Faculty Bibliography

CONTEXT: Focal therapy of prostate cancer has been proposed as an alternative to whole-gland treatments. OBJECTIVE: To summarize the evidence regarding sources of energy employed in focal therapy. EVIDENCE ACQUISITION: Embase and Medline (PubMed) were searched from 1996 to October 31, 2015 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Ongoing trials were selected from electronic registries. The stage of assessment of each source of energy was determined using the Idea, Development, Exploration, Assessment, Long-term study recommendations. EVIDENCE SYNTHESIS: Thirty-seven articles reporting on 3230 patients undergoing focal therapy were selected. Thirteen reported on high-intensity focused ultrasound, 11 on cryotherapy, three on photodynamic therapy, four on laser interstitial thermotherapy, two on brachytherapy, three on irreversible electroporation, and one on radiofrequency. High-intensity focused ultrasound, cryotherapy, photodynamic therapy, and brachytherapy have been assessed in up to Stage 2b studies. Laser interstitial thermotherapy and irreversible electroporation have been evaluated in up to Stage 2a studies. Radiofrequency has been evaluated in one Stage 1 study. Median follow-up varied between 4 mo and 61 mo, and the median rate of serious adverse events ranged between 0% and 10.6%. Pad-free leak-free continence and potency were obtained in 83.3-100% and 81.5-100%, respectively. In series with intention to treat, the median rate of significant and insignificant disease at control biopsy varied between 0% and 13.4% and 5.1% and 45.9%, respectively. The main limitations were the length of follow-up, the absence of a comparator arm, and study heterogeneity. CONCLUSIONS: Focal therapy has been evaluated using seven sources of energy in single-arm retrospective and prospective development studies up to Stage 2b. Focal therapy seems to have a minor impact on quality of life and genito-urinary function. Oncological effectiveness is yet to be defined against standard of care. PATIENT SUMMARY: Seven sources of energy have been employed to selectively ablate discrete areas of prostate cancer. There is high evidence that focal therapy is safe and has low detrimental impact on continence and potency. The oncological outcome has yet to be evaluated against standard of care.

PURPOSE: To compare image quality and diagnostic performance for detecting local recurrence (LR) of prostate cancer after radical prostatectomy (RP) between standard dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and a high spatiotemporal resolution, continuously acquired Golden-angle RAdial Sparse Parallel acquisition employing compressed sensing reconstruction ("GRASP"). METHODS: A search was conducted for prostate MRI examinations performed in patients with PSA >/=0.2 ng/mL after RP in whom follow-up evaluation allowed classification as positive (>/=50% PSA reduction after pelvic radiation or positive biopsy) or negative (<50% PSA reduction after pelvic radiation; spontaneous PSA normalization) for LR, yielding 13 patients with standard DCE (11 LR+) and 12 with GRASP (10 LR+). Standard DCE had voxel size 3.0 x 1.9 x 1.9 mm and temporal resolution 5.5 s. GRASP had voxel size 1.0 x 1.1 x 1.1 cm and was retrospectively reconstructed at 2.3 s resolution. Two radiologists evaluated DCE sequences for image quality measures (1-5 scale) and the presence of LR. RESULTS: GRASP achieved higher scores than standard DCE from both readers (p < 0.001-0.136) for anatomic clarity (R1: 4.4 +/- 0.8 vs. 2.8 +/- 0.67 R2: 4.8 +/- 0.5 vs. 3.2 +/- 0.6), sharpness (3.6 +/- 0.9 vs. 2.5 +/- 0.7; 4.6 +/- 0.5 vs. 2.6 +/- 0.5), confidence in interpretation (3.8 +/- 0.8 vs. 3.1 +/- 0.9; 3.8 +/- 1.0 vs. 3.1 +/- 1.2), and conspicuity of detected lesions (4.7 +/- 0.5 vs. 3.8 +/- 1.1; 4.5 +/- 0.5 vs. 3.8 +/- 1.0). For detecting LR, GRASP also achieved higher sensitivity (70% vs. 36%; 80% vs. 45%), specificity (R1 and R2: 100% vs. 50%), and accuracy (75% vs. 38%; 83% vs. 46%) for both readers. CONCLUSION: Although requiring larger studies, high spatiotemporal resolution GRASP achieved substantially better image quality and diagnostic performance than standard DCE for detecting LR in patients with elevated PSA after prostatectomy.

OBJECTIVES: To determine whether a combination of PCA3 and MRI suspicion score (mSS) could further optimize detection of prostate cancer on MRF-TB among men with no previous history of biopsy. MATERIALS AND METHODS: 187 men presenting to our institution between 6/12 and 8/14 who underwent multiparametric MRI and PCA3 prior to MRF-TB. Biopsy results, stratified by biopsy indication and PCA3 score, were recorded. Receiver operating characteristics (ROC) curves and multivariable logistic regressions were utilized to model the association of PCA3 and mSS with cancer detection on MRF-TB. RESULTS: PCA3 is associated with cancer detection on MRF-TB for men with no prior biopsies (AUC = 0.67, 95% CI 0.59-0.76). Using a cutoff of >/=35, PCA3 was associated with cancer risk among men with mSS 2-3 (p=0.004), but not among those with mSS 4-5 (p=0.340). The interaction of PCA3 and mSS demonstrated significantly higher discrimination for cancer than mSS alone (AUC: 0.83 vs. 0.79, p=0.0434). CONCLUSIONS: Urinary PCA3 is associated with mSS and the detection of cancer on MRF-TB for men with no prior biopsies. PCA3 notably demonstrates a high negative predictive value among mSS 2-3. However, in the case of high suspicion mpMRI, PCA3 is not associated with cancer detection on MRF-TB adding little to cancer diagnosis. Further studies are needed to evaluate the utility of PCA3 in predicting cancer among men with normal mpMRI.

BACKGROUND AND PURPOSE:Whereas open radical prostatectomy is performed extraperitoneally, minimally invasive radical prostatectomy is typically performed within the peritoneal cavity. Our objective was to determine whether minimally invasive radical prostatectomy is associated with an increased risk of small bowel obstruction compared with open radical prostatectomy. PATIENTS AND METHODS:In the U.S. Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified 14,147 men found to have prostate cancer from 2000 to 2008 treated by open (n = 10,954) or minimally invasive (n = 3193) radical prostatectomy. Multivariable Cox proportional hazard models were used to examine the impact of surgical approach on the diagnosis of small bowel obstruction, as well as the need for lysis of adhesions and exploratory laparotomy. RESULTS:During a median follow-up of 45 and 76 months, respectively, the cumulative incidence of small bowel obstruction was 3.7% for minimally invasive and 5.3% for open radical prostatectomy (p = 0.0005). Lysis of adhesions occurred in 1.1% of minimally invasive and 2.0% of open prostatectomy patients (p = 0.0003). On multivariable analysis, there was no significant difference between minimally invasive and open prostatectomy with respect to small bowel obstruction (HR 1.17, 95% CI 0.90, 1.52, p = 0.25) or lysis of adhesions (HR 0.87, 95% CI 0.50, 1.40, p = 0.57). Limitations of the study include the retrospective design and use of administrative claims data. CONCLUSIONS:Relative to open radical prostatectomy, minimally invasive radical prostatectomy is not associated with an increased risk of postoperative small bowel obstruction and lysis of adhesions.

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

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.

Over the last 2 decades the evolution of alpha-blockers for lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) has been to preserve effectiveness, improve tolerability, and eliminate dose titration. Today, alpha-blockers represent the first-line treatment of most men with BPH whereby the primary objective is relief from bothersome LUTS.

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.