Faculty Bibliography

IMPORTANCE: Soy consumption has been suggested to reduce risk or recurrence of prostate cancer, but this has not been tested in a randomized trial with prostate cancer as the end point. OBJECTIVE: To determine whether daily consumption of a soy protein isolate supplement for 2 years reduces the rate of biochemical recurrence of prostate cancer after radical prostatectomy or delays such recurrence. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind trial conducted from July 1997 to May 2010 at 7 US centers comparing daily consumption of a soy protein supplement vs placebo in 177 men at high risk of recurrence after radical prostatectomy for prostate cancer. Supplement intervention was started within 4 months after surgery and continued for up to 2 years, with prostate-specific antigen (PSA) measurements made at 2-month intervals in the first year and every 3 months thereafter. INTERVENTION: Participants were randomized to receive a daily serving of a beverage powder containing 20 g of protein in the form of either soy protein isolate (n=87) or, as placebo, calcium caseinate (n=90). MAIN OUTCOMES AND MEASURES: Biochemical recurrence rate of prostate cancer (defined as development of a PSA level of >/=0.07 ng/mL) over the first 2 years following randomization and time to recurrence. RESULTS: The trial was stopped early for lack of treatment effects at a planned interim analysis with 81 evaluable participants in the intervention group and 78 in the placebo group. Overall, 28.3% of participants developed biochemical recurrence within 2 years of entering the trial (close to the a priori predicted recurrence rate of 30%). Among these, 22 (27.2%) occurred in the intervention group and 23 (29.5%) in the placebo group. The resulting hazard ratio for active treatment was 0.96 (95% CI, 0.53-1.72; log-rank P = .89). Adherence was greater than 90% and there were no apparent adverse events related to supplementation. CONCLUSION AND RELEVANCE: Daily consumption of a beverage powder supplement containing soy protein isolate for 2 years following radical prostatectomy did not reduce biochemical recurrence of prostate cancer in men at high risk of PSA failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00765479.

OBJECTIVE: To study the histopathology changes and clinical features of vesical diverticula, focusing on the neoplastic entities. MATERIALS AND METHODS: We retrieved data for 108 patients with vesical diverticula from the archives of our institute during the past 15 years (1998 to 2012) and reviewed their clinical and pathologic characteristics. RESULTS: Diverticula most often involved the lateral wall, followed by the posterolateral and posterior walls of the urinary bladder. Nonneoplastic processes were found in 70 of 108 patients (65%), including inflammation, metaplasia, and urothelial hyperplasia, with or without atypia/dysplasia. Primary carcinomas arising within the diverticula were found in 36 patients (33.3%), of which 33 were urothelial carcinoma, including 5 with divergent differentiation, 2 with squamous carcinoma, and 1 with adenocarcinoma. Patient follow-up for neoplastic diverticula (mean, 59 months; range, 1-108 months) showed that no patients died of disease progression. Concurrent or subsequent urothelial carcinoma was present in the nondiverticular bladder in 19 of 36 patients (53%). Four patients with subsequent extradiverticular urothelial carcinoma showed progression, with pathology upstaging. CONCLUSION: Inflammation, metaplasia, and dysplasia are commonly seen in vesical diverticula. In our series, which includes patients who underwent endoscopic or surgical intervention and microscopic examination, those with vesical diverticula appeared to have a significantly higher risk for development of urothelial carcinoma, which can occur synchronously or precede carcinoma of the nondiverticular bladder. Compared with their non-diverticulum-associated counterparts, a significantly higher percentage of diverticulum-associated bladder carcinomas are high-grade and invasive. Conservative approaches are suggested for tumors confined within diverticula, after extensive investigation of the nondiverticular bladder.

PURPOSE: An optimal prostate biopsy in clinical practice is based on a balance among adequate detection of clinically significant prostate cancers (sensitivity), assuredness regarding the accuracy of negative sampling (negative predictive value), limited detection of clinically insignificant cancers and good concordance with whole gland surgical pathology results to allow accurate risk stratification and disease localization for treatment selection. Inherent within this optimization is variation of the core number, location, labeling and processing for pathological evaluation. To date, there is no consensus in this regard. The purpose of this review is to 1) define the optimal number and location of biopsy cores during primary prostate biopsy among men with suspected prostate cancer, 2) define the optimal method of labeling prostate biopsy cores for pathological processing which will provide relevant and necessary clinical information for all potential clinical scenarios, and 3) determine the maximal number of prostate biopsy cores allowable within a specimen jar which would not preclude accurate histological evaluation of the tissue. MATERIALS AND METHODS: A bibliographic search using PubMed(R) covering the period up to July 2012 yielded approximately 550 articles. Articles were reviewed and categorized based on which of the 3 objectives of this review was addressed. Data were extracted, analyzed and summarized. Recommendations are provided based on this literature review and our clinical experience. RESULTS: The use of 10 to 12-core extended sampling protocols increases cancer detection rates compared to traditional sextant sampling methods and reduces the likelihood of repeat biopsy by increasing negative predictive value, ultimately allowing more accurate risk stratification without increasing the likelihood of detecting insignificant cancers. As the number of cores increases above 12, the increase in diagnostic yield becomes marginal. Only limited evidence supports the use of initial biopsy schemes involving more than 12 cores or saturation. Apical and laterally directed sampling of the peripheral zone increases cancer detection rate, reduces the need for repeat biopsies and predicts pathological features on prostatectomy while transition zone biopsies do not. There are little data to suggest that knowing the exact site of an individual positive biopsy core provides meaningful clinical information. However, determining laterality of cancer on biopsy may be helpful for predicting sites of extracapsular extension and therapeutic planning. Placement of multiple biopsy cores in a single container (greater than 2) appears to compromise pathological evaluation, which can reduce cancer detection rate and increase the likelihood of equivocal diagnoses. CONCLUSIONS: A 12-core systematic biopsy that incorporates apical and far-lateral cores in the template distribution allows maximal cancer detection, avoids repeat biopsy, and provides information adequate for identifying men who need therapy and planning that therapy while minimizing the detection of occult, indolent prostate cancers. This literature review does not provide compelling evidence that individual site specific labeling of cores benefits clinical decision making regarding the management of prostate cancer. Based on the available literature, we recommend packaging no more than 2 cores in each jar to avoid reduction of the cancer detection rate through inadequate tissue sampling.

OBJECTIVE: To determine whether suspicion for tumor on prostate MRI incorporating T2-weighted imaging (T2-WI) and diffusion-weighted imaging (DWI) predicts more adverse pathology on radical prostatectomy (RP). METHODS: From 2007 to 2009, 154 patients underwent 1.5 Tesla pelvic-phased-array magnetic resonance imaging (MRI) of the prostate that included T2-WI and DWI before RP. MRI examinations were retrospectively reviewed and grouped by degree of suspicion for tumor: no suspicion for tumor (NST, n = 15), equivocal suspicion for tumor (EST, n = 60), or strong suspicion for tumor (SST, n = 79). The NST/EST groups were combined and compared to the SST group. Preoperative variables were used to assemble a multivariate model. Outcomes reflective of adverse pathology included primary Gleason grade >/=4, pathologic stage >/=T3 (>/=pT3), and tumor upgrading. Subgroup analysis was performed for patients meeting eligibility criteria for active surveillance (n = 55). For this analysis, the NST group was compared to the EST/SST groups. RESULTS: SST status was associated with adverse preoperative risk factors for aggressive disease. Univariate analysis demonstrated significant association between SST and primary Gleason >/=4 pathology and stage >/=pT3 (P <.05). On multivariate analysis, SST was independently predictive of primary Gleason >/=4 pathology (odds ratio [OR] 6.14, 95% confidence interval [CI] 1.97-19.2) and Gleason upgrading (OR 2.47, 95% CI 1.01-6.02). Among patients eligible for active surveillance, those in the NST group had decreased likelihood of Gleason >/=7 disease or stage >/=pT3 compared to the EST/SST groups (7.7% vs 47.6%, P = .01). CONCLUSION: Increased tumor suspicion on T2-WI/DWI MRI is indicative of adverse pathology on RP. These findings suggest a role for MRI in pretreatment risk assessment.