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Hopkins, MD, United States

Sundi D.,Brady Institute of Urology | Carter H.B.,Brady Institute of Urology | Ross A.E.,Brady Institute of Urology | Epstein J.I.,Johns Hopkins Medical Institutions | Schaeffer E.M.,Johns Hopkins Medical Institutions
Journal of Urology | Year: 2014

Purpose: Of men with very low risk prostate cancer at biopsy recent evidence shows that black American men are at greater risk for adverse oncologic outcomes after radical prostatectomy. We studied radical prostatectomy specimens from black and white men at very low risk to determine whether there are systematic pathological differences. Materials and Methods: Radical prostatectomy specimens were evaluated in men with National Comprehensive Cancer Network® (NCCN) very low risk prostate cancer. At diagnosis all men underwent extended biopsy sampling (10 or more cores) and were treated in the modern Gleason grade era. We analyzed tumor volume, grade and location in 87 black and 89 white men. For each specimen the dominant nodule was defined as the largest tumor with the highest grade. Results: Compared to white men, black men were more likely to have significant prostate cancer (61% vs 29%), Gleason 7 or greater (37% vs 11%, each p <0.001) and a volume of greater than 0.5 cm 3 (45% vs 21%, p = 0.001). Dominant nodules in black men were larger (median 0.28 vs 0.13 cm3, p = 0.002) and more often anterior (51% vs 29%, p = 0.003). In men who underwent pathological upgrading the dominant nodule was also more frequently anterior in black than in white men (59% vs 0%, p = 0.001). Conclusions: Black men with very low risk prostate cancer at diagnosis have a significantly higher prevalence of anterior cancer foci that are of higher grade and larger volume. Enhanced imaging or anterior zone sampling may detect these significant anterior tumors, improving the outcome in black men considering active surveillance. © 2014 by American Urological Association Education Research, Inc.

Sundi D.,Brady Institute of Urology | Wang V.M.,Brady Institute of Urology | Pierorazio P.M.,Brady Institute of Urology | Han M.,Brady Institute of Urology | And 6 more authors.
Prostate Cancer and Prostatic Diseases | Year: 2014

Background:Outcomes in men with National Comprehensive Cancer Network (NCCN) high-risk prostate cancer (PCa) can vary substantially - some will have excellent cancer-specific survival, whereas others will experience early metastasis even after aggressive local treatments. Current nomograms, which yield continuous risk probabilities, do not separate high-risk PCa into distinct sub-strata. Here, we derive a binary definition of very-high-risk (VHR) localized PCa to aid in risk stratification at diagnosis and selection of therapy.Methods:We queried the Johns Hopkins radical prostatectomy database to identify 753 men with NCCN high-risk localized PCa (Gleason sum 8-10, PSA >20 ng ml -1, or clinical stage ≥T3). Twenty-eight alternate permutations of adverse grade, stage and cancer volume were compared by their hazard ratios for metastasis and cancer-specific mortality. VHR criteria with top-ranking hazard ratios were further evaluated by multivariable analyses and inclusion of a clinically meaningful proportion of the high-risk cohort.Results:The VHR cohort was best defined by primary pattern 5 present on biopsy, or ≥5 cores with Gleason sum 8-10, or multiple NCCN high-risk features. These criteria encompassed 15.1% of the NCCN high-risk cohort. Compared with other high-risk men, VHR men were at significantly higher risk for metastasis (hazard ratio 2.75) and cancer-specific mortality (hazard ratio 3.44) (P<0.001 for both). Among high-risk men, VHR men also had significantly worse 10-year metastasis-free survival (37% vs 78%) and cancer-specific survival (62% vs 90%).Conclusions:Men who meet VHR criteria form a subgroup within the current NCCN high-risk classification who have particularly poor oncological outcomes. Use of these characteristics to distinguish VHR localized PCa may help in counseling and selection optimal candidates for multimodal treatments or clinical trials. © 2014 Macmillan Publishers Limited All rights reserved.

Sundi D.,Brady Institute of Urology | Cohen J.E.,Brady Institute of Urology | Cole A.P.,Brady Institute of Urology | Neuman B.P.,University of Texas Health Science Center at San Antonio | And 6 more authors.
Prostate | Year: 2015

BACKGROUND. The use of multidisciplinary clinics (MDCs) for outpatient cancer evaluation is increasing. MDCs may vary in format, and data on whether MDCs change prostate cancer (PCa) care are limited. Here we report on the setup and design of a relatively new PCa MDC clinic. Because MDC evaluation was associated with a comprehensive re-evaluation of all patients' staging and risk stratification data, we studied the frequency of changes in PCa grade and stage upon MDC evaluation, which provides a unique estimate of the magnitude of pathology, radiology, and exam-based risk stratification in a modern tertiary setting. METHODS. In 2008-2012, 887 patients underwent consultation for newly diagnosed PCa at the Johns Hopkins Hospital (JHH) weekly MDC. In a same-day process, patients are interviewed and examined in a morning clinic. Examination findings, radiology studies, and biopsy slides are then reviewed during a noon conference that involves real-time collaboration among JHH attending specialty physicians: urologists, radiation oncologists, medical oncologists, pathologists, and radiologists. During afternoon consultations, attending physicians appropriate to each patient's eligible treatment options individually meet with patients to discuss management strategies and/or clinical trials. Retrospective chart review identified presenting tumor characteristics based on outside assessment, which was compared with stage and grade as determined at MDC evaluation. RESULTS. Overall, 186/647 (28.7%) had a change in their risk category or stage. For example, 2.9% of men were down-classified as very-low-risk, rendering them eligible for active surveillance. 5.7% of men thought to have localized cancer were up-classified as metastatic, thus prompting systemic management approaches. Using NCCN guidelines as a benchmark, many men were found to have undergone non-indicated imaging (bone scan 23.9%, CT/MRI 47.4%). The three most chosen treatments after MDC evaluation were external beam radiotherapy ± androgen deprivation (39.3%), radical prostatectomy (32.0%), and active surveillance/expectant management (12.9%). CONCLUSIONS. A once-weekly same-day evaluation that involves simultaneous data evaluation, management discussion, and patient consultations from a multidisciplinary team of PCa specialists is feasible. Comprehensive evaluation at a tertiary referral center, as demonstrated in a modern MDC setting, is associated with critical changes in presenting disease classification in over one in four men. © 2014 Wiley Periodicals, Inc.

Sundi D.,Brady Institute of Urology | Wang V.,Brady Institute of Urology | Pierorazio P.M.,Brady Institute of Urology | Han M.,Brady Institute of Urology | And 4 more authors.
Prostate | Year: 2014

BACKGROUND Men destined to have early biochemical recurrence (BCR) following radical prostatectomy (RP) may be optimal candidates for multimodal treatment. Here we identified pre-operative predictors of early BCR within a surgical cohort who recurred. METHODS An institutional prostate cancer (PCa) database containing over 20,000 patients was queried to identify 1,471 men who had BCR after RP, and pre-operative predictors of early versus late BCR were assessed. Early BCR was defined as recurrence within 1 year after RP. Within the recurrence cohort, those with National Comprehensive Cancer Network (NCCN) high-risk features were more likely to experience early BCR. Therefore, in all NCCN high-risk men in the database, we abstracted detailed pathologic biopsy data. Among 753 high-risk men, 41 alternate multivariable criteria were assessed for their ability to predict early BCR in crude and adjusted logistic regression models. RESULTS The criteria that best identified those likely to experience early BCR are primary Gleason pattern 5 on biopsy or ≥4 cores containing pattern 4 (odds ratio 3.17, P < 0.001). These criteria included 26.7% of NCCN high-risk men. Additionally, these criteria selected for men within the high-risk classification who were at significantly higher risk of subsequent metastasis (adjusted hazard ratio 3.04, P < 0.001) and cancer-specific death (adjusted hazard ratio 3.27, P < 0.001). CONCLUSIONS In men with PCa who present with high-risk features, pre-operative criteria have the ability to discriminate the subgroup most likely to experience early BCR after RP. Men at risk for early disease recurrence may be the most suitable candidates for multimodal therapy.© 2014 Wiley Periodicals, Inc.

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