Faculty Bibliography

BACKGROUND:An increasing proportion of prostate cancer is being managed conservatively. However, there are no randomized trials or consensus regarding the optimal follow-up strategy. OBJECTIVE:To compare life expectancy and quality of life between watchful waiting (WW) versus different strategies of active surveillance (AS). DESIGN, SETTING, AND PARTICIPANTS/METHODS:A Markov model was created for US men starting at age 50, diagnosed with localized prostate cancer who chose conservative management by WW or AS using different testing protocols (prostate-specific antigen every 3-6 mo, biopsy every 1-5 yr, or magnetic resonance imaging based). Transition probabilities and utilities were obtained from the literature. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/UNASSIGNED:Primary outcomes were life years and quality-adjusted life years (QALYs). Secondary outcomes include radical treatment, metastasis, and prostate cancer death. RESULTS AND LIMITATIONS/CONCLUSIONS:All AS strategies yielded more life years compared with WW. Lifetime risks of prostate cancer death and metastasis were, respectively, 5.42% and 6.40% with AS versus 8.72% and 10.30% with WW. AS yielded more QALYs than WW except in cohorts age >65 yr at diagnosis, or when treatment-related complications were long term. The preferred follow-up strategy was also sensitive to whether people value short-term over long-term benefits (time preference). Depending on the AS protocol, 30-41% underwent radical treatment within 10 yr. Extending the surveillance biopsy interval from 1 to 5 yr reduced life years slightly, with a 0.26 difference in QALYs. CONCLUSIONS:AS extends life more than WW, particularly for men with higher-risk features, but this is partly offset by the decrement in quality of life since many men eventually receive treatment. PATIENT SUMMARY/UNASSIGNED:More intensive active surveillance protocols extend life more than watchful waiting, but this is partly offset by decrements in quality of life from subsequent treatment.

Objectives: Nocturia is a multifactorial condition with numerous comorbidities. The efficacy of SER120 after controlling for placebo effect was investigated in a subset of patients with nocturia due to nocturnal polyuria (NP) with concomitant overactive bladder (OAB) in two randomized, placebo-controlled trials. Methods: Two phase 3 trials enrolled patients >=50 years old who had experienced >=2 nocturia episodes for >=6 months. Patients were randomized 1:1:1 to SER120 1.66 mcg, 0.83 mcg or placebo for a 12-week treatment period after a 2-week placebo-controlled run-in period to control for placebo effect. Placebo responder patients (achieving 50% decrease in nocturic episodes/night from baseline or a mean < 1.8 nocturic episodes/night) during the run-in period were excluded from the analysis. Placebo non-responders (mITT population) with OAB and NP were pooled for analysis. The co-primary efficacy endpoints were mean change from baseline in nocturic episodes/night and percentage of patients with 50% reduction in nocturic episodes/night (responding patients). Secondary efficacy endpoints included change in time from bedtime to first nocturic episode and percent of nights >=1 nocturic episodes/night. Meaningful clinical improvement in health-related quality of life (HRQoL) was also assessed in one trial using a newly validated patient reported outcome (PRO) in-strument called Impact of Night-time Urination (INTU). Results: Study patients (n=207) with nocturia due to OAB and NP (mean age 68.3+/-9.9 years, 60.9% female, 78.3% Caucasian) showed significant results for both doses in both co-primary endpoints following treatment with SER120 compared to placebo. The reduction in mean nocturic episodes/night for the 1.66 mcg dose was 2 times that of placebo (-1.4 vs.-0.7, p=0.0010) and for the 0.83 mcg dose almost 2 times that of placebo (-1.3 vs.-0.7, p=0.0076). The percentage of responding patients for the 1.66 mcg dose was > 3 times greater than placebo (36.5% vs. 10.9%, p=0.0007) and for the 0.83 mcg dose was >2.5 times that of placebo (29% vs. 10.9%, p=0.0096). Secondary efficacy endpoints also showed significant results. Time from bedtime to first nocturic void showed an increase from baseline for SER120 of 72 minutes (1.66 mcg, p=0.0136) and 84 minutes (0.83 mcg, p=0.0036) vs 30 minutes for placebo. The percentage of nights with >=1 episode/night showed an increase from baseline for SER120 of 28.18% (1.66 mcg, p=0.0161) and 26.86% (0.83 mcg, p=0.0269) vs. 11.79% for placebo. The PRO instrument also showed significant improvements on HRQoL for both SER120 doses compared to placebo. The reduction in total impact score was-12.1 (1.66 mcg, p=0.0056),-10.4 (0.83 mcg, p=0.0244) and-2.1 (placebo). Two patients at the 1.66 mcg dose who were on systemic steroids had serum sodium >=125 mmol/L. No patients at the 0.83 mcg dose had serum sodium >=125 mmol/L. Conclusions: SER120 at doses of 1.66 and 0.83 mcg is effective for the treatment of patients with nocturia due to NP with concomitant OAB. The results of the PRO (INTU) instrument demonstrated that SER120 has a clinical meaningful benefit and statistically significant improvement on HRQoL. SER120 was shown to be safe and well tolerated in this patient population

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)