Real-world Assessment of Clinical Outcomes in Patients with Metastatic Renal Cell Carcinoma with or Without Sarcomatoid Features Treated with First-line Systemic Therapies.

BACKGROUND AND OBJECTIVE: Metastatic renal cell carcinoma (mRCC) patients have been reported to have better outcomes when treated with immunotherapies (IO) compared to targeted therapies (TT). This study aims to evaluate the impact of first-line systemic therapies on survival of mRCC patients with or without sarcomatoid features using real-world data. METHODS: Metastatic RCC patients of International mRCC Database Consortium (IMDC) intermediate or high risk, diagnosed from January 2011 to December 2022, treated with first-line systemic therapies, and with histological documentation of the presence or absence of sarcomatoid features in nephrectomy specimens were identified using the Canadian Kidney Cancer information system. Patients were classified by initial treatment: (1) targeted therapy (TT) used alone or (2) immunotherapy (IO)-based systemic therapies used in combination of either IO-IO or IO-TT. The inverse probability of treatment weighting using propensity scores was used to balance for covariates. Cox proportional hazard models were used to assess the impact of initial treatment received on overall survival (OS). KEY FINDINGS AND LIMITATIONS: Of the 1202 eligible patients, 791 were treated with TT and 411 with IO combinations. Of the patients, 76% were male, and the majority (91%) had a nephrectomy before systemic therapy. In nonsarcomatoid patients (639 TT and 320 IO patients), treatment with IO was associated with improved OS compared with patients treated with TT (median of 72 vs 48 mo, hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.50-0.80, objective response rate [ORR] of 38.5% for IO and 23.5% for TT). In sarcomatoid patients (152 TT and 91 IO patients), treatment with IO was associated with improved OS (median of 48 vs 18 mo, HR 0.41, 95% CI 0.26-0.64, ORR of 49.5% for IO and 13.8% for TT). Similar results were observed in patients with synchronous metastatic disease only. CONCLUSIONS AND CLINICAL IMPLICATIONS: IO treatment was associated with improved survival in mRCC patients. The magnitude of benefit is increased in patients with sarcomatoid mRCC, consequently, identifying the sarcomatoid status early on could help healthcare providers make a better treatment decision. PATIENT SUMMARY: Metastatic renal cell carcinoma (mRCC) patients of International mRCC Database Consortium intermediate and high risk, diagnosed from January 2011 to December 2022, treated with first-line systemic therapies, and with histological documentation of the presence or absence of sarcomatoid features in nephrectomy specimens were identified using the Canadian Kidney Cancer information system (CKCis). In this study, treatment with immunotherapy was associated to an improved survival and response rates for mRCC patients with and without sarcomatoid features. The magnitude of benefit is increased in patients with sarcomatoid mRCC.

Screening for Cognitive Dysfunction Using the Rowland Universal Dementia Assessment Scale in Adults With Sickle Cell Disease.

Importance: Adults with sickle cell disease (SCD) disproportionally experience early cognitive decline; however, guidance on the optimal screening strategy for cognitive dysfunction is lacking, and several available tools are biased by language, educational level, socioeconomic status, and race/ethnicity. The Rowland Universal Dementia Assessment Scale (RUDAS) was specifically designed for cognitive screening in multicultural populations. Objective: To ascertain the prevalence of suspected dementia in adults with SCD using the RUDAS, and to identify whether age, sex, educational level, several biological variables, and SCD complications were associated with RUDAS scores. Design, Setting, and Participants: This multicenter, bilingual, cross-sectional study was conducted in 2 SCD comprehensive care centers in Canada (Centre Hospitalier de l'Université Montréal in Montréal and University Health Network in Toronto). Participants were adults aged 18 years or older and were enrolled in the study between July 1, 2018, and July 30, 2019. All outpatients were eligible and offered study participation, unless they had an acute medical condition that required inpatient care or they were unable to follow study instructions. Interventions: The RUDAS was administered by trained personnel in either French or English, according to the patient's language preference. A questionnaire on social determinants of health was also administered, and participants underwent screening for anxiety and depression. Main Outcomes and Measures: Proportion of participants with RUDAS scores that were suggestive of dementia and the RUDAS score. Any score lower than 23 points was suggestive of dementia, a score between 23 and 27 points indicated a possible association with mild neurocognitive disorder, and a score higher than 27 points was normal. Results: A total of 252 adult patients with SCD were included (136 women [54.0%]; mean [range] age, 34.8 [18-75] years). Overall, 29 patients (11.5%) had RUDAS scores that were suggestive of dementia, and this proportion increased with age (15 [8.7%] in the 18-39 years age group, 10 [14.5%] in the 40-59 years age group, and 4 [36.4%] in the ≥60 years age group). The RUDAS scores were not associated with sex, language, SCD genotype, and SCD complications. The highest level of education was significantly associated with the RUDAS score; however, the association was small (η2 = 0.02; 95% CI, 0.00-0.07; P = .02). In a multivariable analysis, lower glomerular filtration rate (r = 0.40; 95% CI, 0.29-0.50; P < .001) and increasing age (r = -0.37; 95% CI, -0.47 to -0.26; P < .001), but not SCD genotype or disease severity, were associated with lower RUDAS scores. Conclusions and Relevance: This study found that using the RUDAS revealed a high prevalence of suspected dementia in adult patients with SCD that was associated with worsening kidney function and age. Cognition should be screened in all adult patients with SCD, regardless of age, disease severity, and SCD genotype; further validation of the RUDAS is ongoing.

Contemporary Assessment of Long-Term Survival Rates in Patients With Stage I Nonseminoma Germ-Cell Tumor of the Testis: Population-Based Comparison Between Surveillance and Active Treatment After Initial Orchiectomy.

BACKGROUND: Historical data demonstrated similar survival outcomes in patients with stage I nonseminoma germ-cell tumor of the testis (NSGCTT) subjected to either surveillance or active treatment (AT) after orchiectomy. However, data with long-term follow-up are unavailable. We tested contemporary treatment rates and their effect on cancer-specific mortality (CSM) and other-cause mortality (OCM) relative to surveillance, as well as after stratification between chemotherapy (CHT) versus retroperitoneal lymph node dissection (RPLND). PATIENTS AND METHODS: We identified patients with stage I NSGCTT with initial orchiectomy within the Surveillance, Epidemiology, and End Results (SEER) database (1988-2015). Subsequent surveillance versus CHT versus RPLND use rates were reported. Cumulative incidence plots and multivariable competing-risks regression (CRR) models were used after propensity score (PS) matching. These tests first compared surveillance versus AT (CHT vs. RPLND) and subsequently CHT versus RPLND. RESULTS: Of 5034 patients with stage I NSGCTT, 61.2%, 24.9%, and 13.9%, respectively, underwent surveillance, CHT, and RPLND. Between 1988 and 2015, surveillance (estimated annual percentage change [EAPC]: +1.1%, P < .001) and CHT (EAPC: +2.3%, P < .001) rates increased. RPLND rates decreased (EAPC: -5.7%; P < .001). After PS matching, CRR models failed to identify AT as an independent predictor of lower mortality relative to surveillance. However, after PS matching, CRR models identified RPLND as an independent predictor of lower CSM (hazard ratio, 0.26; P = .002) relative to CHT. No difference in OCM rates was recorded (hazard ratio, 1.25; P = .2). CONCLUSION: Surveillance and CHT use rates increased while RPLND decreased in the last two decades. Virtually the same outcomes were recorded between surveillance and AT. However, within AT, RPLND was associated with lower CSM than CHT.

Cost-utility of Sunitinib Versus Pazopanib in Metastatic Renal Cell Carcinoma in Canada using Real-world Evidence.

BACKGROUND AND OBJECTIVE: The development of new targeted therapies in kidney cancer has shaped disease management in the metastatic phase. Our study aims to conduct a cost-utility analysis of sunitinib versus pazopanib in first-line setting in Canada for metastatic renal cell carcinoma (mRCC) patients using real-world data. METHODS: A Markov model with Monte-Carlo microsimulations was developed to estimate the clinical and economic outcomes of patients treated in first-line with sunitinib versus pazopanib. Transition probabilities were estimated using observational data from a Canadian database where real-life clinical practice was captured. The costs of therapies, disease progression, and management of adverse events were included in the model in Canadian dollars ($Can). Utility and disutility values were included for each health state. Incremental cost-utility ratio (ICUR) and incremental cost-effectiveness ratios (ICER) were calculated for a time horizon of 5 years, from the Canadian Healthcare System perspective. RESULTS: The cost difference was $36,303 and the difference in quality-adjusted life year (QALY) was 0.54 in favour of sunitinib with an ICUR of $67,227/QALY for sunitinib versus pazopanib. The major cost component (56%) is related to best supportive care (BSC) where patients tend to stay for a longer period of time compared to other states. The difference in life years gained (LYG) between sunitinib and pazopanib was 1.21 LYG (33.51 vs 19.03 months) and the ICER was $30,002/LYG. Sensitivity analysis demonstrated the robustness of the model with a high probability of sunitinib being a cost-effective option when compared to pazopanib. CONCLUSION: When using real-world evidence, sunitinib is found to be a cost-effective treatment compared to pazopanib in mRCC patients in Canada.