Factors associated with clinical trial participation for patients with renal cell carcinoma.

OBJECTIVE: Recruitment of a diverse and representative study population is critical to the external validity of oncology clinical trials. The primary objective of this study was to characterize the factors associated with clinical trial participation for patients with renal cell carcinoma and the secondary objective was to examine differences in survival outcomes. MATERIALS AND METHODS: We used a matched case-control design by querying the National Cancer Database for patients with renal cell carcinoma who were coded as having enrolled in a clinical trial. Trial patients were matched in a 1:5 ratio to the control cohort based on clinical stage and then sociodemographic variables were compared between the 2 groups. Multivariable conditional logistic regression models evaluated factors associated with clinical trial participation. The trial patient cohort was then matched again in a 1:10 ratio based on age, clinical stage, and comorbidities. Log-rank test was used to compare overall survival (OS) between these groups. RESULTS: From 2004 to 2014, 681 patients enrolled in clinical trials were identified. Clinical trial patients were significantly younger and had a lower Charlson-Deyo comorbidity score. On multivariate analysis, male patients and white patients were more likely to participate compared to their Black counterparts. Having Medicaid or Medicare negatively associated with trial participation. Median OS was greater among clinical trial participants. CONCLUSION: Patient sociodemographic factors remain significantly associated with clinical trial participation and trial participants experienced superior OS to their matched counterparts.

The Impact of Venous Thromboembolism on Mortality and Morbidity During Nephrectomy for Renal Mass.

OBJECTIVE: To determine the morbidity, mortality, and costs associated with having concurrent venous thromboembolism (VTE) at the time of surgical resection of a renal mass. PATIENTS AND METHODS: We identified 108,430 patients undergoing elective partial or radical nephrectomy for a renal mass from 2013 to 2017 using the Premier Healthcare database. The association of VTE with 90-day complication rates, mortality, ICU admission, readmission, and direct hospital costs (2019 US dollars) was determined with multivariable logistic regression and quantile regression models, respectively. RESULTS: Of the 108,430 patients who underwent elective partial or radical nephrectomy, 1.2% (n = 1301) of patients were diagnosed with a preoperative VTE. Patients with preoperative VTE have higher rates of minor (odds ratio [OR] 1.47, 95% confidence inteval [CI] 1.34-1.62, P < .0001) and major complications (OR 2.53, 95% CI 2.23-2.86, P < .0001), mortality (OR 2.03, 95% CI 1.6-2.57, P < .0001), and readmissions (OR 1.73, 95% CI 1.57-1.90, P < .0001) compared to patients without preoperative VTE at the time of nephrectomy. Notably, the predicted probability for a major complication was significantly higher among patients with preoperative VTE who underwent either partial or radical nephrectomy, irrespective of the surgical approach utilized. Furthermore, rates of all types of complications except endocrine and soft tissue were significantly increased in patients undergoing nephrectomy with preoperative VTE compared to those without VTE. CONCLUSION: VTE at the time of nephrectomy is associated with significantly higher rates of major complications, increased mortality, and higher overall costs. Taken together, these findings have important implications for the counseling and management of renal masses in presence of VTE.

Impact of inflammatory bowel disease on radical prostatectomy outcomes and costs of care.

BACKGROUND: Recent studies suggest an association between prostate cancer and inflammatory bowel disease (IBD). Our objectives were to investigate clinical and financial impacts of IBD on radical prostatectomy (RP) and to determine the impact of surgical approach on our findings. METHODS: The Premier Hospital Database was queried for patients who underwent RP from 2003 to 2017. Multivariable logistic regression models were used to determine the independent impact of IBD on complications and readmission rates. We determined 90-day readmissions and examined 90-day hospital costs adjusted to 2019 US dollars with multivariable quantile regression models. RESULTS: Our study population included 262,189 men with prostate cancer, including 3,408 (1.3%) with IBD. There were higher odds for any complication for IBD patients compared with non-IBD controls for RP (15.64% vs. 10.66%). Patients with IBD had overall complication rates of 14.1% (P < 0.05) for open surgery and 17.2% for minimally invasive surgery (MIS) (P < 0.01). Between 2013 and 2017, the IBD cohort had significantly more complications (odds ratios (ORs): 2; 95% confidence interval (CI): 1.5 to 2.67; P < 0.0001), was more likely to have surgical costs in the top quartile (OR: 1.6; 95% CI: 1.23 to 2.1; P < 0.01), and had higher readmission rates (OR: 1.51; 95% CI: 1.1 to 2.06; P = 0.01). CONCLUSIONS: The IBD cohort who underwent MIS had the highest complication rates. Hospital readmissions and surgical costs were significantly higher for the IBD cohort who underwent RP between 2013 and 2017, when a minimally invasive approach was more prevalent than an open approach. These findings may be important when deciding which surgical approach to take when performing RP on men with IBD.

Genetic risk assessment for hereditary renal cell carcinoma: Clinical consensus statement.

BACKGROUND: Although renal cell carcinoma (RCC) is believed to have a strong hereditary component, there is a paucity of published guidelines for genetic risk assessment. A panel of experts was convened to gauge current opinions. METHODS: A North American multidisciplinary panel with expertise in hereditary RCC, including urologists, medical oncologists, clinical geneticists, genetic counselors, and patient advocates, was convened. Before the summit, a modified Delphi methodology was used to generate, review, and curate a set of consensus questions regarding RCC genetic risk assessment. Uniform consensus was defined as ≥85% agreement on particular questions. RESULTS: Thirty-three panelists, including urologists (n = 13), medical oncologists (n = 12), genetic counselors and clinical geneticists (n = 6), and patient advocates (n = 2), reviewed 53 curated consensus questions. Uniform consensus was achieved on 30 statements in specific areas that addressed for whom, what, when, and how genetic testing should be performed. Topics of consensus included the family history criteria, which should trigger further assessment, the need for risk assessment in those with bilateral or multifocal disease and/or specific histology, the utility of multigene panel testing, and acceptance of clinician-based counseling and testing by those who have experience with hereditary RCC. CONCLUSIONS: In the first ever consensus panel on RCC genetic risk assessment, 30 consensus statements were reached. Areas that require further research and discussion were also identified, with a second future meeting planned. This consensus statement may provide further guidance for clinicians when considering RCC genetic risk assessment. LAY SUMMARY: The contribution of germline genetics to the development of renal cell carcinoma (RCC) has long been recognized. However, there is a paucity of guidelines to define how and when genetic risk assessment should be performed for patients with known or suspected hereditary RCC. Without guidelines, clinicians struggle to define who requires further evaluation, when risk assessment or testing should be done, which genes should be considered, and how counseling and/or testing should be performed. To this end, a multidisciplinary panel of national experts was convened to gauge current opinion on genetic risk assessment in RCC and to enumerate a set of recommendations to guide clinicians when evaluating individuals with suspected hereditary kidney cancer.

Assessment of Prostate Cancer Treatment Among Black and White Patients During the COVID-19 Pandemic.

Importance: Early in the COVID-19 pandemic, racial/ethnic minority communities disproportionately experienced poor outcomes; however, the association of the pandemic with prostate cancer (PCa) care is unknown. Objective: To assess the association between race and PCa care delivery for Black and White patients during the first wave of the COVID-19 pandemic. Design, Setting, and Participants: This multicenter, regional, collaborative, retrospective cohort study compared prostatectomy rates between Black and White patients with untreated nonmetastatic PCa during the COVID-19 pandemic (269 patients from March 16 to May 15, 2020) and prior (378 patients from March 11 to May 10, 2019). Main Outcomes and Measures: Prostatectomy rates. Results: Of the 647 men with nonmetastatic PCa, 172 (26.6%) were non-Hispanic Black men, and 475 (73.4%) were non-Hispanic White men. Black men were significantly less likely to undergo prostatectomy during the pandemic compared with White patients (1 of 76 [1.3%] vs 50 of 193 [25.9%]; P < .001), despite similar COVID-19 risk factors, biopsy Gleason grade groups, and comparable prostatectomy rates prior to the pandemic (17 of 96 [17.7%] vs 54 of 282 [19.1%]; P = .75). Black men had higher median prostate-specific antigen levels prior to biopsy (8.8 ng/mL [interquartile range, 5.3-15.2 ng/mL] vs 7.2 ng/mL [interquartile range, 5.1-11.1 ng/mL]; P = .04). A linear combination of regression coefficients with an interaction term for year demonstrated an odds ratio for likelihood of surgery of 0.06 (95% CI, 0.01-0.35; P = .002) for Black patients and 1.41 (95% CI, 0.81-2.44; P = .23) for White patients during the pandemic compared with prior to the pandemic. Changes in surgical volume varied by site (from a 33% increase to complete shutdown), with sites that experienced the largest reduction in cancer surgery caring for a greater proportion of Black patients. Conclusions and Relevance: In this large multi-institutional regional collaborative cohort study, the odds of PCa surgery were lower among Black patients compared with White patients during the initial wave of the COVID-19 pandemic. Although localized PCa does not require immediate treatment, the lessons from this study suggest systemic inequities within health care and are likely applicable across medical specialties. Public health efforts are needed to fully recognize the unintended consequence of diversion of cancer resources to the COVID-19 pandemic to develop balanced mitigation strategies as viral rates continue to fluctuate.

Implications of the Revised Common Rule for Human Participant Research.

This paper looks at the implications of changes to the regulatory governance of human participant research that can be expected with implementation of the Revised Common Rule (RCR). The RCR refers to revisions of the existing federal regulations that govern the performance of research involving human subjects (ie, clinical research) in the United States and, under certain circumstances, when such research is also performed outside the United States. The term "common" is included because it refers to the fact that these regulations, often referred to as Code of Federal Regulations 46, is the common denominator regulations agreed to across a wide swath of federal agencies.

The Receipt of Industry Payments is Associated With Prescribing Promoted Alpha-blockers and Overactive Bladder Medications.

OBJECTIVE: To determine the impact of physicians' financial relationships with the pharmaceutical industry on prescribing marketed alpha-blockers and overactive bladder (OAB) medications. We also aim to examine if the number or total value of transactions is influential. MATERIALS AND METHODS: We linked the Open Payments Program database of industry payments to prescribers with Medicare Part D prescription data. We used binomial logistic regression to identify the association between receipt of industry payment and prescribing of marketed alpha-blockers (silodosin) and OAB medications (fesoterodine, solifenacin, and mirabegron). We also evaluated the impact of increasing total value and number of payments on prescribing of marketed drugs. RESULTS: The receipt of industry payment was associated with increased odds of prescribing the marketed drug for all included drugs: silodosin (odds ratio [OR] 34.1), fesoterodine (OR 5.9), solifenacin (OR 2.7), and mirabegron (OR 6.8) (all P <.001). We also found that increasing value of total payment and increasing frequency of payments were both independently associated with increased odds of prescribing with a dose-response effect. CONCLUSION: There is a consistent association between receipt of industry payment and prescribing marketed alpha-blockers and OAB medications. Both the total value and number of transactions were associated with prescribing.

Regional Cost Variations of Robot-Assisted Radical Prostatectomy Compared With Open Radical Prostatectomy.

INTRODUCTION: The purpose of the study was to evaluate the cost differences between robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP) in various census regions of the United States because RARP has been reported to be more expensive than ORP with significant regional cost variations in radical prostatectomy (RP) cost across the United States. PATIENTS AND METHODS: International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients with prostate cancer who underwent RARP or ORP from the Nationwide Inpatient Sample (NIS) database from 2009 to 2011. Hospital costs were compared using the Wilcoxon rank sum test and multivariable linear regression analysis adjusting for age, sex, race, comorbidities, and hospital characteristics. RESULTS: From the NIS database, 24,636 RARP and 13,590 ORP procedures were identified and evaluated. The lowest cost overall was in the South; the highest cost RARP was in the West and for ORP in the Northeast. In multivariable analysis, adjusted according to patient and hospital characteristics, RARP was 43.3% more costly in the Midwest, 37.2% more costly in the South, and 39.1% more costly in the West (P < .0001 for all). In contrast, the cost for RARP in the Northeast was 12.8% less than for ORP (P < .0001). CONCLUSION: Cost for RP significantly varies within the nation and in most regions it is significantly greater for RARP than for ORP. ORP in the Northeast is more costly than RARP. Further research is needed to delineate the reason for these differences and to optimize the cost of RP.

ERG and CHD1 heterogeneity in prostate cancer: use of confocal microscopy in assessment of microscopic foci.

BACKGROUND: Biomarkers predicting tumor response are important to emerging targeted therapeutics. Complimentary methods to assess and understand genetic changes and heterogeneity within only few cancer cells in tissue will be a valuable addition for assessment of tumors such as prostate cancer that often have insufficient tumor for next generation sequencing in a single biopsy core. METHODS: Using confocal microscopy to identify cell-to-cell relationships in situ, we studied the most common gene rearrangement in prostate cancer (TMPRSS2 and ERG) and the tumor suppressor CHD1 in 56 patients who underwent radical prostatectomy. RESULTS: Wild type ERG was found in 22 of 56 patients; ERG copy number was increased in 10/56, and ERG rearrangements confirmed in 24/56 patients. In 24 patients with ERG rearrangements, the mechanisms of rearrangement were heterogeneous, with deletion in 14/24, a split event in 7/24, and both deletions and split events in the same tumor focus in 3/24 patients. Overall, 14/45 (31.1%) of patients had CHD1 deletion, with the majority of patients with CHD1 deletions (13/14) correlating with ERG-rearrangement negative status (P < 0.001). CONCLUSIONS: These results demonstrate the ability of confocal microscopy and FISH to identify the cell-to-cell differences in common gene fusions such as TMPRSS2-ERG that may arise independently within the same tumor focus. These data support the need to study complimentary approaches to assess genetic changes that may stratify therapy based on predicted sensitivities.

Low Grade Micropapillary Urothelial Carcinoma, Does It Exist? - Analysis of Management and Outcomes from the Surveillance, Epidemiology and End Results (SEER) Database.

OBJECTIVE: To elucidate the oncologic behavior of Micropapillary Urothelial Bladder Carcinoma (MPBC), a rare aggressive variant histology. METHODS: All MPBC patients in SEER 17 database were compared with those with traditional urothelial carcinoma (UC). Kaplan-Meier curves were used to determine OS and CSS. A Cox proportional hazards model (CPH) was constructed to test the effect of covariates on outcomes. RESULTS: From 2001-2008, 120 MPBC patients were identified, 0.1% of all bladder cancer. MPBC presented with more high grade (86.1% vs. 38.7%, p<0.0001) and more high stage disease (40.8% NMI vs. 90.4% NMI, p < 0.0001) than UC. Low grade (LG) NMI MPBC had worse OS and CSS compared to LG UC (p=0.0037, p<0.0001 respectively), and did no better than high grade (HG) NMI MPBC. No difference was detected between HG NMI MPBC and HG NMI UC pts. A CPH model controlling for stage, grade, treatment, age, race, and sex detected no significant survival difference in MPBC vs. UC (HR 1.04, p=0.7966). For NMI MPBC (n=49), only 4 patients underwent definitive therapy, of whom none died of disease. However, in those not receiving definitive therapy (n=45), 7 cancer specific deaths occurred (15.6%). CONCLUSION: Controlling for stage and grade, no survival difference could be detected between MPBC and UC. Low grade NMI MPBC behaved similarly to both high grade MPBC and high grade UC. We propose that all MPBC (regardless of grade) be managed as high grade disease, and that strong consideration for definitive therapy should be given in all cases.

Outcomes of laparoscopic partial nephrectomy after fellowship training.

BACKGROUND AND OBJECTIVES: Experienced surgeons at select high-volume centers have reported favorable outcomes of laparoscopic partial nephrectomy (LPN) in their contemporary experience. However, it is unclear whether recently fellowship-trained surgeons can replicate such outcomes. We evaluated LPNs performed by 3 surgeons in their initial years of independent practice following laparoscopic fellowship training. METHODS: Prospectively maintained databases were queried for LPNs performed during the first 3.5 years of practice. Intraoperative parameters, oncological efficacy, and postoperative complications were analyzed. RESULTS: Of 138 total LPNs (76 left, 62 right), the mean patient age was 57 years, mean tumor size was 2.52cm, and mean depth of invasion was 1.68cm. Mean OR time was 252 minutes, mean warm ischemia time (WIT) was 26 minutes, and mean estimated blood loss (EBL) was 202 mL. Complications occurred in 7 patients (5%), and conversions occurred in 9 patients (7%). Comparison of the first 15 vs. the last 15 cases demonstrated a significant reduction in mean OR time (204 min vs. 253 min, P=0.007), and mean WIT (24 min vs. 32 min, P<0.001). No significant change was demonstrated for tumor size (2.6 cm vs. 2.4 cm, P=0.390) or EBL (226 mL vs. 220 mL, P=0.922). CONCLUSION: Newly fellowship-trained surgeons performing LPN achieve initial outcomes comparable to those reported by highly experienced surgeons. Further experience reduced total operative and warm ischemia times.

Healthcare economics of bladder cancer: cost-enhancing and cost-reducing factors.

PURPOSE OF REVIEW: The diagnosis and treatment of bladder cancer represents a significant financial burden to the population in the United States. Therapeutic advances in bladder cancer care have come at a high cost to payers, providers, and patients. This study describes the principals of cost-effectiveness evaluation in healthcare and provides recommendations for a more economical use of resources in bladder cancer care. RECENT FINDINGS: Although several studies have demonstrated that bladder cancer is a common disease associated with substantial economic burden for patients and society, the evidence supporting the cost-effectiveness of many interventions in bladder cancer care is limited and of insufficient quality. In addition, very little is known about quality of life, the preferred outcome measure for economic evaluations, associated with bladder cancer states and treatments. Moreover, current clinical guidelines for bladder cancer care do not incorporate economic factors when evaluating clinical pathways. SUMMARY: Although cost-effectiveness studies in bladder cancer could allow us to know how healthcare dollars are being spent and assist in determining more effective ways to allocate resources, most of the currently used interventions have not undergone economic assessment.