Faculty Bibliography

BACKGROUND: Prostate cancer (PCa) racial disparity studies typically focus on survival differences after curative treatment. The authors of this report hypothesized that comparing mortality rates between African American (AA) and Caucasian American (CA) patients who deferred primary treatment for clinically nonmetastatic PCa may provide a better assessment of the impact of race on the natural course of PCa. METHODS: The pathology database of the New York Veterans Administration Medical Center (VAMC), an equal access-of-care facility, was searched for patients with biopsy-proven PCa. Inclusion criteria included 1) no evidence of metastatic disease or death within 3 years after diagnosis, 2) no primary treatment, and 3) a minimum of 5 years of follow-up for survivors. RESULTS: In total, 518 patients met inclusion criteria between 1990 and 2005. AA patients were younger (P = .02) and had higher median prostate-specific antigen (PSA) levels (P = .001) at the time of diagnosis compared with CA patients. In a multivariate model, higher Gleason score and PSA level were associated with increased mortality (P = .001 and P = .03, respectively), but race was not a predictor of death from PCa. CONCLUSIONS: The current data suggested that race did not have a major impact on survival in patients with PCa who deferred primary treatment for clinically nonmetastatic disease. Cancer 2011. (c) 2011 American Cancer Society

Study Type - Diagnostic (validating cohort) Level of Evidence 1b What's known on the subject? and What does the study add? Nadir Ultrasensitive PSA levels has some value for predicting BCR following RD. AccuPSA assays lower limit of PSA quantification of <0.01 pg/ml greatly enhances sensitivity and specificity of nadir PSA to predict BCR following RP. Our pilot study shows an AccuPSA of 3 pg/ml has a sensitory and specificity of 100% and 75% respectively for predicting 5 year BCR following RP. OBJECTIVES * To conduct a proof of concept study to evaluate a novel digital single molecule immunoassay (AccuPSA(TM) ) that detects prostate-specific antigen (PSA) a thousandfold more sensitively than current PSA detection methods. * To determine the ability of the AccuPSA(TM) assay to predict 5-year biochemical recurrence (BCR)-free survival after radical prostatectomy (RP). PATIENTS AND METHODS * A total of 31 frozen serum specimens were obtained from specimen logs maintained at New York University Langone Medical Center and the Johns Hopkins University School of Medicine on men who had undergone RP. Those men without evidence of BCR had a minimum of 5 years' PSA follow-up. * In all cases, preoperative and pathological information were available, as was a serum specimen 3-6 months after RP, with a PSA level of <0.1 ng/mL measured by conventional PSA methods at the time of serum collection. * Specimens were tested using the AccuPSA(TM) method. * A Cox proportional hazard model and Kaplan-Meier analysis were used to determine whether AccuPSA(TM) predicted the risk of BCR. RESULTS * Overall, 11/31 (35.5%) men developed BCR. * Mean AccuPSA(TM) nadir levels were significantly different (P < 0.001) between the non-BCR group (2.27 pg/mL) and the BCR group (46.99 pg/mL). * Using a multivariate Cox proportional hazard model, AccuPSA(TM) nadir level was a significant predictor of BCR-free survival (P < 0.01). * Kaplan-Meier analysis of up to 5 years follow-up showed that 100% of men with AccuPSA(TM) nadir values <3 pg/mL did not develop BCR, whereas 62.5% of men with values >3 pg/mL developed BCR (P= 0.00024). * The sensitivity, specificity, positive predictive value and negative predictive value of the AccuPSA(TM) method was 100%, 75%, 69% and 100%, respectively. CONCLUSIONS * AccuPSA(TM) assay predicts 5-year BCR- free survival after RP. * Identifying a reliable predictor of BCR soon after RP has important implications for frequency of PSA testing, selection of candidates for adjuvant therapy, and reassuring a large subset of men that they are not at risk of recurrence. * Larger studies are needed to validate these findings

PURPOSE: To assess the utility of apparent diffusion coefficient (ADC) values obtained from diffusion-weighted imaging (DWI) in distinguishing high-grade bladder cancer with and without metastatic disease. MATERIALS AND METHODS: Seventeen patients with histologically confirmed high-grade bladder cancer who underwent pelvic magnetic resonance imaging (MRI) at 1.5T including DWI using b-values of 0, 400, and 800 sec/mm(2) were assessed. Histologic findings and follow-up imaging were used to establish the reference standard in terms of metastatic disease. Two radiologists independently recorded ADC of all lesions following a training session, with their results averaged. Mann-Whitney U-test, receiver operating characteristic (ROC) curve analysis and intraclass correlation coefficient (ICC) were used for data analysis. RESULTS: Metastatic disease was characterized as present or absent in eight and nine patients, respectively. ADC was significantly lower among cases with metastatic disease than among cases without metastatic disease, both within the entire cohort (1.07 +/- 0.18 x 10(-3) mm(2) /s vs. 1.45 +/- 0.22 x 10(-3) mm(2) /s; P = 0.002) and within the subset of patients with muscle-invasive tumor (1.06 +/- 0.19 x 10(-3) mm(2) /s vs. 1.45 +/- 0.23 x 10(-3) mm(2) /s; P = 0.017). Area under the ROC curve for identifying metastatic disease using ADC was 0.944, with optimal threshold of 1.21 x 10(-3) mm(2) /s, which was associated with a sensitivity of 87.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 90.0%. Interreader agreement for ADC was excellent (ICC = 0.91). CONCLUSION: In this preliminary study, ADC was significantly different between cases of high-grade urothelial carcinoma of the bladder with and without metastatic disease. These results may have value in assessing the metastatic potential of patients with localized high-grade tumors of the bladder. J. Magn. Reson. Imaging 2012;. (c) 2012 Wiley Periodicals, Inc.

PURPOSE: We identified histological differences between prostate cancer foci that are detected and missed using multiparametric magnetic resonance imaging.MATERIALS AND METHODS: A total of 49 patients who underwent multiparametric magnetic resonance imaging, including T2-weighted imaging, including diffusion weighted imaging and dynamic contrast enhanced imaging, before prostatectomy were enrolled in the study. One radiologist identified areas highly suspicious for tumor. One pathologist identified and categorized tumors in terms of size, Gleason score, solid tumor growth, intermixed benign glands, loose stroma, desmoplastic stroma and a high malignant epithelium-to-stroma ratio. Differences between detected and missed tumors were assessed using logistic regression analyses based on generalized estimating equations for correlated data. RESULTS: All histological features showed significant differences between detected and missed tumors on multiparametric magnetic resonance imaging (p<0.0001). Independent predictors of detection on multivariate analysis were size (OR 5.38, p=0.0077), Gleason score (OR 5.12, p=0.0094) and solid growth (OR 17.83, p<0.0001). Size, Gleason score and loose stroma were significant predictors of identification with diffusion weighted imaging on univariate analysis (p≤0.0245), while Gleason score (OR 17.05, p=0.0212) and solid growth (OR 34.90, p=0.0103) were independent predictors of identification with diffusion weighted imaging on multivariate analysis. Identification with T2-weighted imaging was associated with size and Gleason score (p≤0.01876). Identification with dynamic contrast enhanced imaging was associated with intermixed benign epithelium, loose stroma and a high malignant epithelium-to-stroma ratio (p≤0.0499). No combination of features served as independent predictors on multivariate analysis for T2-weighted imaging or dynamic contrast enhanced imaging. CONCLUSIONS: There are fundamental histological differences between detected and missed prostate tumors using magnetic resonance imaging. Insights into these differences may facilitate the prospective role of magnetic resonance imaging in counseling and treatment selection for patients with prostate cancer