Comparison of Neoadjuvant and Adjuvant Chemotherapy in Muscle-invasive Bladder Cancer.

BACKGROUND: We use observational methods to compare impact of perioperative chemotherapy timing (ie, neoadjuvant and adjuvant) on overall survival (OS) in muscle-invasive bladder cancer because there is no head-to-head randomized trial, and patient factors may influence decision-making. PATIENTS AND METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients receiving cystectomy for muscle-invasive bladder cancer diagnosed between 2004 and 2013. Patients were classified as receiving neoadjuvant or adjuvant chemotherapy. Propensity of receiving neoadjuvant chemotherapy was determined using gradient boosted models. Inverse probability of treatment weighted survival curves were adjusted for 13 demographic, socioeconomic, temporal, and oncologic covariates. RESULTS: We identified 1342 patients who received neoadjuvant (n = 676) or adjuvant chemotherapy (n = 666) with a median follow-up of 23 months (interquartile range, 9-55 months). Inverse probability of treatment weighted adjustment allows comparison of the groups head-to-head as well as counterfactual scenarios (eg, effect if those getting one treatment were to receive the other). The average treatment effect (ie, "head-to-head" comparison) of adjuvant compared with neoadjuvant on OS was not significant (hazard ratio, 1.14; 95% confidence interval, 0.99-1.31). However, the average treatment effect of the treated (ie, the effect if the neoadjuvant patients were to receive adjuvant instead) was associated with a 33% increase in risk of mortality if they were given adjuvant therapy instead (hazard ratio, 1.33; 95% confidence interval, 1.12-1.57). CONCLUSION: Significant treatment selection bias was noted in peri-cystectomy timing, which limits the ability to discriminate differential efficacy of these 2 approaches with observational data. However, patients with higher propensity to receive neoadjuvant therapy were predicted to have increased OS with approach, in keeping with existing paradigms from trial data.

Multiparametric Magnetic Resonance Imaging Is Associated with Increased Medicare Spending in Prostate Cancer Active Surveillance.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) may improve prostate cancer risk stratification and decrease the need for repeat biopsies in men on prostate cancer active surveillance (AS). However, the impact of mpMRI on AS-related healthcare spending has not been established. OBJECTIVE: To characterize the impact of mpMRI on AS-related Medicare expenditures. DESIGN, SETTING, AND PARTICIPANTS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare files, we identified men ≥66 yr old with localized prostate cancer diagnosed during 2008-2013. OUTCOME MEASURES AND STATISTICAL ANALYSIS: With a validated algorithm, we classified men into AS with and without mpMRI groups. We then determined Medicare spending on AS in each group using inflation-adjusted, price-standardized Medicare payments for AS-related procedures (ie, prostate-specific antigen [PSA] tests, prostate biopsies, biopsy complications, and mpMRI). Multivariable median regression compared Medicare spending on AS for men who received mpMRI and those who did not. RESULTS AND LIMITATIONS: We identified 9081 men on AS with a median follow-up of 45 mo (interquartile range 29-64 mo). Thirteen percent (N = 1225) received mpMRI. On multivariable median regression, receipt of mpMRI was associated with an additional $447 (95% confidence interval $409-487) in Medicare spending per year. We observed greater frequency of AS-related procedures and higher spending for identical procedures (eg, PSA or prostate biopsy) in the mpMRI group than in the non-mpMRI group (all p < 0.001). CONCLUSIONS: Among Medicare beneficiaries on AS, mpMRI is associated with additional annual Medicare spending. Future studies are needed to determine optimal use of mpMRI during AS to maximize value. PATIENT SUMMARY: Prostate magnetic resonance imaging (MRI) helps physicians determine which prostate cancers are aggressive and which can be monitored safely. We studied whether using MRI during prostate cancer monitoring (also called active surveillance) resulted in increased healthcare spending. There was a modest increase in spending, but this may be worthwhile if the use of MRI allows physicians to monitor prostate cancer more accurately.

Evaluation of the Risks and Benefits of Computed Tomography Urography for Assessment of Gross Hematuria.

OBJECTIVE: To model the risk of radiation-induced malignancy from computed tomography urography (CTU) in evaluation of gross hematuria and contrast this with the benefits of urinary tract cancer detection when compared to renal ultrasound. METHODS: A PUBMED-based literature search was performed to identify model inputs. Estimates of radiation-induced malignancy rates were obtained from the Biological Effects of Ionizing Radiation VII report with dose extrapolation using the linear no-threshold model. RESULTS: Male gender and age over 50 years were associated with a relative risk of upper tract malignancy of 2.04 and 2.95, respectively. The risk of upper tract malignancy missed by renal ultrasound ranged from 0.055% in females under 50 to 0.51% in males over 50. Risk of CTU-induced malignancy with associated loss of life expectancy ranged from 0.25% and 0.027 years in females under 50 to 0.08% and 0.0054 years in males over 50. For CTU to be superior to renal ultrasound, an undiagnosed upper tract malignancy would have to carry a loss of life expectancy of 49.2 years in females under 50, 13.4 years in males under 50, 2.6 years in females over 50, and 1.1 years in males over 50. CONCLUSION: In low-risk patients, CTU for evaluation of gross hematuria may carry a significant risk of radiation-induced secondary malignancy relative to the diagnostic benefit offered over renal ultrasound.

Trends and appropriateness of perioperative chemotherapy for muscle-invasive bladder cancer.

INTRODUCTION: Contemporary guidelines recommend cystectomy with neoadjuvant or adjuvant cisplatin-based chemotherapy given with curative intent for patients with resectable muscle-invasive bladder cancer (MIBC). However, rates and appropriateness of perioperative chemotherapy utilization remain unclear. We therefore sought to characterize use of perioperative chemotherapy in older radical cystectomy MIBC patients and examine factors associated with use. METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified patients with MIBC diagnosed between 2004 and 2013 and treated with radical cystectomy. We classified patients into 3 treatment groups: cystectomy alone, neoadjuvant, or adjuvant chemotherapy. Chemotherapy was classified by regimen. We then fit a multinomial multivariable logistic regression model to assess association between patient factors with the receipt of each treatment. RESULTS: We identified 3,826 eligible patients. The majority (484; 65%) received cystectomy alone. Neoadjuvant (676; 18% overall, 69% cisplatin-based), and adjuvant chemotherapy (666, 17% overall, 55% cisplatin-based) were used in similar proportions of cystectomy patients. Over the study period, the odds of receiving adjuvant chemotherapy decreased by 7.5%, whereas neoadjuvant therapy increased by 27.5% (both P < 0.001). There was an increase in use of cisplatin-based regimens in the neoadjuvant setting (35 to 72%, P < 0.001), but not the adjuvant setting. Female gender, lower comorbidity, married status, and lower stage disease were associated with greater odds of receiving neoadjuvant chemotherapy (all P < 0.05). CONCLUSION: From 2004 to 2013 use of neoadjuvant chemotherapy for MIBC increased while use of adjuvant chemotherapy decreased. Future studies examining barriers to appropriate chemotherapy use, and the comparative effectiveness of neoadjuvant versus adjuvant chemotherapy are warranted.

Increasing Utilization of Multiparametric Magnetic Resonance Imaging in Prostate Cancer Active Surveillance.

OBJECTIVE: To characterize the use of multiparametric magnetic resonance imaging (mpMRI) in male Medicare beneficiaries electing active surveillance for prostate cancer. mpMRI has emerged as a tool that may improve risk-stratification and decrease repeated biopsies in men electing active surveillance. However, the extent to which mpMRI has been implemented in active surveillance has not been established. METHODS: Using Surveillance, Epidemiology, and End Results registry data linked to Medicare claims data, we identified men with localized prostate cancer diagnosed between 2008 and 2013 and managed with active surveillance. We classified men into 2 treatment groups: active surveillance without mpMRI and active surveillance with mpMRI. We then fit a multivariable logistic regression models to examine changing mpMRI utilization over time, and factors associated with the receipt of mpMRI. RESULTS: We identified 9467 men on active surveillance. Of these, 8178 (86%) did not receive mpMRI and 1289 (14%) received mpMRI. The likelihood of receiving mpMRI over the entire study period increased by 3.7% (P = .004). On multivariable logistic regression, patients who were younger, white, had lower comorbidity burden, lived in the northeast and west, had higher incomes and lived in more urban areas had greater odds of receiving mpMRI (all P < .05). CONCLUSION: From 2008 to 2013, use of mpMRI in active surveillance increased gradually but significantly. Receipt of mpMRI among men on surveillance for prostate cancer varied significantly across demographic, geographic, and socioeconomic strata. Going forward, studies should investigate causes for this variation and define ideal strategies for equitable, cost-effective dissemination of mpMRI technology.

Rate and Determinants of Completing Neoadjuvant Chemotherapy in Medicare Beneficiaries With Bladder Cancer: A SEER-Medicare Analysis.

OBJECTIVE: To determine the rate and determinants of neoadjuvant chemotherapy noncompletion in patients with muscle-invasive bladder cancer. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified all patients who underwent cystectomy between 2008-2013 and received chemotherapy within 6 months. Of these, 594 patients received neoadjuvant chemotherapy, defined as the presence of a claim for chemotherapy within the 180 days preceding cystectomy. Our primary outcome was noncompletion of neoadjuvant chemotherapy. We determined regimen-specific cut points for noncompletion based on clinical trials and national guidelines. RESULTS: Over the study period, 174 of 594 patients (29%) did not complete neoadjuvant chemotherapy. Noncompleters and completers received a median interquartile range of 4.4 (3.0-8.0) and 10.0 (7.7-11.2) weeks of chemotherapy, respectively. A total of 391 (66%) patients received a cisplatin-based regimen and 203 (34%) patients received an alternative regimen, with 27% and 33% not completing chemotherapy, respectively. After adjusting for covariates, age and geographic region were independently associated with failing to complete chemotherapy. CONCLUSION: Nearly 30% of patients who received neoadjuvant chemotherapy did not complete their regimen. Advanced age and nonclinical factors, such as practice patterns in certain geographic regions, may influence a patient's likelihood of successfully completing chemotherapy.