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.

The surgical robot, a costly technology for treatment of prostate cancer with equivocal marginal benefit, rapidly diffused into clinical practice. We sought to evaluate the role of teaching in the early adoption phase of the surgical robot. Teaching hospitals were the primary early adopters: data from the Healthcare Cost and Utilization Project showed that surgical robots were acquired by 45.5% of major teaching, 18.0% of minor teaching and 8.0% of non-teaching hospitals during the early adoption phase. However, teaching hospital faculty produced little comparative effectiveness research: By 2008, only 24 published studies compared robotic prostatectomy outcomes to those of conventional techniques. Just ten of these studies (41.7%) were more than minimally powered, and only six (25%) involved cross-institutional collaborations. In adopting the surgical robot, teaching hospitals fulfilled their mission to innovate, but failed to generate corresponding scientific evidence.

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.

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.

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.

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.