Phase II trial of CV301 vaccine combined with atezolizumab in advanced urothelial carcinoma.

CV301 comprises recombinant poxviruses, Modified Vaccinia Ankara (MVA) and Fowlpox (FPV), encoding CEA, MUC-1, and co-stimulatory Molecules (TRICOM) ICAM-1, LFA-3, and B7-1. MVA-BN-CV301 is used for priming and FPV-CV301 is used for boosting. A Phase 2, single-arm trial was designed to evaluate CV301 plus atezolizumab as first-line treatment for cisplatin-ineligible advanced urothelial carcinoma (aUC) (Cohort 1) or progressing after platinum chemotherapy (Cohort 2). MVA-CV301 was given subcutaneously (SC) on Days 1 and 22 and FPV-CV301 SC from day 43 every 21 days for 4 doses, then tapered gradually over up to 2 years. Atezolizumab 1200 mg IV was given every 21 days. The primary endpoint was objective response rate (ORR). Overall, 43 evaluable patients received therapy: 19 in Cohort 1; 24 in Cohort 2; nine experienced ≥ Grade 3 therapy-related adverse events. In Cohort 1, one had partial response (PR) (ORR 5.3%, 90% CI 0.3, 22.6). In Cohort 2, 1 complete response and 1 PR were noted (ORR 8.3%, 90% CI 1.5, 24.0). The trial was halted for futility. Patients exhibiting benefit demonstrated T-cell response to CEA and MUC-1. The trial illustrates the challenges in the development of vaccines, which should be guided by robust preclinical data.

Higher SUVmax on FDG-PET is associated with shorter survival in adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive, rare malignancy. 2-deoxy-2-[18F]-fluoro-d-glucose positron emission tomography (FDG-PET) assesses tumor metabolism and glucose utilization. We hypothesized that higher maximum standard uptake value (SUVmax) is associated with decreased survival. METHODS: We performed a retrospective analysis of patients with ACC. Included patients (n = 26) had an FDG-PET scan available with a documentable SUVmax. Patients were dichotomized into "High" (≥8.4, n = 12) and "Low" (<8.4, n = 14) SUVmax. Univariate analysis and survival analysis were performed to compare groups. RESULTS: Demographics between groups were equivalent. The high SUVmax cohort demonstrated lower survival (median 479 days or 15.7 months) compared to the low group (median 1490 days or 48.6 months, p = .01). Log-Rank curve confirmed differences in survival (p = .007). CONCLUSIONS: Higher SUVmax was associated with significantly worse survival in ACC and may reflect a more aggressive phenotype. FDG-PET may provide clinically useful information to determine prognosis and treatment. Further studies should prospectively evaluate using FDG-PET/CT in ACC.

Longitudinal Evaluation of Circulating Tumor DNA Using Sensitive Amplicon-Based Next-Generation Sequencing to Identify Resistance Mechanisms to Immune Checkpoint Inhibitors for Advanced Urothelial Carcinoma.

Serial evaluation of circulating tumor DNA may allow noninvasive assessment of drivers of resistance to immune checkpoint inhibitors (ICIs) in advanced urothelial cancer (aUC). We used a novel, amplicon-based next-generation sequencing assay to identify genomic alterations (GAs) pre- and post-therapy in 39 patients with aUC receiving ICI and 6 receiving platinum-based chemotherapy (PBC). One or more GA was seen in 95% and 100% of pre- and post-ICI samples, respectively, commonly in TP53 (54% and 54%), TERT (49% and 59%), and BRCA1/BRCA2 (33% and 33%). Clearance of ≥1 GA was seen in 7 of 9 patients responding to ICI, commonly in TP53 (n = 4), PIK3CA (n = 2), and BRCA1/BRCA2 (n = 2). A new GA was seen in 17 of 20 patients progressing on ICI, frequently in BRCA1/BRCA2 (n = 6), PIK3CA (n = 3), and TP53 (n = 3), which seldom emerged in patients receiving PBC. These findings highlight the potential for longitudinal circulating tumor DNA evaluation in tracking response and resistance to therapy.

Biomarker-Based Phase II Study of Sapanisertib (TAK-228): An mTORC1/2 Inhibitor in Patients With Refractory Metastatic Renal Cell Carcinoma.

PURPOSE: Sapanisertib is a kinase inhibitor that inhibits both mammalian target of rapamycin complex 1 (mTORC1) and mTORC2. In this multicenter, single-arm phase II trial, we evaluated the efficacy of sapanisertib in patients with treatment-refractory metastatic renal cell carcinoma (mRCC; NCT03097328). METHODS: Patients with mRCC of any histology progressing through standard therapy (including prior mTOR inhibitors) had baseline biopsy and received sapanisertib 30 mg by mouth once weekly until unacceptable toxicity or disease progression. The primary end point was objective response rate by RECIST 1.1. Tissue biomarkers of mTOR pathway activation were explored. RESULTS: We enrolled 38 patients with mRCC (clear cell = 28; variant histology = 10) between August 2017 and November 2019. Twenty-four (63%) had received ≥ 3 prior lines of therapy; 17 (45%) had received prior rapalog therapy. The median follow-up was 10.4 (range 1-27.4) months. Objective response rate was two of 38 (5.3%; 90% CI, 1 to 15.6); the median progression-free survival (PFS) was 2.5 months (95% CI, 1.8 to 3.7). Twelve patients (32%) developed treatment-related grade 3 adverse events, with no grade 4 or 5 toxicities. Alterations in the mTOR pathway genes were seen in 5 of 29 evaluable patients (MTOR n = 1, PTEN n = 3, and TSC1 n = 1) with no association with response or PFS. Diminished or loss of PTEN expression by immunohistochemistry was seen in 8 of 21 patients and trended toward shorter PFS compared with intact PTEN (median 1.9 v 3.7 months; hazard ratio 2.5; 95% CI, 0.9 to 6.7; P = .055). CONCLUSION: Sapanisertib had minimal activity in treatment-refractory mRCC independent of mTOR pathway alterations. Additional therapeutic strategies are needed for patients with refractory mRCC.

Cardiovascular toxicities associated with abiraterone compared to enzalutamide-A pharmacovigilance study.

BACKGROUND: Androgen deprivation therapy (ADT) is standard-of-care for advanced prostate cancer. Studies have generally found increased cardiovascular risks associated with ADT, but the comparative risk of newer agents is under-characterized. We defined the cardiac risks of abiraterone and enzalutamide, using gonadotropic releasing hormone (GnRH) agonists to establish baseline ADT risk. METHODS: We used VigiBase, the World Health Organization pharmacovigilance database, to identify cardiac adverse drug reactions (ADRs) in a cohort taking GnRH agonists, abiraterone, or enzalutamide therapy for prostate cancer, comparing them to all other patients. To examine the relationship, we used an empirical Bayes estimator to screen for significance, then calculated the reporting odds ratio (ROR), a surrogate measure of association. A lower bound of a 95% confidence interval (CI) of ROR > 1 reflects a disproportionality signal that more ADRs are observed than expected due to chance. FINDINGS: We identified 2,433 cardiac ADRs, with higher odds for abiraterone compared to all other VigiBase drugs for overall cardiac events (ROR 1•59, 95% CI 1•48-1•71), myocardial infarction (1•35, 1•16-1•58), arrythmia (2•04, 1•82-2•30), and heart failure (3•02, 2•60-3•51), but found no signal for enzalutamide. Patients on GnRH agonists also had increased risk of cardiac events (ROR 1•21, 95% CI 1•12-1•30), myocardial infarction (1•80, 1•61-2•03) and heart failure (2•06, 1•76-2•41). INTERPRETATION: We found higher reported odds of cardiac events for abiraterone but not enzalutamide. Our data may suggest that patients with significant cardiac comorbidities may be better-suited for therapy with enzalutamide over abiraterone. FUNDING: None.

Risk of Immune-related Adverse Events in Melanoma Patients With Preexisting Autoimmune Disease Treated With Immune Checkpoint Inhibitors: A Population-based Study Using SEER-Medicare Data.

OBJECTIVE: The objective of this study was to examine the risk of immune-related adverse events (irAEs) in patients with a preexisting autoimmune disease (pAID) presenting with a cutaneous melanoma receiving an immune checkpoint inhibitor (ICI) therapy. METHODS: Data from the Surveillance, Epidemiology, and End Results cancer registries and linked Medicare claims between January 2010 and December 2015 was used to identify patients diagnosed with cutaneous melanoma who had pAID or received ICI or both. Patients were then stratified into 3 groups: ICI+pAID, non-ICI+pAID, and ICI+non-pAID. Inverse probability of treatment weighted Cox proportional hazards regression models were fitted to assess the risk of cardiac, pulmonary, endocrine, and neurological irAE. RESULTS: In total, 3704 individuals were included in the analysis. The majority of patients consisted of non-ICI+pAID patients (N=2706/73.1%), while 106 (2.9%) patients and 892 (24.1%) were classified as ICI+pAID and ICI+non-pAID, respectively. The risk of irAE was higher in the ICI+pAID group compared with the non-ICI+pAID and ICI+non-pAID, respectively (non-ICI: cardiac: hazard ratio [HR]=3.59, 95% confidence interval [CI]: 2.83-4.55; pulmonary: HR=3.94, 95% CI: 3.23-4.81; endocrine: HR=1.72, 95% CI: 1.53-1.93; neurological: HR=3.88, 95% CI: 2.30-6.57/non-pAID: cardiac: HR=3.83, 95% CI: 3.39-4.32; pulmonary: HR=2.08, 95% CI: 1.87-2.32; endocrine: HR=1.23, 95% CI: 1.14-1.32; neurological: HR=3.77, 95% CI: 2.75-5.18). CONCLUSIONS: Patients with a pAID face a significantly higher risk of irAEs. Further research examining the clinical impact of these events on the patients' oncological outcome and quality of life is urgently needed given our findings of significantly worse rates of adverse events.

The Relationship Between Health Literacy and Nonrecommended Cancer Screening.

INTRODUCTION: Health literacy affects how patients behave within the healthcare system. Overutilization of screening procedures inconsistent with the U.S. Preventive Services Task Force guidelines contributes to the high cost of health care. The authors hypothesize that higher health literacy supports guideline-concordant screening. This study assesses the effect of health literacy on nonrecommended prostate, breast, and cervical cancer screening in patients older than the recommended screening age limit. METHODS: The 2016 Behavioral Risk Factor Surveillance System included health literacy modules. Respondents self-reported their ability to obtain and understand health information, resulting in 4 health literacy rankings. The authors calculated the population-weighted proportion of respondents in each health literacy category who underwent screening past the Task Force‒recommended age limit. The ORs of nonrecommended screening for each malignancy were calculated, with low health literacy as the ref category. RESULTS: Individuals with higher health literacy underwent more nonrecommended screening. Nonrecommended prostate cancer screening was performed in 27.4% (95% CI=23.7%, 31.4%) and 47.7% (95% CI=44.1%, 51.3%) of respondents with low and high health literacy, respectively (p<0.001). Nonrecommended breast cancer screening was performed in 46.8% (95% CI=42.6%, 51.1%) and 67.7% (95% CI=64.2%, 71.1%) of respondents with low and high health literacy, respectively (p=0.002). Nonrecommended cervical cancer screening was performed in 33.8% (95% CI=31.1%, 36.5%) and 48.4% (95% CI=46.3%, 50.5%) of respondents with low and high health literacy, respectively (p<0.001). Individuals with high health literacy were significantly more likely than those with low health literacy to screen against the recommendations for prostate (OR=1.73, 95% CI=1.34, 2.23, p<0.001), cervical (OR=1.533, 95% CI=1.31, 1.80, p<0.001), and breast (OR=8.213, 95% CI=4.90, 13.76, p<0.001) cancer. CONCLUSIONS: Higher health literacy correlates with increased rates of screening beyond the recommended age, contrary to the study hypothesis. Breast cancer demonstrated the highest rates of nonrecommended screening.

Results of a multicenter, phase 2 study of nivolumab and ipilimumab for patients with advanced rare genitourinary malignancies.

BACKGROUND: In this multicenter, single-arm, multicohort, phase 2 trial, the efficacy of nivolumab and ipilimumab was evaluated in patients with advanced rare genitourinary cancers, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, platinum-refractory germ cell tumors, penile carcinoma, and prostate cancer of variant histology (NCT03333616). METHODS: Patients with rare genitourinary malignancies and no prior immune checkpoint inhibitor exposure were enrolled. Patients received nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg intravenously every 3 weeks for 4 doses, and this was followed by 480 mg of nivolumab intravenously every 4 weeks. The primary endpoint was the objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors (version 1.1). RESULTS: Fifty-five patients were enrolled at 6 institutions between April 2018 and July 2019 in 3 cohorts: BUTCVH (n = 19), adrenal tumors (n = 18), and other tumors (n = 18). The median follow-up was 9.9 months (range, 1 to 21 months). Twenty-eight patients (51%) received 4 doses of nivolumab and ipilimumab; 25 patients received nivolumab maintenance for a median of 4 cycles (range, 1-18 cycles). The ORR for the entire study was 16% (80% confidence interval, 10%-25%); the ORR in the BUTCVH cohort, including 2 complete responses, was 37%, and it was 6% in the other 2 cohorts. Twenty-two patients (40%) developed treatment-related grade 3 or higher toxicities; 24% (n = 13) required high-dose steroids (≥40 mg of prednisone or the equivalent). Grade 5 events occurred in 3 patients; 1 death was treatment related. CONCLUSIONS: Nivolumab and ipilimumab resulted in objective responses in a subset of patients with rare genitourinary malignancies, especially those with BUTCVH. An additional cohort exploring their activity in genitourinary tumors with neuroendocrine differentiation is ongoing. LAY SUMMARY: Patients with rare cancers are often excluded from studies and have limited treatment options. Fifty-five patients with rare tumors of the genitourinary system were enrolled from multiple sites and were treated with nivolumab and ipilimumab, a regimen used for kidney cancer. The regimen showed activity in some patients, particularly those with bladder or upper tract cancers of unusual or variant histology; 37% of those patients responded to therapy. Additional studies are ongoing to better determine who benefits the most from this combination.

Impact of health literacy on shared decision making for prostate-specific antigen screening in the United States.

BACKGROUND: Current guidelines endorse shared decision making (SDM) for prostate-specific antigen (PSA) screening. The relationship between a patient's health literacy (HL) and SDM remains unclear. In the current study, the authors sought to identify the impact of HL on the rates of PSA screening and on the relationship between HL and SDM following the 2012 US Preventive Services Task Force recommendations against PSA screening. METHODS: Using data from the 2016 Behavioral Risk Factor Surveillance System, the authors examined PSA screening in the 13 states that administered the optional "Health Literacy" module. Men aged ≥50 years were examined. Complex samples multivariable logistic regression models were computed to assess the odds of undergoing PSA screening. The interactions between HL and SDM were also examined. RESULTS: A weighted sample of 12.249 million men with a rate of PSA screening of 33.4% were identified. Approximately one-third self-identified as having optimal HL. Rates of PSA screening were found to be highest amongst the highest HL group (42.2%). Being in this group was a significant predictor of undergoing PSA screening (odds ratio, 1.214; 95% confidence interval, 1.051-1.403). There was a significant interaction observed between HL and SDM (P for interaction, <.001) such that higher HL was associated with a lower likelihood of undergoing PSA screening when SDM was present. CONCLUSIONS: In the uncertain environment of multiple contradictory screening guidelines, men who reported higher levels of HL were found to have higher levels of screening. The authors demonstrated that increased HL may reduce the screening-promoting effect of SDM. These findings highlight the dynamic interplay between HL and SDM that should inform the creation and promulgation of SDM guidelines, specifically when considering patients with low HL.

Mobile Health App for Prostate Cancer Patients on Androgen Deprivation Therapy: Qualitative Usability Study.

BACKGROUND: Androgen deprivation therapy (ADT) increases the risk of metabolic adverse effects among patients with prostate cancer. The transformative impact of mobile health (mHealth) apps may benefit men managing activity and nutrition at home. OBJECTIVE: This study aimed to evaluate the usability and patient experience of a newly developed mHealth app among prostate cancer patients on ADT and physicians' beliefs about the potential benefits of using this app. METHODS: This study took place over 2 months, beginning in March 2019. A sample of 5 patients (age 45-75 years) initiating ADT participated in a semistructured focus group discussion with a facilitator. The study participants also included 5 specialist physicians who provided in-depth interviews. An institutional review board-approved script was used to guide both the focus group and physician interviews. Usability was tested through specific scenarios presented to the patients, including downloading the mHealth app, entering information on physical activity and meals, and navigating the app. The focus group and interviews were audio recorded and transcribed. Content analysis was used to analyze the transcripts iteratively and exhaustively. Thematic discrepancies between reviewers were resolved through consensus. RESULTS: The mean age of the patients was 62 years. This group included 4 White and 1 Latin American patients. The physician specialists included 2 urologists, 2 medical oncologists, and 1 radiation oncologist. Analyses revealed that the patients appreciated the holistic care enabled by the app. Difficulties were observed with registration of the app among 60% (3/5) of the patients; however, all the patients were able to input information about their physical activity and navigate the options within the app. Most patients (4/5, 80%) were able to input data on their recent meal. Among the health care physicians, the dominant themes reflected in the interviews included undermining of patients ability to use technology, patients' fear of technology, and concern for the ability of older patients to access technology. CONCLUSIONS: The patients reported an overall positive experience of using an mHealth app to record and track diet and exercise. Usability was observed to be an important factor for adoption and was determined by ease of registration and use, intuitive appearance of the app, and focus on holistic cancer care. The physicians believed that the app was easy to use but raised concerns about usability among older men who may not typically use smartphone apps.

Conditional immune toxicity rate in patients with metastatic renal and urothelial cancer treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs). Although the incidence and prevalence of irAEs have been well characterized in the literature, less is known about the cumulative incidence rate of irAEs. We studied the cumulative incidence of irAEs, defined as the probability of irAE occurrence over time and the risk factors for irAE development in metastatic urothelial carcinoma (mUC) and renal cell carcinoma (mRCC) patients treated with ICIs. METHODS: We identified a cohort of patients who received ICIs for mUC and mRCC. irAEs were classified using Common Terminology Criteria for Adverse Event (CTCAE) V.5.0 guidelines. The monthly incidence of irAEs over time was reported after landmark duration of therapy. Cumulative incidence of irAEs was calculated to evaluate the time to the first occurrence of an irAE accounting for the competing risk of death. Prognostic factors for irAE were assessed using the Fine and Gray method. RESULTS: A total of 470 patients were treated with ICIs between July 2013 and October 2018 (mUC: 199 (42.3%); mRCC: 271 (57.7%)). 341 (72.6%) patients received monotherapy, 86 (18.3%) received ICIs in combination with targeted therapies, and 43 (9.2%) received dual ICI therapy. Overall, 186 patients (39.5%) experienced an irAE at any time point. Common irAEs included hypothyroidism (n=42, 22.6%), rush and pruritus (n=36, 19.4%), diarrhea/colitis (n=35, 18.8%), transaminitis (n=32, 17.2%), and pneumonitis (n=14, 7.5%). Monthly incidence rates decreased over time; however, 17 of 109 (15.6%, 95% CI: 9.4% to 23.8%) experienced their first irAE at least 1 year after treatment initiation. No differences in cumulative incidence were observed based on cancer type, agent, or irAE grade. On multivariable analysis, combined ICI therapy with another ICI or with targeted therapy (p<0.001), first-line ICI therapy (p=0.011), and PD-1 inhibitor therapy (p=0.007) were all significantly associated with irAE development. CONCLUSIONS: This study quantitates the incidence of developing irAEs due to ICI conditioned on time elapsed without irAE development. Although the monthly incidence of irAEs decreased over time on therapy, patients can still develop delayed irAEs beyond ICI discontinuation, and thus, continuous vigilant monitoring is warranted.

Geographic Distribution of Racial Differences in Prostate Cancer Mortality.

Importance: While racial disparities in prostate cancer mortality are well documented, it is not well known how these disparities vary geographically within the US. Objective: To characterize geographic variation in prostate cancer-specific mortality differences between black and white men. Design, Setting, and Participants: This cohort study included data from 17 geographic registries within the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2007, to December 31, 2014. Inclusion criteria were men 18 years and older with biopsy-confirmed prostate cancer. Men missing data on key variables (ie, cancer stage, Gleason grade group, prostate-specific antigen level, and survival follow-up data) were excluded. Analysis was performed from September 5 to December 25, 2018. Exposure: Patient SEER-designated race (ie, black, white, or other). Main Outcomes and Measures: Fine and Gray competing-risks regression analyses were used to evaluate the difference in prostate-cancer specific mortality between black and white men. A stratified analysis by Gleason grade group was performed stratified as grade group 1 and grade groups 2 through 5. Results: The final cohort consisted of 229 771 men, including 178 204 white men (77.6%), 35 006 black men (15.2%), and 16 561 men of other or unknown race (7.2%). Mean (SD) age at diagnosis was 64.9 (8.8) years. There were 4773 prostate cancer deaths among white men and 1250 prostate cancer deaths among black men. Compared with white men, black men had a higher risk of mortality overall (adjusted hazard ratio [AHR], 1.39 [95% CI, 1.30-1.48]). In the stratified analysis, there were 4 registries in which black men had worse prostate cancer-specific survival in both Gleason grade group 1 (Atlanta, Georgia: AHR, 5.49 [95% CI, 2.03-14.87]; Greater Georgia: AHR, 1.88 [95% CI, 1.10-3.22]; Louisiana: AHR, 1.80 [95% CI, 1.06-3.07]; New Jersey: AHR, 2.60 [95% CI, 1.53-4.40]) and Gleason grade groups 2 through 5 (Atlanta: AHR, 1.88 [95% CI, 1.46-2.45]; Greater Georgia: AHR, 1.29 [95% CI, 1.07-1.56]; Louisiana: AHR, 1.28 [95% CI, 1.07-1.54]; New Jersey: AHR, 1.52 [95% CI, 1.24-1.87]), although the magnitude of survival difference was lower than for Gleason grade group 1 in each of these registries. The greatest race-based survival difference for men with Gleason grade group 1 disease was in the Atlanta registry. Conclusions and Relevance: These findings suggest that population-level differences in prostate cancer survival among black and white men were associated with a small set of geographic areas and with low-risk prostate cancer. Targeted interventions in these areas may help to mitigate prostate cancer care disparities at the national level.

Delayed nephrectomy has comparable long-term overall survival to immediate nephrectomy for cT1a renal cell carcinoma: A population-based analysis.

OBJECTIVES: Early surgical resection remains the recommended treatment option for most small renal mass (≤4 cm). We examined the long-term overall survival (OS) of patients managed with delayed and immediate nephrectomy of cT1a renal cancer. PATIENT AND METHODS: We utilized the National Cancer Database (2005-2010) to identify 14,677 patients (immediate nephrectomy: 14,050 patients vs. late nephrectomy: 627 patients) aged <70 years with Charlson Comorbidity Index 0 and cT1aN0M0 renal cell carcinoma. Immediate nephrectomy and late nephrectomy were defined as nephrectomy performed <30 days and >180 days from diagnosis, respectively. Inverse probability of treatment weighting-adjusted Kaplan-Meier curves and Cox proportional hazards regression analyses were used to compare OS of patients in the 2 treatment arms. Influence of patient age and Charlson Comorbidity Index on treatment effect was tested by interactions. Sensitivity analysis was performed to explore the outcome of delaying nephrectomy for >12 months. RESULTS: Median patient age was 55 years with a median follow-up of 82.5 months. Inverse probability of treatment weighting-adjusted Kaplan-Meier curves suggest no significant difference between treatment arms (immediate nephrectomy [<30 days] vs. delayed nephrectomy [>180 days]) (Hazard ratio 0.96; 95% confidence interval 0.73-1.26; P = 0.77). This outcome was consistent between all patients regardless of age (P = 0.48). Sensitivity analysis reports no difference in OS even if nephrectomy was delayed by >12 months (P = 0.60). CONCLUSIONS: We report that delayed and immediate nephrectomy for cT1a renal cell carcinoma confers comparable long-term OS. These findings suggest that a period of observation of between 6 and 12 months is safe to allow identification of renal masses, which will benefit from surgical resection.

The impact of underinsurance on bladder cancer diagnosis, survival, and care delivery for individuals under the age of 65 years.

BACKGROUND: Health insurance is a key mediator of health care disparities. Outcomes in bladder cancer, one of the costliest diseases to treat, may be especially sensitive to a patient's insurance status. METHODS: The Surveillance, Epidemiology, and End Results registry and the National Cancer Data Base were used to identify individuals younger than 65 years who were diagnosed with bladder cancer from 2007 to 2014. The associations between the insurance status (privately insured, insured by Medicaid, or uninsured) and the following outcomes were evaluated: diagnosis with advanced disease, cancer-specific survival, delay in treatment longer than 90 days, treatment in a high-volume hospital, and receipt of neoadjuvant chemotherapy (NAC). RESULTS: Compared with those with private insurance, uninsured and Medicaid-insured individuals were nearly twice as likely to receive a diagnosis of muscle-invasive bladder cancer (odds ratio [OR] for uninsured individuals, 1.90; 95% confidence interval [CI], 1.70-2.12; OR for Medicaid-insured individuals, 2.03; 95% CI, 1.87-2.20). They were also more likely to die of bladder cancer (adjusted hazard ratio [AHR] for uninsured individuals, 1.49; 95% CI, 1.31-1.71; AHR for Medicaid-insured individuals, 1.61; 95% CI, 1.46-1.79). Delays in treatment longer than 90 days were more likely for uninsured (OR, 1.36; 95% CI, 1.12-1.65) and Medicaid-insured individuals (OR, 1.22; 95% CI, 1.03-1.44) in comparison with the privately insured. Uninsured patients had lower odds of treatment at a high-volume facility, and Medicaid-insured patients had lower odds of receiving NAC (P < .001 for both). CONCLUSIONS: Compared with privately insured individuals, uninsured and Medicaid-insured individuals experience worse prognoses and poorer care quality. Expanding high-quality insurance coverage to marginalized populations may help to reduce the burden of this disease.

Facility-Level Variation in Pelvic Lymphadenectomy During Radical Prostatectomy and Effect on Overall Survival in Men with High-Risk Prostate Cancer.

PURPOSE: This study was designed to examine facility-level variation in the extent of pelvic lymphadenectomy and to determine whether more extensive lymphadenectomy is associated with a survival benefit among men with localized high-risk prostate cancer. METHODS: Using data from the National Cancer Data Base, we identified 13,652 men with a high predicted probability of 10-year survival (≤ 65 years of age and Charlson Comorbidity Index score of 0) who underwent radical prostatectomy at 1023 facilities for biopsy-confirmed localized high-risk prostate cancer diagnosed between January 2004 and December 2011. Multilevel, multinomial logistic regression was fitted to predict facility-level probability of receiving different extents of lymphadenectomy. Inverse probability of treatment weighting-adjusted Cox regression model with Bonferroni correction was fitted to compare risk of overall mortality. RESULTS: Overall, 11,284 (82.7%), 1601 (11.7%), and 767 (5.6%) men who underwent radical prostatectomy underwent concomitant none/limited lymphadenectomy (0-9 lymph nodes), standard lymphadenectomy (10-16 lymph nodes), and extended lymphadenectomy (≥ 17 lymph nodes), respectively. Extended lymphadenectomy was not associated with a survival benefit relative to standard lymphadenectomy (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.48-1.23; p = 0.4) nor no/limited lymphadenectomy (HR 0.77, 95% CI 0.87-2.20; p = 0.29) at a median follow-up of 83.3 months. Risk-adjusted facility-level predicted probabilities of extended, standard, or no/limited lymphadenectomy ranged from 0.01 to 52.6%, 3.3-53.3%, and 17.8-96.3%, respectively. CONCLUSIONS: We found significant facility-level variation in the extent of pelvic lymphadenectomy during radical prostatectomy despite no apparent survival benefit associated with more extensive lymphadenectomy. Further prospective data are needed to reevaluate the role of lymphadenectomy in the management of clinically localized prostate cancer.

Adoption of immunotherapy in the community for patients diagnosed with metastatic melanoma.

BACKGROUND: The introduction of immune checkpoint inhibitors has led to a survival benefit in patients with advanced melanoma; however data on the adoption of immunotherapy in the community are scarce. METHODS: Using the National Cancer Database, we identified 4725 patients aged ≥20 diagnosed with metastatic melanoma in the United States between 2011 and 2015. Multinomial regression was used to identify factors associated with the receipt of treatment at a low vs. high immunotherapy prescribing hospital, defined as the bottom and top quintile of hospitals according to their proportion of treating metastatic melanoma patients with immunotherapy. RESULTS: We identified 246 unique hospitals treating patients with metastatic melanoma. Between 2011 and 2015, the proportion of hospitals treating at least 20% of melanoma patients with immunotherapy within 90 days of diagnosis increased from 14.5 to 37.7%. The mean proportion of patients receiving immunotherapy was 7.8% (95% Confidence Interval [CI] 7.47-8.08) and 50.9% (95%-CI 47.6-54.3) in low and high prescribing hospitals, respectively. Predictors of receiving care in a low prescribing hospital included underinsurance (no insurance: relative risk ratio [RRR] 2.44, 95%-CI 1.28-4.67, p = 0.007; Medicaid: RRR 2.10, 95%-CI 1.12-3.92, p = 0.020), care in urban areas (RRR 2.58, 95%-CI 1.34-4.96, p = 0.005) and care at non-academic facilities (RRR 5.18, 95%CI 1.69-15.88, p = 0.004). CONCLUSION: While the use of immunotherapy for metastatic melanoma has increased over time, adoption varies widely across hospitals. Underinsured patients were more likely to receive treatment at low immunotherapy prescribing hospitals. The variation suggests inequity in access to these potentially life-saving drugs.

The current landscape of low-value care in men diagnosed with prostate cancer: what is the role of individual hospitals?

BACKGROUND: A considerable number of prostate cancer (PCa) patients eligible for expectant management receive definitive treatment. We aimed to investigate the hospital-level contribution to overtreatment in the United States. METHODS: Using the National Cancer Database we identified two nonoverlapping cohorts: (1) men with a life expectancy <10 years harbouring low or intermediate risk PCa (2) men with life expectancy ≥10 years with low-risk PCa. Multivariable mixed models with patient characteristics as fixed and hospital-level intercept as random effect were used to assess the hospital-level risk-adjusted probability of definitive treatment in both groups. Pearson's correlation coefficient was calculated to investigate the correlation between the hospitals probabilities of treating patients of both cohorts. RESULTS: We found 33,431 men with a life expectancy <10 years and 122,514 men with a life expectancy ≥10 years and low-risk PCa. In the latter, the probability of treatment ranged from 29.0% in the bottom to 90.0% in the top decile and from 35.0% to 88.0% for men with a life expectancy <10 years. Age and race were independent predictors of low-value treatment in both cohorts. The correlation between 1,225 hospitals treating men of both cohorts was strong (Pearson's r = 0.66, P < 0.001). CONCLUSION: There is wide hospital-level variability in low-value treatment of men with limited life expectancies and low-risk PCa. Hospitals more likely to treat men with limited life expectancies were more likely to treat men with low-risk PCa and vice versa. Identifying drivers and modifying practice at these hospitals may represent an effective tool for reducing overtreatment.

Association of Care at Minority-Serving vs Non-Minority-Serving Hospitals With Use of Palliative Care Among Racial/Ethnic Minorities With Metastatic Cancer in the United States.

Importance: It is not known whether racial/ethnic differences in receipt of palliative care are attributable to different treatment of minorities or lower utilization of palliative care at the relatively small number of hospitals that treat a large portion of minority patients. Objective: To assess the association of receipt of palliative care among patients with metastatic cancer with receipt of treatment at minority-serving hospitals (MSHs) vs non-MSHs. Design, Setting, and Participants: This retrospective cohort study used Participant Use Files of the National Cancer Database, a prospectively maintained, hospital-based cancer registry consisting of all patients treated at more than 1500 US hospitals, to collect data from individuals older than 40 years with metastatic prostate, lung, colon, and breast cancer, diagnosed from January 1, 2004, to December 31, 2015. Data were accessed in October 2017, and the analysis was performed in July 2018. Exposures: Hospitals in the top decile in terms of the proportion of black and Hispanic patients for each cancer type were defined as MSHs. Main Outcomes and Measures: A multilevel logistic regression model that estimated the odds of palliative care was fit, adjusting for year of diagnosis, sex, race/ethnicity, insurance, income, educational level, and cancer type, with an interaction term between cancer type and MSH status and a hospital-level random intercept to account for unmeasured hospital characteristics. Results: A total of 601 680 individuals (mean [SD] age, 67.4 [11.4] years; 95% CI, 67.2-67.6 years; 314 279 [52.2%] male; 475 039 [78.9%] white) were studied. In total, 130 813 patients (21.7%) received palliative care, ranging from 102 019 (25.4%) with lung cancer to 9966 (11.1%) with colon cancer. In total, 16 435 black individuals (20.0%) and 3551 Hispanic individuals (15.9%) received palliative care vs 106 603 non-Hispanic white individuals (22.5%) (P < .001). The MSH patients were less likely than the non-MSH patients to receive palliative care, regardless of race/ethnicity (12 692 [18.0%] vs 118 121 [22.3%]; P = .002). In an adjusted analysis, treatment at an MSH had a statistically significant association with lower odds of receiving palliative care (odds ratio, 0.67; 95% CI, 0.53-0.84). Conclusions and Relevance: Although the factors associated with minority patients' receipt of palliative care are complex, in this study, treatment at MSHs was associated with significantly lower odds of receiving any palliative care in an adjusted analysis, but black and Hispanic race/ethnicity was not. These findings suggest that the site of care is associated with race/ethnicity-based differences in palliative care.