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Background Intermediate clinical endpoints (ICEs) prognostic for overall survival (OS) are needed for men receiving postprostatectomy radiation therapy (PORT) to improve clinical trial design. Objective To identify a potential ICE for men receiving PORT. Design, setting, and participants We performed an institutional review board–approved multi-institutional retrospective study of 566 men consecutively treated with PORT at tertiary care centers from 1986 to 2013. The median follow-up was 8.2 yr. Outcome measurements and statistical analysis Biochemical failure (BF), distant metastases (DM), and castrate-resistant prostate cancer (CRPC) were evaluated for correlation with OS and assessed as time-dependent variables in a multivariable Cox proportional hazards model and in landmark analyses at 1, 3, 5, and 7 yr after PORT. Cross-validated concordance ( c ) indices were used to assess model discrimination. Results and limitations OS at 1, 3, 5, and 7 yr after PORT was 98%, 95%, 90%, and 82%, respectively. In a time-varying model controlling for clinical and pathologic variables, BF (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.45–3.71; p p p c index when adjusting for baseline covariates (0.78), with 5-yr DM also providing the greatest increase in discriminatory power over a model only including baseline covariates. These findings require validation in prospective randomized data. Conclusions While limited by the retrospective nature of the data, 5-yr DM is associated with lower OS following PORT, outperforming the prognostic capability of BF and CRPC at 1, 3, 5, or 7 yr after treatment. Confirmation of this ICE as a surrogate for OS is needed from randomized trial data so that it can be incorporated into future clinical trial design. Patient summary We assessed potential intermediate clinical endpoints prognostic for overall survival in a cohort of men receiving radiotherapy after prostatectomy. We identified the development of metastatic disease within 5 yr after treatment as the strongest predictor of overall survival.

Background Clinical registries provide physicians with a means for making data-driven decisions but few opportunities exist for patients to interact with registry data to help make decisions. Objective We sought to develop a web-based system that uses a prostate cancer (CaP) registry to provide newly diagnosed men with a platform to view predicted treatment decisions based on patients with similar characteristics. Design, setting, and participants The Michigan Urological Surgery Improvement Collaborative (MUSIC) is a quality improvement consortium of urology practices that maintains a prospective registry of men with CaP. We used registry data from 45 MUSIC urology practices from 2015 to 2017 to develop and validate a random forest machine learning model. After fitting the random forest model to a derivation cohort consisting of a random two-thirds sample of patients after stratifying by practice location, we evaluated the model performance in a validation cohort consisting of the remaining one-third of patients using a multiclass area under the curve (AUC) measure and calibration plots. Results and limitations We identified 7543 men diagnosed with CaP, of whom 45% underwent radical prostatectomy, 30% surveillance, 17% radiation therapy, 5.6% androgen deprivation, and 1.8% watchful waiting. The personalized prediction for patients in the validation cohort was highly accurate (AUC 0.81). Conclusions Using clinical registry data and machine learning methods, we created a web-based platform for patients that generates accurate predictions for most CaP treatments. Patient summary We have developed and tested a tool to help men newly diagnosed with prostate cancer to view predicted treatment decisions based on similar patients from our registry. We have made this tool available online for patients to use.

Active surveillance (AS) has emerged as the preferred management strategy for many men with prostate cancer (PC); however, insufficient longitudinal monitoring may increase the risk of poor outcomes. We sought to determine rates of patients becoming lost to follow-up (LTFU) and associated risk factors in a large AS cohort. The Michigan Urologic Surgery Improvement Collaborative (MUSIC) maintains a prospective registry of PC patients from 44 academic and community urology practices. Over a 6-yr period (2011-2017), we identified patients managed with AS. LTFU was defined as any 18-mo period where no pertinent surveillance testing was entered in the registry. With a median surveillance period of 32 mo, the estimated 2-yr LTFU-free probability calculated by Kaplan-Meier method was 90% (95% confidence interval [CI]=89-92%). Both African American race (hazard ratio [HR]: 2.77, 95% CI=1.81-4.24) and Charlson comorbidity index ≥1 (HR: 1.55, 95% CI=1.08-2.23) were independently associated with increased risk of LTFU. There was variability in rates of estimated 2-yr LTFU-free survival across MUSIC practices, ranging from 52% (95% CI=21-100%) to 99% (95% CI=97-100%), with a median of 96% (interquartile range: 94-98%), although this did not reach statistical significance (p=0.076). These data reveal opportunities for urology practices to identify systems to reduce rates of LTFU and improve the long-term safety of AS. PATIENT SUMMARY: With a median observation period of 32 mo, an estimated 10% of patients will be lost to follow-up at the 2 yr time point while on AS. African American men and generally unhealthy patients were at increased risk, and there was variability from one urology practice to another. There is ample opportunity to improve the quality of the performance of AS.

Active surveillance (AS) has been proposed as an effective strategy to reduce overtreatment among men with lower risk prostate cancers. However, historical rates of initial surveillance are low (4-20%), and little is known about its application among community-based urology practices.To describe contemporary utilization of AS among a population-based sample of men with low-risk prostate cancer.We performed a prospective cohort study of men with low-risk prostate cancer managed by urologists participating in the Michigan Urological Surgery Improvement Collaborative (MUSIC).The principal outcome was receipt of AS as initial management for low-risk prostate cancer including the frequency of follow-up prostate-specific antigen (PSA) testing, prostate biopsy, and local therapy. We examined variation in the use of surveillance according to patient characteristics and across MUSIC practices. Finally, we used claims data to validate treatment classification in the MUSIC registry.We identified 682 low-risk patients from 17 MUSIC practices. Overall, 49% of men underwent initial AS. Use of initial surveillance varied widely across practices (27-80%; p=0.005), even after accounting for differences in patient characteristics. Among men undergoing initial surveillance with at least 12 mo of follow-up, PSA testing was common (85%), whereas repeat biopsy was performed in only one-third of patients. There was excellent agreement between treatment assignments in the MUSIC registry and claims data (κ=0.93). Limitations include unknown treatment for 8% of men with low-risk cancer.Half of men in Michigan with low-risk prostate cancer receive initial AS. Because this proportion is much higher than reported previously, our findings suggest growing acceptance of this strategy for reducing overtreatment.We examined the use of initial active surveillance for the management of men with low-risk prostate cancer across the state of Michigan. We found that initial surveillance is used much more commonly than previously reported, but the likelihood of a patient being placed on surveillance depends strongly on where he is treated.

Background Intensity-modulated radiotherapy (IMRT) is increasingly used to treat localized prostate cancer. Although allowing for the delivery of higher doses of radiation to the prostate, its effectiveness compared with the prior standard three-dimensional conformal therapy (3D-CRT) is uncertain. Objective To examine the comparative effectiveness of IMRT relative to 3D-CRT. Design, setting, and participants We performed a population-based cohort study using Surveillance, Epidemiology, and End Results-Medicare data to identify men diagnosed with prostate cancer between 2001 and 2007 who underwent either 3D-CRT ( n =6976) or IMRT ( n =11 039). Outcome measurements and statistical analysis We assessed our main outcomes (ie, the adjusted use of salvage therapy with androgen-deprivation therapy [ADT] and risk of a complication requiring an intervention) using Cox proportional hazards models. Results and limitations The percentage of men receiving IMRT increased from 9% in 2001 to 93% in 2007. Compared with those treated with 3D-CRT, low-risk patients treated with IMRT had similar likelihoods of using salvage therapy with ADT and similar risks of having a complication requiring an intervention (all p >0.05). Conversely, a subset of higher risk patients treated with IMRT who did not receive concurrent ADT were less likely to use salvage therapy ( p =0.02) while maintaining similar complication rates. Because our cohort includes Medicare beneficiaries, our findings may not be generalizable to younger patients. Conclusions For a subset of higher risk patients, IMRT appears to show a benefit in terms of reduced salvage therapy without an increase in complications. For other patients, the risks of salvage therapy and complications are comparable between the two modalities.

Recent work from surgeons in Europe and the United States has provided both the motivation, and a blueprint, for implementing peer assessments of technical skill as a robust and practical strategy for evaluating and ultimately improving technical expertise with radical prostatectomy.

The potential harms of a prostate cancer (PCa) diagnosis may outweigh its benefits in elderly men.To assess the use of prostate biopsy in men with limited life expectancy (LE) within the practices comprising the Michigan Urological Surgery Improvement Collaborative (MUSIC).MUSIC is a consortium of 42 practices and nearly 85% of the urologists in Michigan. From July 2013 to October 2014, clinical data were collected prospectively for all men undergoing prostate biopsy.We calculated comorbidity-adjusted LE in men aged ≥66 yr and identified men with10 yr LE (limited LE) undergoing a first biopsy. Our LE calculator was not designed for men aged66 yr; thus these men were excluded. Multivariable models estimated the proportion of all biopsies performed for men with limited LE in each MUSIC practice, adjusting for differences in patient characteristics. We also evaluated what treatments, if any, these patients received.Among 3035 men aged ≥66 yr undergoing initial prostate biopsy, 60% had none of the measured comorbidities. Overall, 547 men (18%) had limited LE. Compared with men with a longer LE, these men had significantly higher prostate-specific antigen levels and abnormal digital rectal examination findings. The adjusted proportion of biopsies performed for men with limited LE ranged from 3.8% to 39% across MUSIC practices (p0.001). PCa was diagnosed in 69% of men with limited LE; among this group, 74% received any active treatment. Of these men, 46% had high-grade cancer (Gleason score 8-10).Among a large and diverse group of urology practices, nearly 20% of prostate biopsies are performed in men with limited LE. These data provide useful context for quality improvement efforts aimed at optimizing patient selection for prostate biopsy.In this report, nearly 2 of every 10 men undergoing prostate biopsy had a life expectancy (LE)10 yr. Implementing LE calculators in clinical practice may help refine patient selection for prostate biopsy.

Author(s): Gandaglia, Giorgio; Bray, Freddie; Cooperberg, Matthew R; Karnes, R Jeffrey; Leveridge, Michael J; Moretti, Kim; Murphy, Declan G; Penson, David F; Miller, David C