Faculty Bibliography

Benign prostatic obstruction (BPO) contributes to the genesis of lower urinary tract symptoms as well as to pathologic remodeling of the lower and upper urinary tract in patients with benign prostate enlargement. Urodynamic studies demonstrate that both medical therapy with alpha-blockers (ABs) and endoscopic surgical procedures provide BPO relief. However, the magnitude of improvement is higher after surgery. Among ABs, silodosin is associated with the highest improvement of bladder outlet obstruction index (BOOI). A complex relationship exists between BOOI improvement and variations of both maximum urinary flow (Q max) and detrusor pressure. When the reduction of BOOI is small, the improvement of Q max is clinically irrelevant and the BOOI is mainly influenced by a decrease of detrusor pressure. In contrast, when the magnitude of BOOI reduction is robust, a meaningful improvement of both detrusor pressure and urinary flow is evident. When clustering ABs according to their receptor pharmacologic selectivity and urodynamic efficacy, three subgroups can be identified,with silodosin being the only member of a subgroup characterized by the highest levels of BOOI improvement and alpha-1A/alpha-1B receptor affinity ratio.

OBJECTIVE: To determine how ipsilateral (ipsi) and contralateral (contra) systematic biopsies (SB) impacts detection of clinically significant versus insignificant prostate cancer (PCa) in men with unilateral MRI lesion undergoing MRI fusion target biopsy (MRF-TB). MATERIALS AND METHODS: 211 cases with one unilateral MRI lesion were subjected to SB and MRF-TB. Biopsy tissue cores from the MRF-TB, ipsi-SB and contra-SB were analyzed separately. RESULTS: A direct relationship was observed between MRI suspicious score (SS) and detection of any cancer, Gleason 6 PCa and Gleason > 6 PCa. MRF-TB alone, MRF-TB + ipsi-SB and MRF-TB + contra-SB detected 64.1%, 89.1% and 76.1% of all PCa, respectively, 53.5%, 81.4% and 69.8% of Gleason 6 PCa, respectively, and 73.5%, 96.0% and 81.6% of Gleason >6 PCa, respectively. MRF-TB + ipsi-SB detected 96% of clinically significant PCa and avoided detection of 18.6% of clinically insignificant PCa. MRF-TB + contra-SB detected 81.6% of clinically significant PCa and avoided detection of 30.2% of clinically insignificant PCa. CONCLUSION: Our study suggests that ipsi-SB should be added to MRF-TB as detection of clinically significant PCa increases with only a modest increase in clinically insignificant PCa detection. Contra-SB in this setting may be deferred since it primarily detects clinically insignificant PCa.

PURPOSE: NRG Oncology RTOG 9202 was a randomized trial testing long-term adjuvant androgen deprivation (LTAD) versus initial androgen deprivation only (STAD) with external beam radiation therapy (RT) in mostly high-risk and some intermediate-risk prostate cancer patients. RTOG 9408 found an overall survival (OS) advantage in patients with cT1b-T2b disease and prostate-specific antigen (PSA) <20 ng/mL, with benefit observed mostly among intermediate-risk patients. It was still unknown whether intermediate-risk patients would experience an additional survival benefit with LTAD; thus, we performed a secondary analysis to explore whether LTAD had any incremental benefit beyond STAD among the intermediate-risk subset of RTOG 9202. The study endpoints were OS, disease-specific survival (DSS), and PSA failure (PSAF). METHODS AND MATERIALS: An analysis was performed for all patients enrolled in RTOG 9202 defined as intermediate-risk (cT2 disease, PSA<10 ng/mL, and Gleason score = 7 or cT2 disease, PSA 10-20 ng/mL, and Gleason score <7). This review yielded 133 patients: 74 (STAD) and 59 (LTAD). The Kaplan-Meier method was used to estimate OS; the cumulative incidence approach was used to estimate DSS and PSAF. A 2-sided test was used, with significance level defined to be .05. RESULTS: With over 11 years of median follow-up, 39 STAD patients were alive and 33 LTAD patients were alive. There was no difference in OS (10-year estimates, 61% STAD vs 65% LTAD; P=.53), DSS (10-year DSS, 96% vs 97%; P=.72), or PSAF (10-year PSAF, 53% vs 55%; P=.99) between groups. CONCLUSION: LTAD did not confer a benefit in terms of OS, DSS, or PSAF rates in the intermediate-risk subset in this study. Whereas the subset was relatively small, treatment assignment was randomly applied, and a trend in favor of LTAD would have been of interest. Given the small number of disease-specific deaths observed and lack of benefit with respect to our endpoints, this secondary analysis does not suggest that exploration of longer hormonal therapy is worth testing in the intermediate-risk prostate cancer subset.

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.

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.

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.