Faculty Bibliography

The primary goal of a focal therapy treatment paradigm is to achieve cancer control through targeted tissue destruction while simultaneously limiting deleterious effects on peri-prostatic structures. Focal therapy approaches are employed in several oncologic treatment protocols, and have been shown to provide equivalent cancer control for malignancies such as breast cancer and renal cell carcinoma. Efforts to develop a focal therapy approach for prostate cancer have been challenged by several concepts including the multifocal nature of the disease and limited capability of prostate ultrasound and systematic biopsy to reliably localize the site(s) and aggressiveness of disease. Multi-parametric MRI (mpMRI) of the prostate has significantly improved disease localization, spatial demarcation and risk stratification of cancer detected within the prostate. The accuracy of this imaging modality has further enabled the urologist to improve biopsy approaches using targeted biopsy via MRI-ultrasound fusion. From this foundation, an improved delineation of the location of disease has become possible, providing a critical foundation to the development of a focal therapy strategy. This chapter reviews the accuracy of mpMRI for detection of "aggressive" disease, the accuracy of mpMRI in determining the tumor volume, and the ability of mpMRI to accurately identify the index lesion. While mpMRI provides a critical, first step in developing a strategy for focal therapy, considerable questions remain regarding the relationship between MR identified tumor volume and pathologic tumor volume, the accuracy and utility of mpMRI for treatment surveillance and the optimal role and timing of follow-up mpMRI.

OBJECTIVE: To explore and identify factors that influence physicians' decisions while monitoring patients with prostate cancer on active surveillance (AS). SUBJECTS AND METHODS: A purposive sampling strategy was used to identify physicians treating prostate cancer from diverse clinical backgrounds and geographic areas across the USA. We conducted 24 in-depth interviews from July to December 2015, until thematic saturation was reached. The Applied Thematic Analysis framework was used to guide data collection and analysis. Interview transcripts were reviewed and coded independently by two researchers. Matrix analysis and NVivo software were used for organization and further analysis. RESULTS: Eight key themes emerged to explain variation in AS monitoring: (i) physician comfort with AS; (ii) protocol selection; (iii) beliefs about the utility and quality of testing; (iv) years of experience and exposure to AS during training; (v) concerns about inflicting 'harm'; (vi) patient characteristics; (vii) patient preferences; and (viii) financial incentives. CONCLUSION: These qualitative data reveal which factors influence physicians who manage patients on AS. There is tension between providing standardized care while also considering individual patients' needs and health status. Additional education on AS is needed during urology training and continuing medical education. Future research is needed to empirically understand whether any specific protocol is superior to tailored, individualized care.

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.

Approximately 100,000 radical prostatectomies (RP) are performed annually in the US with the intent to cure clinically localized prostate cancer. Oncological control following RP is assessed by monitoring serum PSA levels. By consensus, a PSA exceeding 0.2 ng/mL is considered the threshold for a biochemical recurrence (BCR) following RP (3). BCR often predates radiographic and clinical evidence of disease recurrence by many years (4-6)

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.