Does true Gleason pattern 3 merit its cancer descriptor?

Nearly five decades following its conception, the Gleason grading system remains a cornerstone in the prognostication and management of patients with prostate cancer. In the past few years, a debate has been growing whether Gleason score 3 + 3 = 6 prostate cancer is a clinically significant disease. Clinical, molecular and genetic research is addressing the question whether well characterized Gleason score 3 + 3 = 6 disease has the ability to affect the morbidity and quality of life of an individual in whom it is diagnosed. The consequences of treatment of Gleason score 3 + 3 = 6 disease are considerable; few men get through their treatments without sustaining some harm. Further modification of the classification of prostate cancer and dropping the label cancer for Gleason score 3 + 3 = 6 disease might be warranted

Clinical and diagnostic assessment for therapeutic decisions in prostate cancer

Due to the heterogeneity of prostate cancer (PCa) outcomes, there is a need for individualized treatment plans based on clinical and cancer characteristics. Recent advances in sophisticated imaging modalities have improved the ability to stratify patients according to their risk of PCa diagnosis and progression. This, in turn, has positively influenced the clinical decision making process. However, there is also an overuse of diagnostic imaging in the evaluation of PCa patients. Baseline diagnostic and re-staging evaluations need to be indeed personalized, in order to maximize the results and reduce unnecessary, lengthy and costly procedures. The aim of this review was to critically evaluate current international guidelines in order to identify clinical and diagnostic markers that might help clinicians in the selection of the most appropriate imaging approach. For this aim, different imaging modalities were analyzed in patients with newly diagnosed PCa, focusing on local, nodal and distant staging. Every step of staging was taken into consideration based on patient individualized risk, as defined by routinely available clinical variables. Second, different imaging techniques were also reviewed in the context of relapse after primary treatment, highlighting their utility and impact in the clinical decision making process. This review focuses mainly on conventional established imaging techniques, with an eye also to novel approaches that still need to be validated on large patient series

Head-to-head comparison of lymph node density and number of positive lymph nodes in stratifying the outcome of patients with lymph node-positive prostate cancer submitted to radical prostatectomy and extended lymph node dissection

Objective: The aim of this study was to compare the predictive ability of lymph node density (LND) and number of positive lymph nodes in patients with prostate cancer and lymph node invasion. Materials and methods: We included 568 patients with lymph node invasion treated with radical prostatectomy and extended pelvic lymph node dissection between January 1990 and July 2011 at a single center. The Kaplan-Meier method and multivariable Cox regression models tested the association between the number of positive lymph nodes or LND and cancer-specific survival (CSS). The predictive accuracy of a baseline model was assessed using Harrell's concordance index and then compared with that of a model including either the number of positive nodes or LND. Results: The median number of positive lymph nodes was 2, whereas the median LND was 11.1%. At 5, 8, and 10 years, CSS rates were 92.5%, 83.9%, and 82.8%, respectively. At multivariahle analyses, number of positive lymph nodes and I,ND, considered as continuous variables, were independent predictors of CSS (all P <= 0.01). A 30% LND cutoff was found to be highly predictive of CSS (P = 0.004), and a cutoff of 2 positive nodes was confirmed to be a strong predictor of CSS (P = 0.02). The number of positive nodes and LND similarly, continuous or dichotomized, increased the accuracy for CSS predictions (0.68-0.69 vs. 0.61 of baseline model). LND cutoff of 30% increased the discrimination the most (0.69; +0.083). Conclusions: The number of positive lymph nodes and LND showed comparable discriminative power for long-term CSS predictions. A cutoff of 30% LND might be suggested for the selection of patients candidate for adjuvant systemic therapy, because it increased the model's discrimination the most. (C) 2014 Elsevier Inc. All rights reserved

Performance Characteristics of Computed Tomography in Detecting Lymph Node Metastases in Contemporary Patients with Prostate Cancer Treated with Extended Pelvic Lymph Node Dissection

Background: Computed tomography (CT) is a commonly used noninvasive procedure for prostate cancer (PCa) staging. All previous studies addressing the ability of CT scan to predict lymph node invasion (LNI) were based on historical patients treated with limited pelvic lymph node dissection (PLND). Objective: Assess the value of CT in predicting LNI in contemporary PCa patients treated with extended PLND (ePLND). Design, setting, and participants: We evaluated 1541 patients undergoing radical prostatectomy and ePLND between 2003 and 2010 at a single center. All patients were preoperatively staged using abdominopelvic CT scan. All lymph nodes with a short axis diameter >= 10 mm were considered suspicious for metastatic involvement. Intervention: All patients underwent preoperative CT scan, radical retropubic prostatectomy, and ePLND, regardless of PCa features at diagnosis. Measurements: The performance characteristics of CT scan were tested in the overall patient population, as well as according to the National Comprehensive Cancer Network (NCCN) classification and according to the risk of LNI derived from a nomogram developed on an ePLND series. Logistic regression models tested the relationship between CT scan findings and LNI. Discrimination accuracy was quantified with the area under the curve. Results and limitations: Overall, a CT scan that suggested LNI was found in 73 patients (4.7%). Of them, only 24 patients (32.8%) had histologically proven LNI at ePLND. Overall, sensitivity, specificity, and accuracy of CT scan were 13%, 96.0%, and 54.6%, respectively. In patients with low-, intermediate-, or high-risk PCa according to NCCN classification, sensitivity was 8.3%, 96.3%, and 52.3%, respectively; specificity was 3.6%, 97.3%, and 50.5%, respectively; and accuracy was 17.9%, 94.3%, and 56.1%, respectively. Similarly, in patients with a nomogram-derived LNI risk >= 50%, sensitivity, specificity, and accuracy were only 23.9%, 94.7%, and 59.3%, respectively. At multivariable analyses, inclusion of CT scan findings did not improve the accuracy of LNI prediction (81.4% compared with 81.3%; p = 0.8). Lack of a central scan review represents the main limitation of our study. Conclusions: In contemporary patients with PCa, the accuracy of CT scan as a preoperative nodal-staging procedure is poor, even in patients with high LNI risk. Therefore, the need for and the extent of PLND should not be based on the results obtained by CT scan. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved

Selecting the Optimal Candidate for Adjuvant Radiotherapy After Radical Prostatectomy for Prostate Cancer: A Long-term Survival Analysis

Background: The role of adjuvant radiotherapy (ART) after radical prostatectomy (RP) on survival of patients with prostate cancer (PCa) is still controversial. Objective: We tested the impact of ART on cancer-specific mortality (CSM) and overall mortality (OM) in PCa patients according to pathologic PCa features. Design, setting, and participants: We evaluated 1049 PCa patients treated with RP and extended pelvic lymph node dissection alone or in combination with adjuvant treatments between 1998 and 2008. All patients had positive surgical margins and/or pT3/pT4 disease with or without positive lymph nodes. Outcome measurements and statistical analysis: Cox regression analyses tested the relationship between pathologic characteristics and CSM rates. Independent predictors of survival were used to develop a novel risk score based on the number of risk factors. Finally, Cox regression models tested the relationship between ART and survival according to the number of risk factors. Results and limitations: On multivariable analyses, only pathologic Gleason score >= 8, pT3b/T4 stage, and presence of positive lymph nodes represented independent predictors of CSM (all p = 0.4). Conversely, in patients with a risk score >= 2, ART was associated with lower CSM and OM rates (all p = 0.006). The observational nature of the cohort represents a limitation of the study. Conclusions: ART significantly improved survival only in patients with at least two of the following pathologic features at RP: Gleason score >= 8, pT3/pT4 disease, and positive lymph nodes. These patients represent the ideal candidates for ART after RP. (c) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved