Faculty Bibliography

Male hormonal physiology plays an important role in the function and development of the prostate. Moreover, benign prostatic hyperplasia and prostate cancer, two common and bothersome conditions of the prostate, are also influenced by hormonal activity. This article reviews the existing data regarding these complex relationships.

PURPOSE: While major prostate cancer active surveillance (AS) programs recommend repeat testing such as PSA and prostate biopsy, compliance with such testing is unknown. Our objective was to determine whether men in the community receive the same intensity of AS testing as in prospective AS protocols. MATERIALS AND METHODS: We performed a retrospective cohort study of men aged >/=66 in the SEER-Medicare database diagnosed with prostate cancer from 2001-2009 who did not receive curative therapy in the year after diagnosis with >/=1 post-diagnosis prostate biopsy. We used multivariable-adjusted Poisson regression to determine the association between frequency of AS testing with patient demographics and clinical features. Among 1349 men with /=14 PSA and >/=2 biopsy), and at Johns Hopkins (>/=10 PSA and >/=4 biopsy). RESULTS: Among 5192 patients undergoing AS, >80% had >/=1 PSA test per year but <13% received biopsy beyond the first 2 years. MRI was rarely used during the study period. On multivariable analysis, recent diagnosis and higher income were associated with higher frequency of surveillance biopsy, while older age and greater comorbidity were associated with fewer biopsies. African American men underwent fewer PSAs but similar numbers of biopsies. During 5 years of AS, only 11.1% and 5.0% met the testing standards of the Sunnybrook/PRIAS and Johns Hopkins programs. CONCLUSIONS: In the community, very few elderly men receive the intensity of AS testing recommended by major prospective AS programs.; Key of Definition for Abbreviations: AS=active surveillance, PCa=prostate cancer, PSA=prostate specific antigen, MRI=magnetic resonance imaging, NCCN=National Comprehensive Cancer Network, PRIAS=Prostate Cancer Research International Active Surveillance, WW=watchful waiting.

OBJECTIVES: To evaluate the cancer detection rates (CDR) for men undergoing 12 core systematic prostate biopsy with negative prebiopsy mpMRI (NegMR). MATERIALS & METHODS: Clinical data from consecutive men undergoing prostate biopsy with prebiopsy 3T mpMRI from December 2011 to August 2014 were reviewed from an IRB approved prospective database. Prebiopsy mpMRI was read by a single radiologist and men with NegMR prior to biopsy were identified for this analysis. Clinical features, CDR, and NPV rates were summarized. RESULTS: Seventy five men underwent SPB with a NegMRI during the study period. For the entire cohort, men with no prior biopsy, men with prior negative biopsy, and men enrolled in active surveillance protocols, overall CDR was 18.7%, 13.8%, 8.0% and 38.1%, respectively, and detection of Gleason sum >/= 7 (GS>/=7) cancer was 1.3%, 0%, 4.0% and 0%, respectively. The NPV for all cancers was 81.3%, 86.2%, 92.0%, and 61.9%, and for GS>/=7 cancer was 98.7%, 100%, 96.0% and 100%, respectively. CONCLUSIONS: Negative prebiopsy mpMRI confers an overall NPV of 82% on 12 core biopsy for all cancer and 98% for GS>/=7. Based upon biopsy indication, these findings assist in prebiopsy risk stratification for detection of high risk disease and may provide guidance in the decision to pursue biopsy

BACKGROUND: The risk of biochemical recurrence (BCR) following radical prostatectomy for pathologic Gleason 7 prostate cancer varies according to the proportion of Gleason 4 component. OBJECTIVE: We sought to explore the value of several novel quantitative metrics of Gleason 4 disease for the prediction of BCR in men with Gleason 7 disease. DESIGN, SETTING, AND PARTICIPANTS: We analyzed a cohort of 2630 radical prostatectomy cases from 1990-2007. All pathologic Gleason 7 cases were identified and assessed for quantity of Gleason pattern 4. Three methods were used to quantify the extent of Gleason 4: a quantitative Gleason score (qGS) based on the proportion of tumor composed of Gleason pattern 4, a size-weighted score (swGS) incorporating the overall quantity of Gleason 4, and a size index (siGS) incorporating the quantity of Gleason 4 based on the index lesion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between the above metrics and BCR were evaluated using Cox proportional hazards regression analysis. RESULTS AND LIMITATIONS: qGS, swGS, and siGS were significantly associated with BCR on multivariate analysis when adjusted for traditional Gleason score, age, prostate specific antigen, surgical margin, and stage. Using Harrell's c-index to compare the scoring systems, qGS (0.83), swGS (0.84), and siGS (0.84) all performed better than the traditional Gleason score (0.82). CONCLUSIONS: Quantitative measures of Gleason pattern 4 predict BCR better than the traditional Gleason score. PATIENT SUMMARY: In men with Gleason 7 prostate cancer, quantitative analysis of the proportion of Gleason pattern 4 (quantitative Gleason score), as well as size-weighted measurement of Gleason 4 (size-weighted Gleason score), and a size-weighted measurement of Gleason 4 based on the largest tumor nodule significantly improve the predicted risk of biochemical recurrence compared with the traditional Gleason score.

INTRODUCTION: There is increasing interest in using imaging in the detection and localization of prostate cancer (PCa). Both multiparametric magnetic resonance imaging (mpMRI) and HistoScanning (HS) have been independently evaluated in the detection and localization of PCa. We undertook a prospective, blinded comparison of mpMRI and HS for cancer localization among men undergoing radical prostatectomy. METHODS: Following approval by the institutional review board, men scheduled to undergo radical prostatectomy, who had previously undergone mpMRI at our institution, were offered inclusion in the study. Those consenting underwent preoperative HS following induction of anesthesia; mpMRI, HS, and surgical step-section pathology were independently read by a single radiologist, urologist, and pathologist, respectively, in a blinded fashion. Disease maps created by each independent reader were compared and evaluated for concordance by a 5 persons committee consisting of 2 urologists, 2 pathologists, and 1 radiologist. Logistic regression for correlated data was used to assess and compare mpMRI and HS in terms of diagnostic accuracy for cancer detection. Generalized estimating equations based on binary logistic regression were used to model concordance between reader opinion and the reference standard assessment of the same lesion site or region as a function of imaging modality. RESULTS: Data from 31/35 men enrolled in the trial were deemed to be evaluable. On evaluation of cancer localization, HS identified cancer in 36/78 (46.2%) regions of interest, as compared with 41/78 (52.6%) on mpMRI (P = 0.3968). The overall accuracy, positive predictive value, negative predictive value, and specificity for detection of disease within a region of interest were significantly better with mpMRI as compared with HS. HS detected 36/84 (42.9%) cancer foci as compared with 42/84 (50%) detected by mpMRI (P = 0.3678). Among tumors with Gleason score>6, mpMRI detected 19/22 (86.4%) whereas HS detected only 11/22 (50%, P = 0.0078). Similarly, among tumors>10mm in maximal diameter, mpMRI detected 28/34 (82.4%) whereas HS detected only 19/34 (55.9%, P = 0.0352). CONCLUSION: In our institution, the diagnostic accuracy of HS was inferior to that of mpMRI in PCa for PCa detection and localization. Although our study warrants validation from larger cohorts, it would suggest that the HS protocol requires further refinement before clinical implementation.

BACKGROUND: To assess associations between whole-lesion apparent diffusion coefficient (ADC) metrics and pathologic findings of Likert score 3 prostate lesions at MRI/ultrasound fusion targeted biopsy. METHODS: This retrospective Institutional Review Board-approved study received a waiver of consent. We identified patients receiving a highest lesion score of 3 on 3 Tesla multiparametric MRI reviewed by a single experienced radiologist using a 5-point Likert scale and who underwent fusion biopsy. A total of 188 score 3 lesions in 158 patients were included. Three-dimensional volumes-of-interest encompassing each lesion were traced on ADC maps. Logistic regression was used to predict biopsy results based on whole-lesion ADC metrics and patient biopsy history. Biopsy yield was compared between metrics. RESULTS: By lesion, targeted biopsy identified tumor in 22.3% and Gleason score (GS) > 6 tumor in 8.5%, although results varied by biopsy history: biopsy-naive (n = 80), 20.0%/8.8%; prior negative biopsy (n = 53), 9.4%/1.9%; prior positive biopsy (n = 55): 40.0%/14.5%. Biopsy history, whole-lesion mean ADC, whole-lesion ADC10-25 , and whole-lesion ADC25-50 were each significantly associated with tumor or GS > 6 tumor at fusion biopsy (P 6 tumor, which was significantly higher (P < 0.001) than specificity of PSA (17.5%) at identical sensitivity. CONCLUSION: For score 3 lesions in patients without prior negative biopsy, whole-lesion ADC metrics help detect GS > 6 cancer while avoiding negative biopsies. However, deferral of fusion biopsy may be considered for score 3 lesions in patients with prior negative biopsy (without applying whole-lesion ADC metrics) given exceedingly low ( approximately 2%) frequency of GS > 6 tumor in this group. J. Magn. Reson. Imaging 2015.