Development of a Longitudinal Prostate Cancer Transcriptomic and Clinical Data Linkage.

Importance: Although tissue-based gene expression testing has become widely used for prostate cancer risk stratification, its prognostic performance in the setting of clinical care is not well understood. Objective: To develop a linkage between a prostate genomic classifier (GC) and clinical data across payers and sites of care in the US. Design, Setting, and Participants: In this cohort study, clinical and transcriptomic data from clinical use of a prostate GC between 2016 and 2022 were linked with data aggregated from insurance claims, pharmacy records, and electronic health record (EHR) data. Participants were anonymously linked between datasets by deterministic methods through a deidentification engine using encrypted tokens. Algorithms were developed and refined for identifying prostate cancer diagnoses, treatment timing, and clinical outcomes using diagnosis codes, Common Procedural Terminology codes, pharmacy codes, Systematized Medical Nomenclature for Medicine clinical terms, and unstructured text in the EHR. Data analysis was performed from January 2023 to January 2024. Exposure: Diagnosis of prostate cancer. Main Outcomes and Measures: The primary outcomes were biochemical recurrence and development of prostate cancer metastases after diagnosis or radical prostatectomy (RP). The sensitivity of the linkage and identification algorithms for clinical and administrative data were calculated relative to clinical and pathological information obtained during the GC testing process as the reference standard. Results: A total of 92 976 of 95 578 (97.2%) participants who underwent prostate GC testing were successfully linked to administrative and clinical data, including 53 871 who underwent biopsy testing and 39 105 who underwent RP testing. The median (IQR) age at GC testing was 66.4 (61.0-71.0) years. The sensitivity of the EHR linkage data for prostate cancer diagnoses was 85.0% (95% CI, 84.7%-85.2%), including 80.8% (95% CI, 80.4%-81.1%) for biopsy-tested participants and 90.8% (95% CI, 90.5%-91.0%) for RP-tested participants. Year of treatment was concordant in 97.9% (95% CI, 97.7%-98.1%) of those undergoing GC testing at RP, and 86.0% (95% CI, 85.6%-86.4%) among participants undergoing biopsy testing. The sensitivity of the linkage was 48.6% (95% CI, 48.1%-49.1%) for identifying RP and 50.1% (95% CI, 49.7%-50.5%) for identifying prostate biopsy. Conclusions and Relevance: This study established a national-scale linkage of transcriptomic and longitudinal clinical data yielding high accuracy for identifying key clinical junctures, including diagnosis, treatment, and early cancer outcome. This resource can be leveraged to enhance understandings of disease biology, patterns of care, and treatment effectiveness.

Proposal for an optimised definition of adverse pathology (unfavourable histology) that predicts metastatic risk in prostatic adenocarcinoma independent of grade group and pathological stage.

AIMS: Histological grading of prostate cancer is a powerful prognostic tool, but current criteria for grade assignment are not fully optimised. Our goal was to develop and test a simplified histological grading model, based heavily on large cribriform/intraductal carcinoma, with optimised sensitivity for predicting metastatic potential. METHODS AND RESULTS: Two separate non-overlapping cohorts were identified: a 419-patient post-radical prostatectomy cohort with long term clinical follow-up and a 209-patient post-radical prostatectomy cohort in which all patients had pathologically confirmed metastatic disease. All prostatectomies were re-reviewed for high-risk histological patterns of carcinoma termed 'unfavourable histology'. Unfavourable histology is defined by any classic Gleason pattern 5 component, any large cribriform morphology (> 0.25 mm) or intraductal carcinoma, complex intraluminal papillary architecture, grade 3 stromogenic carcinoma and complex anastomosing cord-like growth. For the outcome cohort, Kaplan-Meier analysis compared biochemical recurrence, metastasis and death between subjects with favourable and unfavourable histology, stratified by pathological stage and grade group. Multivariable Cox proportional hazards models evaluated adding unfavourable histology to the Memorial Sloan Kettering Cancer Center (MSKCC) post-prostatectomy nomogram and stratification by percentage of unfavourable histology. At 15 years unfavourable histology predicted biochemical recurrence, with sensitivity of 93% and specificity of 88%, metastatic disease at 100 and 48% and death at 100 and 46%. Grade group 2 prostate cancers with unfavourable histology were associated with metastasis independent of pathological stage, while those without had no risk. Histological models for prediction of metastasis based on only large cribriform/intraductal carcinoma or increasing diameter of cribriform size improved specificity, but with lower sensitivity. Multivariable Cox proportional hazards models demonstrated that unfavourable histology significantly improved discriminatory power of the MSKCC post-prostatectomy nomogram for biochemical failure (likelihood ratio test P < 0.001). In the retrospective review of a separate RP cohort in which all patients had confirmed metastatic disease, none had unequivocal favourable histology. CONCLUSIONS: Unfavourable histology at radical prostatectomy is associated with metastatic risk, predicted adverse outcomes better than current grading and staging systems and improved the MSKCC post-prostatectomy nomogram. Most importantly, unfavourable histology stratified grade group 2 prostate cancers into those with and without metastatic potential, independent of stage. While unfavourable histology is driven predominantly by large cribriform/intraductal carcinoma, the recognition and inclusion of other specific architectural patterns add to the sensitivity for predicting metastatic disease. Moreover, a simplified dichotomous model improves communication and could increase implementation.

Long-Term Outcomes in Patients Using Protocol-Directed Active Surveillance for Prostate Cancer.

Importance: Outcomes from protocol-directed active surveillance for favorable-risk prostate cancers are needed to support decision-making. Objective: To characterize the long-term oncological outcomes of patients receiving active surveillance in a multicenter, protocol-directed cohort. Design, Setting, and Participants: The Canary Prostate Active Surveillance Study (PASS) is a prospective cohort study initiated in 2008. A cohort of 2155 men with favorable-risk prostate cancer and no prior treatment were enrolled at 10 North American centers through August 2022. Exposure: Active surveillance for prostate cancer. Main Outcomes and Measures: Cumulative incidence of biopsy grade reclassification, treatment, metastasis, prostate cancer mortality, overall mortality, and recurrence after treatment in patients treated after the first or subsequent surveillance biopsies. Results: Among 2155 patients with localized prostate cancer, the median follow-up was 7.2 years, median age was 63 years, 83% were White, 7% were Black, 90% were diagnosed with grade group 1 cancer, and median prostate-specific antigen (PSA) was 5.2 ng/mL. Ten years after diagnosis, the incidence of biopsy grade reclassification and treatment were 43% (95% CI, 40%-45%) and 49% (95% CI, 47%-52%), respectively. There were 425 and 396 patients treated after confirmatory or subsequent surveillance biopsies (median of 1.5 and 4.6 years after diagnosis, respectively) and the 5-year rates of recurrence were 11% (95% CI, 7%-15%) and 8% (95% CI, 5%-11%), respectively. Progression to metastatic cancer occurred in 21 participants and there were 3 prostate cancer-related deaths. The estimated rates of metastasis or prostate cancer-specific mortality at 10 years after diagnosis were 1.4% (95% CI, 0.7%-2%) and 0.1% (95% CI, 0%-0.4%), respectively; overall mortality in the same time period was 5.1% (95% CI, 3.8%-6.4%). Conclusions and Relevance: In this study, 10 years after diagnosis, 49% of men remained free of progression or treatment, less than 2% developed metastatic disease, and less than 1% died of their disease. Later progression and treatment during surveillance were not associated with worse outcomes. These results demonstrate active surveillance as an effective management strategy for patients diagnosed with favorable-risk prostate cancer.

Patterns of Care for Medicare Beneficiaries With Metastatic Prostate Cancer.

INTRODUCTION: Therapeutic options for men with metastatic prostate cancer have increased in the past decade. We studied recent treatment patterns for men with metastatic prostate cancer and how treatment patterns have changed over time. METHODS: Using the Surveillance, Epidemiology, and End Results‒Medicare database, we identified fee-for-service Medicare beneficiaries who either were diagnosed with metastatic prostate cancer or developed metastases following diagnosis, as indicated by the presence of claims with diagnoses codes for metastatic disease, between 2007 and 2017. We evaluated treatment patterns using claims. RESULTS: We identified 29,800 men with metastatic disease, of whom 4721 (18.8%) had metastatic disease at their initial diagnosis. The mean age was 77 years, and 77.9% of patients were non-Hispanic White. The proportion receiving antineoplastic agents within 3 years of the index date increased over time (from 9.7% in 2007 to 25.9% in 2017; P < .001). Opioid use within 3 years of prostate cancer diagnosis was stable during 2007 to 2013 (around 73%) but decreased through 2017 to 65.5% (P < .001). Patients diagnosed during 2015 to 2017 had longer median survival (32.6 months) compared to those diagnosed during 2007 to 2010 (26.6 months; P < .001). CONCLUSIONS: Most metastatic prostate cancer patients do not receive life-prolonging antineoplastic therapies. Improved adoption of effective cancer therapies when appropriate may increase length and quality of survival among metastatic prostate cancer patients.

Disparities in time to prostate cancer treatment initiation before and after the Affordable Care Act.

BACKGROUND: Delayed access to care may contribute to disparities in prostate cancer (PCa). The Affordable Care Act (ACA) aimed at increasing access and reducing healthcare disparities, but its impact on timely treatment initiation for PCa men is unknown. METHODS: Men with intermediate- and high-risk PCa diagnosed 2010-2016 and treated with curative surgery or radiotherapy were identified in the National Cancer Database. Multivariable logistic regression modeled the effect of race and insurance type on treatment delay >180 days after diagnosis. Cochran-Armitage test measured annual trends in delays, and joinpoint regression assessed if 2014, the year the ACA became fully operationalized, was significant for inflection in crude rates of major delays. RESULTS: Of 422,506 eligible men, 18,720 (4.4%) experienced >180-day delay in treatment initiation. Compared to White patients, Black (OR 1.79, 95% CI 1.72-1.87, p < 0.001) and Hispanic (OR 1.37, 95% CI 1.28-1.48, p < 0.001) patients had higher odds of delay. Compared to uninsured, those with Medicaid had no difference in odds of delay (OR 0.94, 95% CI 0.84-1.06, p = 0.31), while those with private insurance (OR 0.57, 95% CI 0.52-0.63, p < 0.001) or Medicare (OR 0.64, 95% CI 0.58-0.70, p < 0.001) had lower odds of delay. Mean time to treatment significantly increased from 2010 to 2016 across all racial/ethnic groups (trend p < 0.001); 2014 was associated with a significant inflection for increase in rates of major delays. CONCLUSIONS: Non-White and Medicaid-insured men with localized PCa are at risk of treatment delays in the United States. Treatment delays have been consistently rising, particularly after implementation of the ACA.

The cost burden of metastatic prostate cancer in the US populations covered by employer-sponsored health insurance.

BACKGROUND: Recent advancements in the clinical management of metastatic prostate cancer include several costly therapies and diagnostic tests. The objective of this study was to provide updated information on the cost to payers attributable to metastatic prostate cancer among men aged 18 to 64 years with employer-sponsored health plans and men aged 18 years or older covered by employer-sponsored Medicare supplement insurance. METHODS: By using Merative MarketScan commercial and Medicare supplemental data for 2009-2019, the authors calculated differences in spending between men with metastatic prostate cancer and their matched, prostate cancer-free controls, adjusting for age, enrollment length, comorbidities, and inflation to 2019 US dollars. RESULTS: The authors compared 9011 patients who had metastatic prostate cancer and were covered by commercial insurance plans with a group of 44,934 matched controls and also compared 17,899 patients who had metastatic prostate cancer and were covered by employer-sponsored Medicare supplement plans with a group of 87,884 matched controls. The mean age of patients with metastatic prostate cancer was 58.5 years in the commercial samples and 77.8 years in the Medicare supplement samples. Annual spending attributable to metastatic prostate cancer was $55,949 per person-year (95% confidence interval [CI], $54,074-$57,825 per person-year) in the commercial population and $43,682 per person-year (95% CI, $42,022-$45,342 per person-year) in the population covered by Medicare supplement plans, both in 2019 US dollars. CONCLUSIONS: The cost burden attributable to metastatic prostate cancer exceeds $55,000 per person-year among men with employer-sponsored health insurance and $43,000 among those covered by employer-sponsored Medicare supplement plans. These estimates can improve the precision of value assessments of clinical and policy approaches to the prevention, screening, and treatment of prostate cancer in the United States.

Patterns of multispecialty care for low- and intermediate-risk prostate cancer in the use of active surveillance.

BACKGROUND: Multidisciplinary models of care have been advocated for prostate cancer (PC) to promote shared decision-making and facilitate quality care. Yet, how this model applies to low-risk disease where the preferred management is expectant remains unclear. Accordingly, we examined recent practice patterns in specialty visits for low/intermediate-risk PC and resultant use of active surveillance (AS). METHODS: Using SEER-Medicare, we ascertained whether patients saw urology and radiation oncology (i.e., multispecialty care) versus urology alone, based on self-designated specialty codes, for newly diagnosed PC from 2010 to 2017. We also examined the association with AS, defined as the absence of treatment within 12 months of diagnosis. Time trends were analyzed using Cochran-Armitage test. Chi-squared and logistic regression analyses were applied to compare sociodemographic and clinicopathologic characteristics between these models of care. RESULTS: The proportion of patients seeing both specialists was 35.5% and 46.5% for low- and intermediate-risk patients respectively. Trend analysis showed a decline in multispecialty care in low-risk patients (44.1% to 25.3% years 2010-2017; P < 0.001). Between 2010 and 2017, the use of AS increased 40.9% to 68.6% (P < 0.001) and 13.1% to 24.6% (P < 0.001) for patients seeing urology and those seeing both specialists respectively. Age, urban residence, higher education, SEER region, co-morbidities, frailty, Gleason score, predicted receipt of multispecialty care (all P < 0.02). CONCLUSIONS: Uptake of AS among men with low-risk PC has occurred primarily under the purview of urologists. While selection is certainly at play, these data suggest that multispecialty care may not be required to promote the utilization of AS for men with low-risk PC.

Use of expectant management based on prostate cancer risk and health status: How far are we from a risk-adapted approach?

OBJECTIVES: While active surveillance, a form of expectant management (EM), is preferred for patients with low-risk prostate cancer (PCa), some favor a more risk-adapted approach that recognizes patient preferences and condition-specific factors. However, previous research has shown non-patient-related factors often drive PCa treatment. In this context, we characterized trends in AS with respect to disease risk and health status. METHODS AND MATERIALS: Using SEER-Medicare data, we identified men 66 years and older diagnosed with localized low- and intermediate-risk PCa from 2008 to 2017 and examined receipt of EM, defined as the absence of treatment (i.e., surgery, cryotherapy, radiation, chemotherapy, and androgen deprivation therapies) within 1 year of diagnosis. We performed bivariable analysis to compare trends in use for EM vs. treatment, stratified by disease risk (i.e., Gleason 3+3, 3+4, 4+3; PSA<10, 10-20) and health status (i.e., NCI Comorbidity Index (NCI), frailty, life expectancy). We then ran a multivariable logistic regression model to examine determinants of EM. RESULTS: Within this cohort, 26,364 (38%) were categorized as low-risk (i.e., Gleason 3+3 and PSA<10) and 43,520 (62%) as intermediate-risk (i.e., all others). Over the study period, use of EM significantly increased across all risk groups, except for Gleason 4+3 (P = 0.662), as well across all health status groups. However, linear trends did not differ significantly between frail vs. nonfrail patients for both those categorized as low-risk (P = 0.446) and intermediate-risk (P = 0.208). Trends also did not differ between NCI 0 vs. 1 vs. >1 for low-risk PCa (P = 0.395). In the multivariable models, EM was associated with increasing age and being frail for men with both low- and intermediate risk disease. Conversely, EM selection was negatively associated with higher comorbidity score. CONCLUSIONS: EM increased significantly over time for patients with low- and favorable intermediate-risk disease, with the most notable differences based on age and Gleason score. In contrast, trends in uptake of EM did not differ substantively by health status, suggesting that physicians may not be effectively incorporating patient health into PCa treatment decisions. Additional work is needed to develop interventions that recognize health status as an essential component of a risk-adapted approach.

Characteristics of prostate cancer patients captured by facility-based versus geography-based cancer registries.

PURPOSE: We determined differences in demographics, tumor factors, and treatment patterns of prostate cancer patients in a geographic-based cancer registry based on eligibility for a facility-based cancer registry system. METHODS: We identified prostate cancer patients captured by the Surveillance, Epidemiology, and End Results (SEER) database from 2018 to 2019. Our exposure was receipt of cancer care at a facility accredited by the American College of Surgeons' Commission on Cancer (CoC) providing eligibility for inclusion in the National Cancer Database (NCDB). Outcomes included patient demographics, tumor factors (e.g., biopsy grade), and treatment with radical prostatectomy. RESULTS: We identified 113,733 prostate cancer patients of whom 65,708 (57%) were NCDB-eligible with an analytic abstract, and 11,010 (10%) were NCDB-eligible without an analytic abstract. NCDB-eligible men were younger (67.0 vs. 68.1 years, P < 0.001), less likely to be Hispanic/Latino (8.7% vs. 13.2%, P < 0.001), and more likely in a county with median income over $75,000 (40.9% vs. 30.0%, P < 0.001). NCDB eligibility varied widely by registry, from 95.9% in Connecticut to 42.6% in Utah. NCDB-ineligible patients were more likely to have unknown stage (17.2% vs. 2.9% NCDB-eligible) and missing PSA (22.9% vs 9.3% NCDB-eligible). NCDB-eligible men were less likely to have Grade Group 1 cancer on biopsy (28.2% vs. 39.2%, P < 0.001). Treatment with prostatectomy was more common among NCDB-eligible patients for low-risk (19.6% vs. 8.8%, adjusted OR 2.30, 95% CI 1.72-6.66) and high-risk tumors (43.5% vs. 26.0%, adjusted OR 1.95, 95% CI 1.33-2.86). CONCLUSION: Compared NCDB-ineligible patients, those eligible for inclusion in the NCDB have important differences in demographics, eligibility for active surveillance, and treatment patterns. Generalizations related to epidemiologic trends, practice patterns, and outcomes for this select population should be interpreted with caution.

The Cost of Metastatic Prostate Cancer in the United States.

INTRODUCTION: We sought to estimate per patient and annual aggregate health care costs related to metastatic prostate cancer. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified fee-for-service Medicare beneficiaries ages 66 and older diagnosed with metastatic prostate cancer or claims with diagnosis codes for metastatic disease (indicating tumor progression following diagnosis) between 2007 and 2017. We measured annual health care costs and compared costs between cases and a sample of beneficiaries without prostate cancer. RESULTS: We estimate that per-patient annual costs attributable to metastatic prostate cancer are $31,427 (95% CI: $31,219-$31,635; 2019 dollars). Annual attributable costs rose over time, from $28,311 (95% CI: $28,047-$28,575) in 2007-2013 to $37,055 (95% CI: $36,716-$37,394) in 2014-2017. In aggregate, health costs attributable to metastatic prostate cancer are $5.2 to $8.2 billion per year. CONCLUSIONS: The per patient annual health care costs attributable to metastatic prostate cancer are substantial and have increased over time, corresponding to the approval of new oral therapies used in treating metastatic prostate cancer.

Prolonged Opioid Use Following Bladder Tumor Resection for Opioid-naïve Patients.

INTRODUCTION: Bladder cancer patients represent a high-risk group for opioid dependence due to the frequency of surgical procedures. Using MarketScan insurance commercial claims and Medicare-eligible databases, we sought to identify whether filling an opioid prescription following initial transurethral resection of bladder tumor resulted in increased odds of prolonged opioid use. METHODS: We analyzed 43,741 commercial claims and 45,828 Medicare-eligible opioid-naïve patients with a new diagnosis of bladder cancer from 2009 to 2019. Multivariable analyses were completed to assess the odds of prolonged opioid use at 3-6 months based on initial exposure to opioids and initial opioid dose quartile. We performed subgroup analyses by sex and eventual treatment modality. RESULTS: Those who filled an opioid prescription following initial transurethral resection of bladder tumor had greater odds of persistent opioid use (commercial claims: 27% vs 12%, OR 2.14, 95% CI 1.84-2.45; Medicare-eligible: 24% vs 12%, OR 1.95, 95% CI 1.70-2.22). Increasing dosage quartile of opioids was associated with increased odds of prolonged opioid use. Those going on to radical therapy had the highest rates of an initial opioid prescription (31% commercial claims and 23% Medicare eligible). Men and women had similar rates of initial prescriptions, but female sex was associated with higher odds of persistent opioid use at 3-6 months in the Medicare-eligible group (OR 1.08, 95% CI 1.01-1.16). CONCLUSIONS: Opioids following initial transurethral resection of bladder tumor increase the odds of continued use at 3-6 months, with the greatest odds in those prescribed the highest initial doses. These data suggest that short-term prescriptions have long-term effects, and additional research on opioid use and bladder cancer outcomes is merited.

Dietary Patterns and Risk of Gleason Grade Progression among Men on Active Surveillance for Prostate Cancer: Results from the Canary Prostate Active Surveillance Study.

Modifiable lifestyle factors, such as following a healthy dietary pattern may delay or prevent prostate cancer (PCa) progression. However, few studies have evaluated whether following specific dietary patterns after PCa diagnosis impacts risk of disease progression among men with localized PCa managed by active surveillance (AS). 564 men enrolled in the Canary Prostate Active Surveillance Study, a protocol-driven AS study utilizing a pre-specified prostate-specific antigen monitoring and surveillance biopsy regimen, completed a food frequency questionnaire (FFQ) at enrollment and had ≥ 1 surveillance biopsy during follow-up. FFQs were used to evaluate adherence to the Dietary Guidelines for Americans (Healthy Eating index (HEI))-2015, alternative Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) dietary patterns. Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals were estimated using Cox proportional hazards models. During a median follow-up of 7.8 years, 237 men experienced an increase in Gleason score on subsequent biopsy (grade reclassification). Higher HEI-2015, aMED or DASH diet scores after diagnosis were not associated with significant reductions in the risk of grade reclassification during AS. However, these dietary patterns have well-established protective effects on chronic diseases and mortality and remain a prudent choice for men with prostate cancer managed by AS.

Trends in Urethral Suspension With Robotic Prostatectomy Procedures Following Medicare Payment Policy Changes.

Importance: In 2016, the Centers for Medicare and Medicaid Services cut payments for robotic prostatectomy performed for Medicare beneficiaries. Although regulations mandate that billing for urethral suspension is only acceptable for preexisting urinary incontinence, reductions in reimbursement may incentivize billing for the use of this procedure in other scenarios. Objective: To assess trends and geographic variations in payments for urethral suspension with robotic prostatectomy in the context of Medicare payment policy. Design, Setting, and Participants: This US population-based retrospective cohort study analyzed data from the IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental Database for men with employer-based insurance (primary commercial or Medicare supplemental coverage) who underwent robotic prostatectomy (Current Procedural Terminology [CPT] code 55866) between 2009 and 2019. Exposures: Time period and metropolitan statistical area of patient residence. Main Outcomes and Measures: Payment for urethral suspension (CPT code 51990) with robotic prostatectomy. Results: We identified 87 774 men with prostate cancer treated with robotic prostatectomy; 3352 (3.8%) had undergone urethral suspension. The mean (SD) patient age was 59.7 (6.5) years; 16 870 patients (19.2%) had Medicare supplemental coverage. From 2015 to 2016, median payments for robotic prostatectomy changed by -$358 (-17.0%) for Medicare beneficiaries vs -$9 (0%) for commercially insured patients. With urethral suspension vs without, median (IQR) episode payments for robotic prostatectomy were higher for commercially insured men ($3678 [$3090-$4503] vs $3322 [$2601-$4306]) and Medicare beneficiaries ($2927 [$2450-$3909] vs $2379 [$2014-$3512]). Compared with men treated between 2013 and 2015, those treated between 2016 and 2017 were twice as likely to undergo urethral suspension (8.5% vs 4.1%; odds ratio, 2.17 [95% CI, 1.96-2.38]). The proportion of patients who underwent urethral suspension was stable for 2018 to 2019 and 2016 to 2017 (8.5% vs 9.0%; odds ratio, 1.06 [95% CI, 0.96-1.18]). From 2015 to 2019, the proportion of patients who underwent urethral suspension was highest in Charleston, South Carolina (92.0%), Knoxville, Tennessee (66.0%), and Columbia, South Carolina (58.0%). These regions neighbored high-volume areas without patients who underwent prostatectomy with urethral suspension (eg, 146 patients in Greenville, South Carolina, and 173 in Nashville, Tennessee). Conclusions and Relevance: In this study, urethral suspension was associated with increased costs for patients with both commercial insurance and Medicare. Patients treated between 2016 and 2017 were more likely than those treated between 2013 and 2015 to undergo this procedure. Geographic variation in use exceeded what was expected for the preexisting condition for which billing is permitted for Medicare beneficiaries. Policy statements from professional societies highlighting appropriate billing for urethral suspension may have tempered, but not reversed, the broad adoption of this procedure.

Concordance between influential adverse treatment outcomes and localized prostate cancer treatment decisions.

BACKGROUND: Although treatment decisions for localized prostate cancer (LPC) are preference-sensitive, the extent to which individuals with LPC receive preference-concordant treatment is unclear. In a sample of individuals with LPC, the purpose of this study was to (a) assess concordance between the influence of potential adverse treatment outcomes and treatment choice; (b) determine whether receipt of a decision aid predicts higher odds of concordance; and (c) identify predictors of concordance from a set of participant characteristics and influential personal factors. METHODS: Participants reported the influence of potential adverse treatment outcomes and personal factors on treatment decisions at baseline. Preference-concordant treatment was defined as (a) any treatment if risk of adverse outcomes did not have a lot of influence, (b) active surveillance if risk of adverse outcomes had a lot of influence, or (c) radical prostatectomy or active surveillance if risk of adverse bowel outcomes had a lot of influence and risk of other adverse outcomes did not have a lot of influence. Data were analyzed using descriptive statistics and logistic regression. RESULTS: Of 224 participants, 137 (61%) pursued treatment concordant with preferences related to adverse treatment outcomes. Receipt of a decision aid did not predict higher odds of concordance. Low tumor risk and age ≥ 60 years predicted higher odds of concordance, while attributing a lot of influence to the impact of treatment on recreation predicted lower odds of concordance. CONCLUSIONS: Risk of potential adverse treatment outcomes may not be the foremost consideration of some patients with LPC. Assessment of the relative importance of patients' stated values and preferences is warranted in the setting of LPC treatment decision making. CLINICAL TRIAL REGISTRATION: NCT01844999 ( www. CLINICALTRIALS: gov ).

Multi-institutional analysis of clinical and imaging risk factors for detecting clinically significant prostate cancer in men with PI-RADS 3 lesions.

BACKGROUND: Most Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions do not contain clinically significant prostate cancer (CSPCa; grade group ≥2). This study was aimed at identifying clinical and magnetic resonance imaging (MRI)-derived risk fac- tors that predict CSPCa in men with PI-RADS 3 lesions. METHODS: This study analyzed the detection of CSPCa in men who underwent MRI-targeted biopsy for PI-RADS 3 lesions. Multivariable logistic regression models with goodness-of-fit testing were used to identify variables associated with CSPCa. Receiver operating curves and decision curve analyses were used to estimate the clinical utility of a predictive model. RESULTS: Of the 1784 men reviewed, 1537 were included in the training cohort, and 247 were included in the validation cohort. The 309 men with CSPCa (17.3%) were older, had a higher prostate-specific antigen (PSA) density, and had a greater likelihood of an anteriorly located lesion than men without CSPCa (p < .01). Multivariable analysis revealed that PSA density (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.05-1.85; p < .01), age (OR, 1.05; 95% CI, 1.02-1.07; p < .01), and a biopsy-naive status (OR, 1.83; 95% CI, 1.38-2.44) were independently associated with CSPCa. A prior negative biopsy was negatively associated (OR, 0.35; 95% CI, 0.24-0.50; p < .01). The application of the model to the validation cohort resulted in an area under the curve of 0.78. A predicted risk threshold of 12% could have prevented 25% of biopsies while detecting almost 95% of CSPCas with a sensitivity of 94% and a specificity of 34%. CONCLUSIONS: For PI-RADS 3 lesions, an elevated PSA density, older age, and a biopsy-naive status were associated with CSPCa, whereas a prior negative biopsy was negatively associated. A predictive model could prevent PI-RADS 3 biopsies while missing few CSPCas. LAY SUMMARY: Among men with an equivocal lesion (Prostate Imaging-Reporting and Data System 3) on multiparametric magnetic resonance imaging (mpMRI), those who are older, those who have a higher prostate-specific antigen density, and those who have never had a biopsy before are at higher risk for having clinically significant prostate cancer (CSPCa) on subsequent biopsy. However, men with at least one negative biopsy have a lower risk of CSPCa. A new predictive model can greatly reduce the need to biopsy equivocal lesions noted on mpMRI while missing only a few cases of CSPCa.

Impact of Prostate Health Index Results for Prediction of Biopsy Grade Reclassification During Active Surveillance.

PURPOSE: We assessed whether Prostate Health Index results improve prediction of grade reclassification for men on active surveillance. METHODS AND MATERIALS: We identified men in Canary Prostate Active Surveillance Study with Grade Group 1 cancer. Outcome was grade reclassification to Grade Group 2+ cancer. We considered decision rules to maximize specificity with sensitivity set at 95%. We derived rules based on clinical data (R1) vs clinical data+Prostate Health Index (R3). We considered an "or"-logic rule combining clinical score and Prostate Health Index (R4), and a "2-step" rule using clinical data followed by risk stratification based on Prostate Health Index (R2). Rules were applied to a validation set, where values of R2-R4 vs R1 for specificity and sensitivity were evaluated. RESULTS: We included 1,532 biopsies (n = 610 discovery; n = 922 validation) among 1,142 men. Grade reclassification was seen in 27% of biopsies (23% discovery, 29% validation). Among the discovery set, at 95% sensitivity, R2 yielded highest specificity at 27% vs 17% for R1. In the validation set, R3 had best performance vs R1 with Δsensitivity = -4% and Δspecificity = +6%. There was slight improvement for R3 vs R1 for confirmatory biopsy (AUC 0.745 vs R1 0.724, ΔAUC 0.021, 95% CI 0.002-0.041) but not for subsequent biopsies (ΔAUC -0.012, 95% CI -0.031-0.006). R3 did not have better discrimination vs R1 among the biopsy cohort overall (ΔAUC 0.007, 95% CI -0.007-0.020). CONCLUSIONS: Among active surveillance patients, using Prostate Health Index with clinical data modestly improved prediction of grade reclassification on confirmatory biopsy and did not improve prediction on subsequent biopsies.

Germline mutations in penetrant cancer predisposition genes are rare in men with prostate cancer selecting active surveillance.

BACKGROUND: Pathogenic germline mutations in several rare penetrant cancer predisposition genes are associated with an increased risk of aggressive prostate cancer (PC). Our objectives were to determine the prevalence of pathogenic germline mutations in men with low-risk PC on active surveillance, and assess whether pathogenic germline mutations associate with grade reclassification or adverse pathology, recurrence, or metastases, in men treated after initial surveillance. METHODS: Men prospectively enrolled in the Canary Prostate Active Surveillance Study (PASS) were retrospectively sampled for the study. Germline DNA was sequenced utilizing a hereditary cancer gene panel. Mutations were classified according to the American College of Clinical Genetics and Genomics' guidelines. The association of pathogenic germline mutations with grade reclassification and adverse characteristics was evaluated by weighted Cox proportional hazards modeling and conditional logistic regression, respectively. RESULTS: Overall, 29 of 437 (6.6%) study participants harbored a pathogenic germline mutation of which 19 occurred in a gene involved in DNA repair (4.3%). Eight participants (1.8%) had pathogenic germline mutations in three genes associated with aggressive PC: ATM, BRCA1, and BRCA2. The presence of pathogenic germline mutations in DNA repair genes did not associate with adverse characteristics (univariate analysis HR = 0.87, 95% CI: 0.36-2.06, p = 0.7). The carrier rates of pathogenic germline mutations in ATM, BRCA1, and BRCA2did not differ in men with or without grade reclassification (1.9% vs. 1.8%). CONCLUSION: The frequency of pathogenic germline mutations in penetrant cancer predisposition genes is extremely low in men with PC undergoing active surveillance and pathogenic germline mutations had no apparent association with grade reclassification or adverse characteristics.

Treatment Patterns and Overall Survival Outcomes Among Patients Aged 80 yr or Older with High-risk Prostate Cancer.

BACKGROUND: Elderly patients diagnosed with high-risk prostate cancer (PCa) present a therapeutic dilemma of balancing treatment of a potentially lethal malignancy with overtreatment of a cancer that may not threaten life expectancy. OBJECTIVE: To investigate treatment patterns and overall survival outcomes in this group of patients. DESIGN SETTING AND PARTICIPANTS: A retrospective cohort study was conducted. We queried the National Cancer Database for high-risk PCa in patients aged 80 yr or older diagnosed during 2004-2016. INTERVENTION: Eligible patients underwent no treatment following biopsy (ie, observation), androgen deprivation therapy (ADT) alone, radiation therapy (RT) alone, RT + ADT, or surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier, log rank, and multivariate Cox proportional hazard regression was performed to compare overall survival (OS). RESULTS AND LIMITATIONS: A total of 19 920 men were eligible for analysis, and the most common treatment approach was RT + ADT (7401 patients; 37.2%). Observation and ADT alone declined over time (59.3% in 2004 vs 47.5% in 2016). There was no observed difference in OS between observation and ADT alone (adjusted hazard ratio [HR] 1.04, 95% confidence interval [CI], 0.99-1.09; p = 0.105). Definitive local treatment was associated with improved OS compared with ADT alone (RT alone, HR 0.54, 95% CI, 0.50-0.59, p < 0.0001; ADT + RT, HR 0.48, 95% CI, 0.46-0.50, p < 0.0001; surgery, HR 0.50, 95% CI, 0.42-0.59, p < 0.0001). CONCLUSIONS: This analysis demonstrates that the use of definitive local therapy, including surgery or RT ± ADT, is increasing and is associated with a 50% reduction in overall mortality compared with observation or ADT alone. While prospective validation is warranted, elderly men with high-risk disease eligible for definitive management should be counseled on the risks, including a possible compromise in OS, with deferring definitive management. PATIENT SUMMARY: Elderly men are more often diagnosed with higher-risk prostate cancer but are less likely to receive curative treatment options than younger men. Our analysis demonstrates that for men ≥80 yr of age with high-risk prostate cancer, definitive local therapy, including surgery or radiation therapy and/or androgen deprivation therapy, is associated with a 50% reduction in overall mortality compared with observation or androgen deprivation therapy alone. We therefore recommend that life expectancy (ie, physiologic age) be taken into account, over chronologic age, and that elderly men with good life expectancy (eg, >5 yr; minimal comorbidity) should be offered definitive, life-prolonging therapy.

Evaluating the Outcomes of Active Surveillance in Grade Group 2 Prostate Cancer: Prospective Results from the Canary PASS Cohort.

PURPOSE: Active surveillance (AS) for grade group (GG) 2 patients is not yet well defined. We sought to compare clinical outcomes of men with GG1 and GG2 prostate cancer undergoing AS in a large prospective North American cohort. MATERIALS AND METHODS: Participants were prospectively enrolled in an AS study with protocol-directed followup at 10 centers in the U.S. and Canada. We evaluated time from diagnosis to biopsy grade reclassification and time to treatment. In men treated after initial surveillance, adverse pathology and recurrence were also analyzed. RESULTS: At diagnosis, 154 (9%) had GG2 and 1,574 (91%) had GG1. Five-year reclassification rates were similar between GG2 and GG1 (30% vs 37%, p=0.11). However, more patients with GG2 were treated at 5 years (58% vs 34%, p <0.001) and GG at diagnosis was associated with time to treatment (HR=1.41; p=0.01). Treatment rates were similar in patients who reclassified during AS, but in patients who did not reclassify, those diagnosed with GG2 underwent definitive treatment more often than GG1 (5-year treatment rates 52% and 12%, p <0.0001). In participants who underwent radical prostatectomy after initial surveillance, the adjusted risk of adverse pathology was similar (HR=1.26; p=0.4). Biochemical recurrence within 3 years of treatment for GG2 and GG1 patients was 6% for both groups. CONCLUSIONS: In patients on AS, the rate of definitive treatment is higher after an initial diagnosis of GG2 than GG1. Adverse pathology after radical prostatectomy and short-term biochemical recurrence after definitive treatment were similar between GG2 and GG1.