment of indolent PC and risk of delayed treatment of aggressive PC. Here, we identify six novel candidate DNA methylation markers for PC with promising diagnostic and prognostic potential. Microarray-based screening and bisulfite sequencing of 20 nonmalignant and 29 PC tissue specimens were used to identify new candidate DNA hypermethylation markers for PC. Diagnostic and prognostic potential was evaluated in 35 nonmalignant prostate tissue samples, 293 radical prostatectomy (RP) samples (cohort 1, training), and 114 malignant RP samples (cohort 2, validation) collected in Denmark, Switzerland, Germany, and Finland. Sensitivity and specificity for PC were evaluated by receiver operating characteristic analyses. Correlations between DNA methylation levels and biochemical recurrence were assessed using log-rank tests and univariate and multivariate Cox regression analyses. Hypermethylation of AOX1, C1orf114, GAS6, HAPLN3, KLF8, and MOB3B was highly cancer specific (area under the curve, 0.89 to 0.98). Furthermore, high C1orf114 methylation was significantly (P < .05) associated with biochemical recurrence in multivariate analysis in cohort 1 (hazard ratio [HR], 3.10; 95% CI, 1.89 to 5.09) and was successfully validated in cohort 2 (HR, 3.27; 95% CI, 1.17 to 9.12). Moreover, a significant (P < .05) three-gene prognostic methylation signature (AOX1/C1orf114/HAPLN3), classifying patients into low- and high-methylation subgroups, was trained in cohort 1 (HR, 1.91; 95% CI, 1.26 to 2.90) and validated in cohort 2 (HR, 2.33; 95% CI, 1.31 to 4.13). We identified six novel candidate DNA methylation markers for PC. C1orf114 hypermethylation and a three-gene methylation signature were independent predictors of time to biochemical recurrence after RP in two PC patient cohorts.

Tumor Volume Adds Prognostic Value in Patients with Organ-Confined Prostate Cancer

This study was designed to assess the independent prognostic value of tumor volume (TV) and whether adding TV provides additional prognostic information for predicting biochemical recurrence (BCR) after radical prostatectomy. We reviewed the medical records of 1,129 patients who underwent radical prostatectomy between July 2005 and July 2011. TV was categorized as minimal (≤1.0 ml), moderate (1.1-5.0 ml), or extensive (>5.0 ml). Cox regression analysis was performed to identify independent predictors of BCR. The predictive accuracies of Cox's proportional hazard regression models with and without TV were quantified and compared using time-dependent receiver operating characteristic curve analysis. Increasing TV was associated with higher prostate specific antigen, pathological Gleason score, and pathologic tumor stage. TV was an independent predictor of BCR in multivariate analysis (p<0.001). When patients were stratified by organ-confined and nonorgan-confined tumor groups, TV remained an independent predictor of BCR in organ-confined tumors (p<0.001). In the nonorgan-confined tumor group, a significant difference was found only between extensive versus minimal TV (p=0.023). The predictive accuracy of the Cox regression model increased significantly by adding TV in organ-confined tumor group (0.748 vs. 0.704, p<0.05) but not in nonorgan-confined group (0.742 vs. 0.734, p>0.05). TV was an independent prognostic predictor of BCR in organ-confined prostate cancers and provided additional prognostic information with increased predictive accuracy. In contrast, TV did not increase the predictive accuracy in nonorgan-confined tumor. TV should be considered as a prognosticator in organ-confined tumors.

Abstract 649: A three-gene DNA methylation signature for prediction of biochemical recurrence after radical prostatectomy of clinically localized prostate cancer.

Abstract Purpose: Diagnostic and prognostic tools for prostate cancer (PC) are suboptimal causing overtreatment of indolent PC and risk of delayed treatment of aggressive PC. Here, we identify six novel candidate DNA methylation markers for PC with promising diagnostic and prognostic potential. Methods: Microarray-based screening and bisulfite sequencing of 20 non-malignant and 29 PC tissue specimens were used to identify new candidate DNA hypermethylation markers for PC. Diagnostic and prognostic potential was evaluated in 35 formalin-fixed paraffin-embedded (FFPE) nonmalignant prostate tissue samples, 293 FFPE malignant radical prostatectomy (RP) samples (cohort 1), and 148 fresh-frozen malignant RP samples (cohort 2) collected in Denmark, Switzerland, Germany, and Finland. Sensitivity and specificity for PC was evaluated by receiver operating characteristic analyses. Correlations between DNA methylation levels and biochemical recurrence were assessed by log rank tests as well as uni- and multivariate cox regression analyses. A methylation-based prognostic model was developed in cohort 1 and validated in cohort 2. Results: Hypermethylation of AOX1, C1orf114, GAS6, HAPLN3, KLF8, and MOB3B was highly cancer-specific (AUCs 0.89-0.98). Furthermore, a three-gene methylation signature (AOX1/C1orf114/HAPLN3) was developed in cohort 1 and validated in cohort 2. High AOX1/C1orf114/HAPLN3 methylation was significantly associated with biochemical recurrence in multivariate analysis (P&amp;lt;0.05) with hazard ratios of 1.79 (1.20-2.68) and 1.98 (1.02-3.83), respectively, independently of routine clinicopathological variables in both cohorts. Conclusion: We identified six novel candidate DNA methylation markers for PC and developed a three-gene methylation signature, which was an independent predictor of time to biochemical recurrence after RP in two PC patient cohorts. Citation Format: Christa Haldrup, Kamilla Mundbjerg, Else Marie Vestergaard, Philippe Lamy, Peter Wild, Wolfgang A. Schulz, Christian Arsov, Michael Borre Borre, Søren Høyer, Torben F. Ørntoft, Karina D. Sørensen. A three-gene DNA methylation signature for prediction of biochemical recurrence after radical prostatectomy of clinically localized prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 649. doi:10.1158/1538-7445.AM2013-649

966 ONCOLOGIC OUTCOMES FOLLOWING ROBOTIC-ASSISTED LAPAROSCOPIC VS. OPEN RADICAL PROSTATECTOMY FOR INTERMEDIATE AND HIGH-RISK PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced (III)1 Apr 2013966 ONCOLOGIC OUTCOMES FOLLOWING ROBOTIC-ASSISTED LAPAROSCOPIC VS. OPEN RADICAL PROSTATECTOMY FOR INTERMEDIATE AND HIGH-RISK PROSTATE CANCER Chad Ritch, Daniel Barocas, Chaochen You, Alexandra May, S. Duke Herrell, Peter Clark, David Penson, Sam Chang, Michael Cookson, and Joseph Smith Chad RitchChad Ritch Nashville, TN More articles by this author , Daniel BarocasDaniel Barocas Nashville, TN More articles by this author , Chaochen YouChaochen You Nashville, TN More articles by this author , Alexandra MayAlexandra May Nashville, TN More articles by this author , S. Duke HerrellS. Duke Herrell Nashville, TN More articles by this author , Peter ClarkPeter Clark Nashville, TN More articles by this author , David PensonDavid Penson Nashville, TN More articles by this author , Sam ChangSam Chang Nashville, TN More articles by this author , Michael CooksonMichael Cookson Nashville, TN More articles by this author , and Joseph SmithJoseph Smith Nashville, TN More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.547AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent studies suggest that surgical intervention may confer a benefit over observation for intermediate-risk (IR) and high-risk (HR) prostate cancer patients. It is unclear if this benefit differs based on surgical approach. We compared biochemical recurrence (BCR) free survival as well as predictors of BCR in IR and HR patients undergoing robotic-assisted laparoscopic prostatectomy (RALP) vs. open radical prostatectomy (ORP). METHODS A retrospective review was performed on 1286 men with IR or HR prostate cancer (cT2b or higher, or clinical Gleason Sum (GS) ≥7, or pre-op PSA >10) who underwent either RALP or ORP between 2003 -2009. We excluded any patient who had neoadjuvant therapy, <6 months of follow-up or insufficient clinicopathological data. We compared demographic, clinical and pathologic variables between the groups. Kaplan-Meier analysis was performed to compare the 5-year BCR-free survival between groups. Multivariate models were developed to determine predictors of BCR. RESULTS A total of 631 IR and HR patients (422 RALP, 209 ORP) met inclusion criteria. Median age was 62.2 years and was similar between groups, while median follow-up was shorter for RALP compared to ORP (3.7 vs. 4.5 yrs, p<0.001). Median PSA and clinical GS were 7.5 ng/ml and 7, respectively. ORP patients had a higher median PSA (8.6 vs. 6.9 ng/ml) than RALP patients (p<0.01). ORP patients had significantly more pathological GS 8-10 tumors (38% vs. 21%, p<0.001). There was a higher proportion of seminal vesicle involvement (SVI) in the ORP group (25% vs. 15%, p<0.01). The positive margin rate was similar between groups. Overall, 176 patients (28%) experienced BCR during follow-up (108 RALP, 68 ORP). There was no significant difference in 5-year BCR-free survival between groups. Extracapsular extension, pGS, and PSM were significant independent predictors of BCR in multivariate analysis. CONCLUSIONS Among IR and HR prostate cancer patients, the oncologic outcomes are similar between RALP and ORP. Not surprisingly, adverse pathologic features are a harbinger of BCR and identify those patients in need of multimodal therapy. Future research should focus on ways to reduce clinical recurrence among these patients. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e396 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Chad Ritch Nashville, TN More articles by this author Daniel Barocas Nashville, TN More articles by this author Chaochen You Nashville, TN More articles by this author Alexandra May Nashville, TN More articles by this author S. Duke Herrell Nashville, TN More articles by this author Peter Clark Nashville, TN More articles by this author David Penson Nashville, TN More articles by this author Sam Chang Nashville, TN More articles by this author Michael Cookson Nashville, TN More articles by this author Joseph Smith Nashville, TN More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Biochemical outcomes after robot-assisted radical prostatectomy in patients with follow-up more than 5-years

In this study, we assessed biochemical outcomes after robot-assisted radical prostatectomy (RARP). Between July 2005 and November 2007, one hundred and seventy-six consecutive patients treated by RARP without neoadjuvant treatment were included in this study. All procedures were performed by a single surgeon and the median follow-up period was 60 months (interquartile range (IQR): 59-69). The median prostate specific antigen was 7.50ng ml(-1) (IQR: 5.14-11.45) and 39.2% of the patients were classified as intermediate risk and 15.3% were classified as high risk; on final pathological examination, 35.2% of the patients had non-organ confined disease and 37.5% and 14.2% had Gleason scores of 7 and 8-10, respectively. The biochemical recurrence (BCR)-free survival rates at 3 and 5 years were 85.6% and 81.2%, respectively. The 5-year BCR-free survival rates stratified by pathologic Gleason scores were 93.1% in Gleason scores of 6 or less, 74.5% in a Gleason score of 7, and 58.1% in Gleason scores of 8 or greater, respectively (P<0.001). When stratified by pathologic stage, the BCR-free survival rates were 89.8% in pT2 patients, 66.2% in pT3a patients, and 39.3% in pT3b patients at 5 years following RARP, respectively (P<0.001). Preoperative prostate-specific antigen (PSA), pathologic stage, postoperative Gleason score and surgical margin status were independently associated with BCR in multivariate analysis. In this study, we report biochemical outcomes after RARP with the longest follow-up periods to date in Asian men. We found that robotic surgery provided satisfactory biochemical outcomes, and that RARP is a safe and effective procedure in terms of oncologic outcomes.

Heat shock proteins 27, 60 and 70 as prognostic markers of prostate cancer

Heat shock proteins (HSPs) protect cells against stress-associated injury and are overexpressed in several malignant tumors. We aimed to investigate their value as prognostic markers in prostate cancer. A tissue microarray (TMA) was constructed of 289 prostate cancers from radical prostatectomy (RP) specimens with median follow-up of 48.9 months. Slides were immunostained for HSP27, HSP60 and HSP70. Intensity and extent of immunoreactivity (IR) and their product (IRp) was evaluated by two observers. The IRp of HSP27 and HSP60, but not of HSP70, significantly predicted biochemical recurrence (p=0.014, 0.034 and 0.160, respectively). Recurrence-free survival in patients with strong HSP27 and HSP60 staining was shorter than in those with weak expression (p=0.019 and 0.001, respectively). IRp of HSP27 and HSP60 correlated with Gleason score (p<0.01). HSP60 was an independent predictor of biochemical recurrence in multivariate analysis, including extraprostatic extension, margin status, seminal vesicle invasion and Gleason score. Weighted kappa for interobserver agreement of HSP27, HSP60 and HSP70 IR was 0.613-0.823 for intensity and 0.584-0.719 for IRp, but only 0.036-0.244 for extent, raising the question whether staining extent should be estimated on TMA. We conclude that HSP27 and HSP60 are predictors of biochemical recurrence after RP.