The Prevalence and Impact of Urinary Marker Testing in Patients with Bladder Cancer.

PURPOSE: Novel urinary tumor markers for bladder cancer may permit early detection and improved oncologic outcomes but data on use is limited. We sought to identify trends in the application of urinary markers and long-term outcomes of urinary tumor marker use in patients with bladder cancer. MATERIALS AND METHODS: Data from the SEER (Surveillance, Epidemiology and End Results)-Medicare database from 2001 to 2011 were used to identify a cohort of 64,450 patients with bladder cancer who underwent urinary marker testing with UroVysion® fluorescence in situ hybridization, or the NMP22® or BTA Stat® test. We assessed the prevalence of urinary marker testing and urine cytology. Characteristics of patients who did and did not undergo urinary marker testing were analyzed by the chi-square test. Urinary marker testing predictors were analyzed with a multivariable logistic regression model and Cox proportional hazards were used to determine unadjusted cancer specific and overall mortality risks. RESULTS: The rate of urinary marker testing increased from 17.8% to a peak of 28.2% during the study years (p <0.0001). Predictors of marker use included female gender, younger age and lower Charlson score. Overall and cancer specific survival improved on Kaplan-Meier and Cox proportional hazards analyses with urinary marker testing. CONCLUSIONS: Increased urinary marker testing was documented over all stages and grades of bladder cancer, and in certain patient and provider variables. This increase may have contributed to improved overall and cancer specific survival. Additional investigation is necessary to further characterize this benefit.

Racial Disparities in Active Surveillance for Prostate Cancer.

PURPOSE: Active surveillance protocols track low risk prostate cancer progression over time. However, given the lack of uniform criteria for managing low risk prostate cancer, men who qualify for active surveillance might have less intensive surveillance and, thus, experience poorer outcomes. In this study we examined racial disparities in the frequency and intensity of active surveillance between African-American and Caucasian men. MATERIALS AND METHODS: Using the linked SEER-Medicare data set we identified 13,374 men with low risk prostate cancer (defined by the D'Amico criteria) diagnosed from 2004 to 2009 and then followed through 2011. A total of 2,916 men did not receive any treatment (radiation, hormonal therapy or surgery) within 1 year after diagnosis. Men were considered to be on active surveillance if they had at least 1 of the following 3 surveillance strategies within 2 years after diagnosis, namely 1 or more prostate biopsies, 4 or more prostate specific antigen tests, and/or 4 or more visits to the doctor with prostate cancer listed as the diagnosis. To compare the frequency of active surveillance between the groups (African-American vs Caucasian) we used the chi-square test. To estimate the odds ratio of active surveillance we used multivariable logistic regression after adjusting for possible confounders such as year of diagnosis, age at diagnosis, socioeconomic status and Charlson score. RESULTS: Of the 2,916 untreated men 1,141 (39%), including 963 (37%) Caucasian men and 178 (58%) African-American men (p <0.0001), did not undergo any of the 3 surveillance strategies but instead were essentially on watchful waiting. Caucasian men (vs African-American) were more likely to be on active surveillance, with 1,646 (63.1%) vs 129 (42.0%) opting for 1 surveillance strategy (p <0.0001), 783 (30.0%) vs 50 (16.3%) opting for any 2 strategies (p <0.0001) and 193 (7.4%) vs 11 (3.6%) going through all 3 (p=0.01). On multivariable analysis African-American men had significantly lower odds of being on active surveillance than Caucasian men (OR 0.52, 95% CI 0.40-0.67). Men with more comorbidities (Charlson score 1 or greater) had significantly higher odds of being placed on active surveillance than watchful waiting (OR 1.7, 95% CI 1.46-2.12). CONCLUSIONS: Among those not treated for low risk prostate cancer, Caucasian men were placed on active surveillance more frequently than African-American men, who often defaulted to de facto watchful waiting after an initial period of active surveillance. This discrepancy raises questions about the factors favoring watchful waiting over active surveillance. Moreover, given the lack of consensus regarding the most efficient active surveillance strategy, we anticipate that racial disparities in the use of active surveillance will persist, especially in African-American patients.

Impact of initial local therapy on survival in men later receiving chemotherapy for prostate cancer: a population-based, propensity-weighted multivariable analysis.

PURPOSE: Prostate cancer remains a common disease that is frequently treated with multimodal therapy. The goal of this study was to assess the impact of treatment of the primary tumor on survival in men who go onto receive chemotherapy for prostate cancer. METHODS: Using surveillance, epidemiology and end results (SEER)-Medicare data from 1992 to 2009, we identified a cohort of 1614 men who received chemotherapy for prostate cancer. Primary outcomes were prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). We compared survival among men who had previously undergone radical prostatectomy (RP), radiation therapy (RT), or neither of these therapies. Propensity score adjusted Cox proportional hazard models and weighted Kaplan-Meier curves were used to assess survival. RESULTS: Compared to men who received no local treatment, PCSM was lower for men who received RP ± RT (HR 0.65, p < 0.01) and for those who received RT only (HR 0.79, p < 0.05). Patients receiving neither RP nor RT demonstrated higher PCSM and ACM than those receiving treatment in a weighted time-to-event analysis. Men who received RP + RT had longer mean time from diagnosis to initiation of chemotherapy (100.7 ± 47.7 months) than men with no local treatment (48.8 ± 35.0 months, p < 0.05). CONCLUSION: In patients who go on to receive chemotherapy, treatment of the primary tumor for prostate cancer appears to confer a survival advantage over those who do not receive primary treatment. These data suggest continued importance for local treatment of prostate cancer, even in patients at high risk of failing local therapy.

Risk of end stage kidney disease after radical cystectomy according to urinary diversion type.

PURPOSE: The risk of renal insufficiency has historically been viewed as a long-term consequence of urinary diversion after radical cystectomy. However, there are little data on the long-term rate of end stage kidney disease after urinary diversion and few studies have compared end stage kidney disease rates by diversion type. In a large, population based cohort we evaluated the risk of end stage kidney disease in patients who received an ileal conduit vs continent urinary diversion after cystectomy for bladder cancer. MATERIALS AND METHODS: Using the SEER-Medicare 1992 to 2010 data set we identified 4,015 patients treated with radical cystectomy for bladder cancer, excluding those with preexisting renal disease or clinically significant preoperative hydronephrosis. The outcome of interest was end stage kidney disease stratified by diversion type. We used a Cox proportional hazard model for multivariate analysis controlling for demographic, tumor and comorbidity characteristics. RESULTS: End stage kidney disease developed in 7.2% of patients, including 84% with an ileal conduit and 16% with continent urinary diversion. Median followup was 34 months (IQR 12-73). On multivariate analysis no increased risk of end stage kidney disease was associated with continent diversion (HR 1.06, 95% CI 0.78-1.44, p = 0.71). Overall the estimated risk at 5, 10 and 15 years was 8.3% (95% CI 7.1-9.5), 16.9% (95% 14.6-19.2) and 24.4% (95% CI 20.3-28.5), respectively. CONCLUSIONS: No significant difference in the rate of end stage kidney disease was identified when comparing ileal conduits to continent urinary diversion. A significant risk of end stage kidney disease in the long term was identified in patients with post-cystectomy survival beyond 5 years.

Factors associated with the Journal Impact Factor (JIF) for Urology and Nephrology Journals.

PURPOSE: The Journal Impact Factor (JIF) is an index used to compare a journal's quality among academic journals and it is commonly used as a proxy for journal quality. We sought to examine the JIF in order to elucidate the main predictors of the index while generating awareness among scientific community regarding need to modify the index calculation in the attempt to turn it more accurate. MATERIALS AND METHODS: Under the Urology and Nephrology category in the Journal Citations Report Website, the top 17 Journals by JIF in 2011 were chosen for the study. All manuscripts' abstracts published from 2009-2010 were reviewed; each article was categorized based on its research design (Retrospective, Review, etc). T and correlation tests were performed for categorical and continuous variables respectively. The JIF was the dependent variable. All variables were then included in a multivariate model. RESULTS: 23,012 articles from seventeen journals were evaluated with a median of 1,048 (range=78-6,342) articles per journal. Journals with a society affiliation were associated with a higher JIF (p=0.05). Self-citations (rho=0.57, p=0.02), citations for citable articles (rho=0.73,p=0.001), citations to non-citable articles (rho=0.65,p=0.0046), and retrospective studies (rho=-0.51,p=0.03) showed a strong correlation. Slight modifications to include the non-citable articles in the denominator yield drastic changes in the JIF and the ranking of the journals. CONCLUSION: The JIF appears to be closely associated with the number of citable articles published. A change in the formula for calculating JIF to include all types of published articles in the denominator would result in a more accurate representation.

Work Productivity and General Health Through 2 Years of Guselkumab Treatment in a Phase 3 Randomized Trial of Patients With Active Psoriatic Arthritis.

INTRODUCTION: To evaluate the effect of guselkumab on work productivity and nonwork daily activity impairment and general health status through 2 years in patients who were biologic-naïve with active psoriatic arthritis (PsA) in the phase 3 DISCOVER-2 clinical trial. METHODS: Adult patients with PsA were randomized to subcutaneous injections of guselkumab 100 mg every 4 weeks (Q4W); at weeks 0, 4, then every 8 weeks (Q8W); or placebo (through week 24 with crossover to guselkumab Q4W). Work productivity and nonwork daily activity impairment were assessed using the Work Productivity and Activity Impairment Questionnaire for PsA (WPAI-PsA) and patient-reported general health status using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index and EQ-Visual Analog Scale (EQ-VAS). Least-squares (LS) mean changes from baseline in WPAI-PsA domains and EQ-5D-5L/EQ-VAS were assessed through week 100. Changes in employment status were utilized to estimate potential indirect savings from improved work productivity. RESULTS: Of 739 randomized patients, 738 had available baseline data for the analyses (Q4W 245; Q8W 248; placebo 245). At week 24, greater improvements in work productivity, nonwork daily activity, and EQ-5D-5L/EQ-VAS were observed in the Q4W and Q8W groups versus the placebo group. At week 100, LS mean reductions in work productivity impairment (- 23.8% to - 28.0%) and nonwork daily activity impairment (- 26.6% to - 29.2%) and improvements in EQ-5D-5L/EQ-VAS (0.14 to 0.15/21.2 to 25.0) were maintained in patients receiving guselkumab. Among patients employed at baseline, 12.1-16.4% were not employed at week 100, and 20.0-25.3% shifted from not employed at baseline to employed at week 100. Potential yearly indirect cost savings (USD) from improved work productivity at week 100 ranged from $16,529 to $19,409. CONCLUSION: Patients with active PsA treated with guselkumab demonstrated reduced impairment in work productivity and nonwork daily activity, together with improvement in general health status and substantial potential cost savings, over a 2-year period. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03158285.

Society for fetal urology recommendations for postnatal evaluation of prenatal hydronephrosis--will fewer voiding cystourethrograms lead to more urinary tract infections?

PURPOSE: There is no consensus on the extent and mode of postnatal imaging after a diagnosis of prenatal hydronephrosis. We validated the protocol of our practice, which parallels current Society for Fetal Urology (SFU) recommendations, in limiting voiding cystourethrogram, while examining its impact on the incidence of febrile urinary tract infections. A secondary goal was to examine predictors of postnatal intervention. MATERIALS AND METHODS: We evaluated a cohort of 117 infants with prenatal hydronephrosis and retrospectively reviewed outcomes. Excluded from study were 30 infants with anatomical abnormalities. Third trimester prenatal ultrasound was done to evaluate SFU grade, laterality and anteroposterior diameter. Cox proportional hazard model and chi-square analysis were used to assess predictors of resolution and surgical intervention. RESULTS: A total of 87 infants with a median followup of 33.5 months were included in analysis. Postnatal voiding cystourethrogram was done in 52 patients, of whom 7 had vesicoureteral reflux. In 6 infants (6.9%) a febrile urinary tract infection developed, which was diagnosed with a catheter specimen during followup. In 3 infants a urinary tract infection developed immediately after catheterization. Anteroposterior diameter 9 mm or greater and SFU grade 3 or greater independently predicted the need for postnatal intervention (p = 0.0014 and 0.001, respectively). CONCLUSIONS: With adherence to our protocol, voiding cystourethrogram was avoided in almost half of evaluated infants. No infant diagnosed with vesicoureteral reflux had a urinary tract infection. Catheterization was associated with a urinary tract infection in 50% of cases. An anteroposterior diameter of 9 mm or greater and a SFU grade of 3 or greater were associated with postnatal progression to surgery. Patients with a SFU grade of 4 progressed to surgical intervention at a faster rate than those with a grade of greater than 3.

Evaluation of use of stage of tobacco epidemic to predict post-immigration smoking behaviors.

INTRODUCTION: This research uses the Lopez stage of tobacco epidemic model to evaluate post-immigration smoking behavior. Stage is a composite measure of tobacco norms of a country: smoking prevalence, cigarette consumption, and tobacco-related morbidity. The Lopez model characterizes the changing relationship between smoking prevalence and tobacco-related mortality and morbidity as a country progresses through the 4 successive stages of the tobacco epidemic. METHODS: Survey data from Southeast Asian and Latino immigrants (from stage 1 and stage 2 countries) (n = 2,076) were used to evaluate stage of tobacco epidemic of country of emigration. Stage was compared with standard acculturation measures and community identification measures to understand post-immigration smoking behavior in the United States. Comparative analysis by stage and gender includes bivariate associations and logistic regression models to predict post-immigration smoking behavior. RESULTS: Males:Pre-immigration prevalence and consumption rates of our study sample conform to prevalence and consumption of stage 1 and stage 2 countries predicted by the Lopez model. Post-immigration smoking uptake is equivalent to pre-immigration uptake for stage 1 males. The uptake rate for stage 2 males post-immigration is significantly lower (22.1%) than pre-immigration uptake (41.4%). Stage is a statistically significant predictor of post-immigration smoking uptake (OR = 3.08, CI = 1.82-5.22, p < .01). Females:Stage of country of birth is not significantly predictive of post-migration smoking uptake. CONCLUSIONS: The finding of stage to be a strong predictor of post-immigration smoking behavior among males provides a promising measurement tool. Prevalence and consumption of females in our study sample support the need for revisions to the stage model.

Racial disparities in nephrectomy and mortality among patients with renal cell carcinoma: Findings from SEER.

PURPOSE: To assess racial differences in the receipt of nephrectomy in patients diagnosed RCC in the US. MATERIALS AND METHODS: 2005 to 2015 data from the SEER database was analyzed and 70,059 patients with RCC were identified. We compared demographic and tumor characteristics between black patients and white patients. We applied logistic regression to assess the association between race and the odds of the receipt of nephrectomy. We also applied Cox proportional hazards model to assess the impact of race on cancer-specific mortality (CSM) and all-cause mortality (ACM) in patients diagnosed with RCC in the US. RESULTS: Black patients had 18% lower odds of receiving nephrectomy compared to white patients (p < 0.0001). The odds of the receipt of nephrectomy also reduced with age at diagnosis. In addition, patients with T3 stage had the greatest odds of receiving nephrectomy when compared to T1 (p < 0.0001). There was no difference in the risk of cancer-specific mortality between black patients and white patients; black patients had 27% greater odds of all-cause mortality than white patients (p < 0.0001). Patients who did not receive nephrectomy had a 42% and 35% higher risk of CSM and ACM respectively, when compared to patients who received nephrectomy. CONCLUSIONS: Black patients diagnosed with RCC in the US have a greater ACM risk and are less likely than white patients to receive nephrectomy. Systemic changes are needed to eliminate racial disparity in the treatment and outcomes of RCC in the US.

Intensity modulated radiation therapy replaces 3-dimensional conformal radiotherapy as prostate cancer treatment.

PURPOSE: We describe trends in the use of intensity modulated radiotherapy vs 3-dimensional conformal radiotherapy for prostate cancer and identified predictors of intensity modulated radiotherapy use. MATERIALS AND METHODS: From the SEER (Surveillance, Epidemiology and End Results)-Medicare database we identified 52,290 men with incident nonmetastatic prostate cancer from 2000 to 2007 who were treated with radiotherapy. We tracked trends in the use of intensity modulated radiotherapy, 3-dimensional conformal radiotherapy, brachytherapy and combinations. Patient demographic and clinical characteristics were described and compared using chi-square and multivariate logistic regression. Trends at the place of service were also examined. RESULTS: Intensity modulated radiotherapy use increased from 1% of all radiotherapy in 2000 to 70% in 2007. Three-dimensional conformal radiotherapy use decreased from 75% to 12%. Most cases were treated with intensity modulated radiotherapy monotherapy. In 2007, 12% of the cohort received intensity modulated radiotherapy plus brachytherapy. In 2005, 81% of all external radiation was given as intensity modulated radiotherapy. Except for geography there were minimal differences in patient demographic and clinical characteristics between those treated with 3-dimensional conformal radiotherapy vs intensity modulated radiotherapy. On multivariate analysis significant predictors of the odds of receiving intensity modulated radiotherapy vs 3-dimensional conformal radiotherapy were low Gleason score, high education, white or Asian race and urban place of residence. The odds of receiving intensity modulated radiotherapy varied greatly by registry. A lesser part of the growth in intensity modulated radiotherapy use occurred at freestanding facilities. CONCLUSIONS: Intensity modulated radiotherapy has replaced 3-dimensional conformal radiotherapy as the primary form of external radiation for prostate cancer. The choice of intensity modulated radiotherapy over 3-dimensional conformal radiotherapy is not related to common clinical factors such as age, comorbidities or tumor aggressiveness. Although geographic variations exist, by 2007 intensity modulated radiotherapy dominated in all regions studied.

Bias due to missing SEER data in D'Amico risk stratification of prostate cancer.

PURPOSE: We examined the degree of exclusion bias that may occur due to missing data when grouping prostate cancer cases from the SEER (Surveillance, Epidemiology and End Results) database into D'Amico clinical risk groups. Exclusion bias may occur since D'Amico staging requires all 3 variables to be known and data may not be missing at random. MATERIALS AND METHODS: From the SEER database we identified 132,606 men with incident prostate cancer from 2004 to 2006. We documented age, race, Gleason score, clinical T stage, PSA and geographic region. Men were categorized into D'Amico risk groups. Those with 1 or more unknown tumor variables (prostate specific antigen, T stage and/or Gleason score) were labeled unclassified. We compared the value of the other 2 known clinical variables for men with known vs unknown prostate specific antigen, Gleason score and T stage. Demographics were compared for those with and without missing data. Results were compared using chi-square and logistic regression. RESULTS: Of the men 33% had 1 or more unknown tumor variables with T stage the most commonly missing variable. There was no clinically significant difference in the value of the other 2 known tumor variables when T stage or prostate specific antigen was missing. Men older than 75 years were more likely to have unknown variables than younger men. There was significant geographic variation in the frequency of unclassified D'Amico data. CONCLUSIONS: In studies in which the data set is limited to men who can be classified into a D'Amico risk group 33% of eligible patients are excluded from analysis. Such men are older and from certain SEER registries but they have tumor characteristics similar to those with complete data.

Influence of Histologic Types and Subtypes on Survival Outcomes of Intermediate-High and High-Risk Renal Cell Carcinoma Following Nephrectomy: Findings From the SEER Database.

OBJECTIVE: To understand the influence of histologic subtypes on the survival outcomes of intermediate-high and high-risk renal cell carcinoma (RCC) following nephrectomy. METHODS: This study employed data files from the SEER Program to identify patients diagnosed with intermediate-high or high risk RCC and treated with nephrectomy. Unadjusted Kaplan Meier curves, and multivariable Cox regression analyses were applied to estimate the hazards of histologic types for overall survival (OS) and cancer-specific survival (CSS). RESULTS: OS was higher for chromophobe (HR=0.58, 95% CI 0.47-0.70; P<.0001), similar for papillary (HR=0.90, 95% CI 0.80-1.02; P=.11) and worse for sarcomatoid (HR=3.17, 95% CI 2.70-3.72; P<.0001) subtypes relative to the clear cell subtype. OS was lower in the high-risk disease (HR=2.35, 95% CI 2.01-2.74; P <.0001) versus intermediate-high risk disease. CSS was higher for chromophobe (HR=0.47, 95% CI 0.35-0.63; P<.0001), similar for papillary (HR=0.91, 95% CI 0.77-1.08; P=.28) and worse for sarcomatoid (HR=4.19, 95% CI 3.50-5.02; P<.0001) subtypes relative to the clear cell subtype. CSS was lower for the high-risk disease (HR=2.86, 95%CI 2.39-3.43; P <.0001) relative to intermediate-high risk disease.

Clinical and economic burdens of recurrence following nephrectomy for intermediate high- or high-risk renal cell carcinoma: A retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data.

BACKGROUND: Renal cell carcinoma (RCC) is associated with a high risk of recurrence. Although RCC has been shown to impose a substantial burden on patients, little is known about the incremental clinical and economic burden attributable to disease recurrence. With recent advances in the RCC-therapeutic landscape, including adjuvant therapies, it is important to quantify the clinical and economic burden associated with RCC recurrence to better evaluate the potential impact of treatment in this patient population. OBJECTIVE: To quantify the incremental clinical and economic burden associated with disease recurrence among patients with intermediate high-risk and high-risk RCC postnephrectomy. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare database (2007-2016) were used to identify patients with newly diagnosed, intermediate high-risk or high-risk RCC following nephrectomy. Patients with a diagnosis of metastatic disease or repeat nephrectomy or initiating a systemic treatment for advanced RCC were grouped as the recurrence cohort; patients without evidence of recurrence were grouped as the cohort without recurrence. Health care resource utilization (HRU), health care costs (2019 US dollars), and overall survival (OS) were compared between cohorts with and without recurrence, adjusting for demographic and clinical characteristics. RESULTS: A total of 269 patients with recurrence and 374 patients without recurrence were analyzed. Mean age was 75.2 and 75.7 years (P = 0.383), respectively, and 64.7% and 57.8% (P = 0.076) of patients were male, respectively. Median follow-up duration was 17 and 28 months, respectively. Patients with recurrence had a significantly shorter OS relative to patients without recurrence (adjusted hazard ratio = 6.00; 95% CI = 4.24-8.48; P < 0.001). Additionally, compared with patients without recurrence, patients with recurrence had significantly more inpatient admissions (0.16 vs 0.04 admissions per person-month [PM]; adjusted incidence rate ratio [aIRR] = 3.88; 95% CI = 3.12-4.81), outpatient visits (3.06 vs 1.77 visits per PM; aIRR = 1.68; 95% CI = 1.56-1.81), emergency department visits (0.10 vs 0.05 visits per PM; aIRR = 2.11; 95% CI = 1.66-2.68), and days hospitalized (1.40 vs 0.35 days per PM; aIRR = 6.73; 95% CI = 4.95-9.15) per patient per month (all P < 0.001). Adjusted mean monthly health care costs per patient were significantly higher among patients with recurrence vs patients without recurrence (differences of all-cause total costs, total medical costs, and pharmacy cost per month: $6,320, $4,924, and $1,387; all P < 0.001). CONCLUSIONS: RCC recurrence is associated with a significant increase in mortality, HRU, and health care costs, highlighting the substantial unmet need in patients with intermediate high-risk and high-risk RCC postnephrectomy when adjuvant therapies are not widely available. DISCLOSURES: Dr Sundaram is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., and holds stock in AbbVie, Abbott, Johnson & Johnson, Bristol Myers Squibb, and Merck & Co., Inc. Dr Bhattacharya is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., and holds stock in Merck & Co., Inc. Dr Adejoro and Dr Rogerio were employees of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc. at the time of study conduct. Dr Adejoro holds stock in Johnson & Johnson. Dr Song, Dr Zhang, Mr Carley, and Dr Signorovitch are employees of Analysis Group, Inc., a consulting firm that received funding from Merck & Co., Inc. for the conduct of this research. Ms Zhu was an employee of Analysis Group, Inc. at the time of study conduct. Dr Haas is a Professor of Medicine at the Perelman School of Medicine, University of Pennsylvania and also serves on the advisory board for Aveo, Calithera and Exelixis, Co. Financial support for this study was provided by Merck & Co., Inc. The study sponsor was involved in the design and conduct of the study; collection, management, analysis, interpretation of data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Association between preoperative prostate-specific antigen levels and mortality in high- and intermediate-grade prostate cancer patients who received radical prostatectomy: Findings from the SEER database.

BACKGROUND: The degree of expression of prostate-specific antigen (PSA) has been applied for the purpose of screening and monitoring the progression of prostate cancer. The goal of this study was to evaluate the association between preoperative PSA levels and mortality outcomes in men with high- and intermediate-grade prostate cancer who received radical prostatectomy. METHODS: The 2004-2014 files of the Surveillance, Epidemiology, and End Result database were analyzed. A total of 97,357 patients with non-metastatic high- and intermediate-grade adenocarcinoma of the prostate who received radical prostatectomy were identified. Using Kaplan-Meier estimates and multivariable Cox proportional hazard models, the relationship between preoperative PSA values and cancer-specific mortality outcomes in men with high- and intermediate-grade prostate cancer who received radical prostatectomy was tested. RESULTS: Of 97,357 patients with high- and intermediate-grade prostate cancer who received radical prostatectomy from 2001 to 2014, there were 983 cancer-specific deaths, and the average follow-up time for the cohort was 85.0 (34.6) months. Preoperative PSA values > 10 ng/ml were associated with greater risk of cancer-specific mortality (hazard ratio 2.3, P < 0.0001) when compared to the referent/normal values for preoperative PSA (<4 ng/ml). Individuals with preoperative PSA values 4-10 ng/ml had lower risk of prostate cancer-specific mortality (hazard ratio 0.80, P = 0.03) when compared to individuals with normal preoperative PSA values. CONCLUSIONS: Individuals with preoperative PSA values 4-10 ng/ml had 20% lower risk of prostate cancer-specific mortality when compared to individuals with preoperative PSA values of <4 ng/dl. The findings from this study suggest that low or normal preoperative PSA values may not always mean that prostate cancer is indolent, and more work needs to be done to better classify risk in men with prostate cancer.

Cost-effectiveness of pembrolizumab with axitinib as first-line treatment for advanced renal cell carcinoma.

OBJECTIVE: Pembrolizumab/axitinib significantly prolonged overall survival (OS) and progression-free survival (PFS), and increased objective response rate versus sunitinib in the phase III trial KEYNOTE-426 among previously untreated patients with advanced renal cell carcinoma (RCC). This study assessed the cost-effectiveness of pembrolizumab/axitinib versus other first-line treatments of advanced RCC from a US public healthcare payer perspective. METHODS: A partitioned survival model with three states (progression-free, progressed, death) evaluated lifetime costs and quality-adjusted life-years (QALYs) for pembrolizumab/axitinib and other first-line regimens: sunitinib, pazopanib and avelumab/axitinib in the overall population; and sunitinib, cabozantinib and nivolumab/ipilimumab in the subgroup with intermediate/poor prognostic risk. Costs of treatments, adverse events and medical resources were estimated. OS, PFS and treatment duration were extrapolated using parametric models fitted to KEYNOTE-426 data and hazard ratios from network meta-analyses. Utilities were derived through mixed-effects regressions of KEYNOTE-426 EuroQol-5 Dimensions-3 Levels data. RESULTS: In the overall population, pembrolizumab/axitinib was associated with incremental cost-effectiveness ratios (ICERs) of $95,725/QALY versus sunitinib and $128,210/QALY versus pazopanib, and was dominant (lower cost, higher effectiveness) versus avelumab/axitinib, with incremental QALY gains of 2.73, 2.40 and 1.80 versus these therapies, respectively. In the intermediate/poor-risk subgroup, base-case ICERs for pembrolizumab/axitinib were $101,030/QALY versus sunitinib, $6989/QALY versus cabozantinib, and $130,934/QALY versus nivolumab/ipilimumab, with incremental QALY gains of 2.62, 1.78 and 1.06 versus these therapies. CONCLUSIONS: In this economic evaluation, pembrolizumab/axitinib was associated with higher life expectancy and QALYs and, based on typical willingness-to-pay thresholds of $150,000-$180,000/QALY, was found cost-effective versus other first-line treatments for advanced RCC in the US.

Racial Disparities in the Presentation, Early Definitive Surgical Treatment, and Mortality Among Men Diagnosed with Poorly Differentiated/Undifferentiated Non-metastatic Prostate Cancer in the USA.

OBJECTIVE: To assess the influence of race on presentation of poorly differentiated/undifferentiated prostate cancer, use of radical prostatectomy (RP) as primary treatment and survival outcomes. METHODS: Using the 2004-2014 files of the Surveillance, Epidemiology, and End Results (SEER) data, we identified 244,167 black and white men diagnosed with poorly differentiated/undifferentiated prostate cancer. Demographic and tumor characteristics of study patients were compared by race. Logistic regression was used to evaluate the influence of race on receipt of RP. Cox proportional hazard models were fitted to determine the impact of RP and race on cancer-specific mortality (CSM) and all-cause mortality (ACM). RESULTS: Compared to white men, black men were diagnosed of prostate cancer at a younger age (64.2 years versus (vs) 67.5 years, p < 0.0001) and presented with higher median prostate-specific antigen, PSA (24.4 ng/ml vs 22.1 ng/ml, p < 0.0001) but lower disease stage. Lower proportion of black men received RP compared to white men (33.9% vs 42.6%; p < 0.0001). The odds of receipt of RP were 2 times higher in white men relative to black men. The risks of CSM and ACM were over 2 times and 3 times respectively higher in patients who did not receive RP vs patients who received RP in the study population and in each race. CONCLUSION: Despite the younger age at diagnosis of poorly differentiated/undifferentiated prostate cancer and higher PSA at diagnosis in black men, white men had significantly higher odds of receipt of RP relative to black men.

Real-World Treatment Patterns Among Patients Initiating Small Molecule Kinase Inhibitor Therapies for Thyroid Cancer in the United States.

INTRODUCTION: Little is known about real-world use of small molecule kinase inhibitors (SMKI) for advanced thyroid cancer in the United States. This study examined prescribing patterns of SMKI agents recommended by the National Comprehensive Cancer Center (NCCN). METHODS: This retrospective study used a national health insurance database to identify patients diagnosed with thyroid cancer during 1/1/2006-6/30/2016 and with prescription claims for NCCN-recommended SMKI during 1/1/2010-5/31/2016 whose first claim date was the index date. Inclusion also required continuous enrollment in a health plan for 3 months pre-index (baseline) and ≥ 1 month post-index (follow-up) with no claims for SMKI during baseline. Lines of therapy (LOT) were defined by the date of SMKI claims and days of drug supply. Median time to SMKI discontinuation in each LOT was estimated by Kaplan-Meier method. RESULTS: The study included 217 patients. During follow-up (mean duration 499.0 days), 35.5% of patients (n = 77) received a second or later LOT; among patients with ≥ 12 months follow-up after first LOT (LOT1) initiation, 53.1% (n = 60) received a second or later LOT. Median treatment duration was 5.0 months for LOT1 and 5.1 months for LOT2. Over the entire follow-up period (2010-2016), sorafenib was the most common regimen in LOT1 (36.9% of patients) and LOT2 (24.7%) followed by sunitinib and levantinib (13.4% each) in LOT1 and sunitinib (19.5%) in LOT2. Starting in 2015, the year lenvatinib was approved for differentiated thyroid cancer, lenvatinib was the most common first-line regimen among patients initiating LOT1 in 2015 (43.4%) and 2016 (66.7%). CONCLUSION: Sorafenib was the most common first-line agent during 2010-2014 but was supplanted by lenvatinib starting in 2015. Approximately 36-53% of patients received a second-line treatment. Median treatment duration results suggested potential benefit of SMKI in second-line therapy. SMKI treatment after first-line failure may be considered for appropriately selected patients. FUNDING: Eisai, Inc. (Woodcliff Lake, NJ).

Treatment patterns of biologics in US patients with ankylosing spondylitis: descriptive analyses from a claims database.

AIM: Examine treatment patterns among patients with active ankylosing spondylitis (AS) treated with a TNF inhibitor (TNFi). PATIENTS & METHODS: Patients with AS who initiated a TNFi between 1 January 2013, and 31 January 2015, were identified in the Optum Research Database. Outcomes included adherence, persistence, discontinuation and therapy modifications of the index TNFi during 12-month follow-up. RESULTS: Of the 426 patients included, 40.6% persisted on the index TNFi for ≥12 months, 31.0% discontinued, 21.4% switched to a different TNFi, and 7.0% discontinued and then restarted. Of the 333 patients who persisted on their TNFi for >90 days, 44.7% received ≥1 add-on medication. CONCLUSION: A high proportion of patients with AS switched, discontinued or modified their TNFi therapy.