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INTRODUCTION AND OBJECTIVES: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR. MATERIAL AND METHODS: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS. In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions. RESULTS: The following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors > 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001.

Introduction and objectives: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR. Material and methods: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS. In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions. Results: The following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors >= 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001

BACKGROUND: Several randomized controlled trials assessed the outcomes of patients treated with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP). The majority of them included mainly low and intermediate risk prostate cancer (PCa) without specifically assessing PCa-related death (PCRD). Thus, there is a lack of knowledge regarding a possible effect of NHT on PCRD in the high-risk PCa population. We aimed to analyze the effect of NHT on PCRD in a multicenter high-risk PCa population treated with RP, using a propensity-score adjustment. METHODS: This is a retrospective multi-institutional study including patients with high-risk PCa defined as: clinical stage T3-4, PSA >20 ng ml-1 or biopsy Gleason score 8-10. We compared PCRD between RP and NHT+RP using competing risks analysis. Correction for group differences was performed by propensity-score adjustment. RESULTS: After application of the inclusion/exclusion criteria, 1573 patients remained for analysis; 1170 patients received RP and 403 NHT+RP. Median follow-up was 56 months (interquartile range 29-88). Eighty-six patients died of PCa and 106 of other causes. NHT decreased the risk of PCRD (hazard ratio (HR) 0.5; 95% confidence interval (CI) 0.32-0.80; P=0.0014). An interaction effect between NHT and radiotherapy (RT) was observed (HR 0.3; 95% CI 0.21-0.43; P<0.0008). More specifically, of patients who received adjuvant RT, those who underwent NHT+RP had decreased PCRD rates (2.3% at 5 year) compared to RP (7.5% at 5 year). The retrospective design and lack of specific information about NHT are possible limitations. CONCLUSIONS: In this propensity-score adjusted analysis from a large high-risk PCa population, NHT before surgery significantly decreased PCRD. This effect appeared to be mainly driven by the early addition of RT post-surgery. The specific sequence of NHT+RP and adjuvant RT merits further study in the high-risk PCa population.

The goal of this project is to develop biopsy based assays to assess the probability that patients with a negative biopsy or with a prostate cancer (CaP) Gleason score 6 (GS6) biopsy actually have significant CaP of Gleason score 7 or higher which was missed during the biopsy evaluations due to insufficient sampling. In 2014, we considerably expanded the size of the discovery samples which will improve the robustness of biomarkers and developed methodologies for improving the detection of epigenetic modification in rare cells. Also, we tested several methods for multiplex analyses of transcriptome and DNA methylation changes. Further, we have secured additional funding which will allow us to expand transcriptome and epigenome profile of indolent and significant prostate tumors. Finally, we have applied for major grant initiatives which if funded, will help expanding the scope of this study through the use of nano-scale devices and quantum dot based assays. We are expecting the publications of our research results in the coming year., The original document contains color images.

The goal of this project is to develop biopsy based assays to assess the probability that patients with a negative biopsy or with a prostate cancer (CaP) Gleason score 6 (GS6) biopsy actually have significant CaP of Gleason score 7 or higher which was missed during the biopsy evaluations due to insufficient sampling. According to the DOD regulations, all research activities began after the approval of the research protocol by the HRPO at the end of March 2012. Since then, we have completed the transcriptomic profiling of the samples described in the original protocol. Furthermore, through additional funding and collaborations, we have significantly expanded the size and scope of the samples for genomic profiling. Transcriptomic profile (RNA-seq) of the expanded set of samples has been generated and mapped. We encountered some challenges in generating RRBS libraries from LCM samples which we overcame and we expect to have the RRBS data of the expanded set available shortly. Validation experiments were started by two new members of our team and are proceeding rapidly. Also, with the assistance of the biostatisticians in our group, case selection for all steps of the project is completed. Other research engagements funded separately, such as investigations of DNA-BPDE adducts and specific non-coding RNA in the benign tissues have promise in improving the accuracy of assays developed in this proposal. We are encouraged by our progress and are excited about the prospects of this research in improving the care of patients at risk of prostate cancer.

The goal of this project is to develop biopsy based assays to assess the probability that patients with a negative biopsy or with a prostate cancer (CaP) Gleason score 6 (GS6) biopsy actually have significant CaP of Gleason score 7 or higher which was missed during the biopsy evaluations due to insufficient sampling. Based on the concepts of the CaP field effect , this goal will be achieved by gene expression and epigenetic analysis of preneoplastic lesions and non-cancerous areas of prostate tissues from patients with CaP and benign prostate tissues from patients free of CaP. According to the DOD regulations, all research activities began after the approval of the research protocol by the HRPO in March 20 2012. Since then, we have identified the appropriate cases for the study and completed collection by laser captured microdissection (LCM) of all but two of the samples needed for genomic profiling. The collection of samples by LCM was an important part of the experiments in the first year of this project. Procedures for the collection of benign prostate tissues from patients free of CaP have been established. Internally funded collaborations have been established which will enhance the chances of success in this project by expanding the scope of genomic profiling. Two 2012 publications describe our findings related to the CaP field effect. Encouraged by these findings, we are actively pursuing the objectives of this project.