Impact of overweight and obesity on US renal cell carcinoma incidence trends (1995-2018)

In the United States, renal cell carcinoma (RCC) incidence and the prevalence of obesity, an established risk factor for RCC, have been increasing for several decades. RCC is more common among older individuals. We sought to quantify the contribution of excess adiposity to the rising incidence of RCC among individuals 60 years or older. National Institutes of Health-American Association of Retired Persons Diet and Health Study data (n = 453 859 participants, enrolled in 1995-1996, age at enrollment 50-71 years) were used to estimate multivariable-adjusted hazard ratios (HRs) for RCC across body mass index categories and HRs associated with smoking. Population attributable fractions (PAFs) were calculated using estimated HRs and annual overweight/obesity prevalence from the National Health Interview Survey (1985-2008). PAF estimates were combined with RCC incidence from Surveillance, Epidemiology and End Results-13 to calculate annual percent changes in RCC incidence attributable (and unrelated) to overweight/obesity. We found that between 1995 and 2018, among individuals aged 60 years and older, PAF for overweight/obesity increased from 18% to 29% for all RCCs. In comparison, the PAF for smoking declined from 12% to 9%. RCC incidence increased 1.8% per year (95% confidence interval [CI] 1.5%-2.1%) overall, while RCC incidence attributable to overweight/obesity increased 3.8% per year (95%CI 3.5%-4.2%) and RCC incidence unrelated to overweight/obesity increased 1.2% per year (95% CI 0.9%-1.4%). In conclusion, overweight/obesity appears to have contributed importantly to the rising incidence of RCC in the United States since the mid-1990s. Public health interventions focused on reducing overweight and obesity could help substantially in curbing this trend.     

Risk Factors for Renal Cell Carcinoma in a Japanese Population

The incidence of renal cell carcinoma (RCC) is high in Western and Northern Europe and North America, andlow in Asia. Although the incidence of RCC in Japan is lower than the rates in the other industrialized countries,there is no doubt that it is increasing. In this paper, we would like to introduce the summary of findings of JACCstudy, which evaluate the risk factors for RCC in a Japanese population. JACC study suggests nine risk factors(i.e., smoking, obesity, low physical activity, hypertension, diabetes mellitus, kidney diseases, beef, fondness forfatty food and black tea) and one preventive factor (i.e., starchy roots such as taro, sweet potato and potato) ina Japanese population. In Japan, however, drinking black tea may be a surrogate for westernized dietary habitswhile eating starchy roots may be a surrogate for traditional Japanese dietary habits. Further studies may beneeded to evaluate risk factors for RCC because the number of cases is small in our studies.     

History of treated hypertension and diabetes mellitus and risk of renal cell cancer.

BACKGROUND: An increased risk of renal cell cancer (RCC) has been reported in subjects with hypertension. Whether this association may vary according to sex, smoking, obesity, or RCC clinical presentation is unclear. Results on the link between diabetes mellitus and RCC are inconclusive. PATIENTS AND METHODS: We conducted an Italian multicenter case-control study, including 767 (494 men, 273 women) incident cases of RCC, under 80 years of age, and 1534 hospital controls, frequency-matched to cases. Multiple logistic regression models, conditioned to center, sex, and age, and adjusted for period of interview, education, smoking, and body mass were used to estimate odds ratios (OR). RESULTS: Compared with subjects never treated, patients with a history of treated hypertension [OR = 1.7, 95% confidence interval (CI) 1.4-2.1] reported an excess risk of RCC. This pattern was confirmed in different strata of sex, education, smoking habits, body mass, tumor histological type, stage, or grade. The attributable risk of RCC for treated hypertension in this population was 16%. A slight, nonsignificant increased risk was found for history of diabetes mellitus (OR = 1.3, 95% CI 0.9-1.7). CONCLUSION: A possible causal role of hypertension in renal cell carcinogenesis is supported by the consistency of the direct association.     

Cancer surveillance using registry data: Results and recommendations for the Lithuanian national prostate cancer early detection programme

IntroductionWe describe long term trends in prostate cancer epidemiology in Lithuania, where a national prostate specific antigen (PSA) test based early detection programme has been running since 2006.MethodsWe used population-based cancer registry data, supplemented by information on PSA testing, life expectancy and mortality from Lithuania to examine age-specific prostate cancer incidence, mortality and survival trends among men aged 40+ between 1978 and 2009, as well as life expectancy of screening-eligible men, and the proportion of men with a first PSA test per year since the programme started.ResultsThe number of prostate cancer patients rose from 2.237 in 1990–1994 to 15.294 in 2005–2009. By 2010, around 70% of the eligible population was tested, on average around two times. The early detection programme brought about the highest prostate cancer incidence peaks ever seen in a country to date. Recent incidence and survival rises in the age groups 75–84 suggest PSA testing in the elderly non-eligible population. Life expectancy of men aged 70–74 indicates that less than 30% of patients will live for 15 years and may have a chance to benefit from early detection.ConclusionsEarly detection among men aged 70–74, and particularly among the elderly (75+) may have to be reconsidered. Life expectancy assessment before testing, avoiding a second test among men with low PSA values and increasing the threshold for further evaluation and the screening interval may help reducing harm. Publishing information on treatment modalities, side-effects and patient reported quality of life is recommended.     

Alcohol consumption,tobacco smoking,and subsequent risk of renal cell carcinoma: The JPHC study

The effects of alcohol consumption and tobacco smoking on renal cell carcinoma (RCC) incidence have not been well-investigated in Asian populations. Here, we evaluated these effects in a large Japanese prospective cohort. We collected data on eligible participants in the Japan Public Health Center-based Prospective Study, and undertook multivariable-adjusted Cox proportional hazards regression to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of RCC incidence. We identified 340 cases (230 men and 110 women) among the 105 663 eligible participants (50 262 men and 55 741 women), who were followed for an average of 19.1 years, with a cumulative total of 2 020 364 person-years. A slightly inverse but nonsignificant association was observed between alcohol drinking and RCC incidence. In contrast, the risk of RCC was increased in those with heavy smoking (≥40 pack-years) when men and women were combined (HR 1.50; 95% CI, 1.01-2.25). We identified no significant association between alcohol consumption and RCC incidence. In contrast, heavy smoking (≥40 pack-years) was associated with a significant increase in incidence.     

Lifestyle factors, exposures, genetic susceptibility, and renal cell cancer risk: a review

Malignant kidney tumors account for approximately 2% of all new primary cancer cases diagnosed in the United States, with an estimated 30,000 cases occurring annually. Although a variety of agents, chemical and biological, have been implicated as causal agents in the development of renal cell carcinoma (RCC), the etiology remains enigmatic. The strongest association has been developed between cigarette smoking and renal cancer however consistent, positive associations between RCC and obesity, diabetes, and hypertension have also been reported. In addition, more recent investigations of familial kidney cancer syndromes indicate that a strong genetic component contributes to RCC development. Several genes have been identified through investigation of familial kidney cancer syndromes. This review article describes recent trends in RCC incidence and the currently identifiable etiological causes that account for approximately half of the RCC cases diagnoses. The remainder of this review then focuses on additional risk factors that have thus far not been well examined but may be helpful in explaining the increasing incidence trends and the geographic or racial variation observed nationally and worldwide.     

A Dose-finding Study Followed by a Phase II Randomized,Placebo-controlled Trial of Chemoradiotherapy With or Without Veliparib in Stage III Non–small-cell Lung Cancer: SWOG 1206 (8811)

BackgroundWe conducted a 2-part study to evaluate the incorporation of veliparib, a PARP inhibitor, into chemoradiotherapy (CRT) for stage III non–small-cell lung cancer.Patients and MethodsIn the phase I part, patients were treated successively at 3 dose levels of veliparib (40, 80, and 120 mg) twice daily during CRT. In the phase II part, patients were randomized to receive veliparib or placebo during thoracic radiotherapy with concurrent weekly carboplatin and paclitaxel, followed by 2 cycles of consolidation carboplatin and paclitaxel with veliparib or placebo. The study was prematurely discontinued owing to the emergence of adjuvant immunotherapy as standard of care.ResultsOf 21 patients enrolled in phase I, 2 patients developed dose-limiting toxicities (DLTs): 1 grade 3 esophagitis with dysphagia (at 40 mg) and 1 grade 3 esophagitis with dehydration (at 80 mg). No DLTs were seen at veliparib dose of 120 mg twice daily, which was selected for the phase II part that enrolled 31 eligible patients. Progression-free survival (PFS) was not different between the 2 arms (P = .20). For the veliparib and placebo arms, response rates were 56% and 69%, PFS at 1 year 47% and 46%, and overall survival at 1 year 89% and 54%, respectively.ConclusionVeliparib with CRT was feasible and well tolerated. Efficacy could not accurately be determined because of early study closure. Nonetheless, there is enthusiasm for the evaluation of PARP inhibitors in lung cancer as predictive biomarkers are being developed and combinations with immunotherapy are attractive.     

Trends in Renal-Cell Carcinoma Incidence and Mortality in the United States in the Last 2 Decades: A SEER-Based Study

Background

Renal-cell carcinoma (RCC) is one of the common malignancies in the United States. RCC incidence and mortality have been changing for many reasons. We performed a thorough investigation of incidence and mortality trends of RCC in the United States using the cell Surveillance, Epidemiology, and End Results (SEER) database.

Breast cancer incidence and mortality in women in China: temporal trends and projections to 2030

Objective:Breast cancer was the most common cancer and the fifth cause of cancer deaths among women in China in 2015. The evaluation of the long-term incidence and mortality trends and the prediction of the future burden of breast cancer could provide valuable information for developing prevention and control strategies.Methods:The burden of breast cancer in China in 2015 was estimated by using qualified data from 368 cancer registries from the National Central Cancer Registry. Incident cases and deaths in 22 cancer registries were used to assess the time trends from 2000 to 2015. A Bayesian age-period-cohort model was used to project the burden of breast cancer to 2030.Results:Approximately 303,600 new cases of breast cancer (205,100 from urban areas and 98,500 from rural areas) and 70,400 breast cancer deaths (45,100 from urban areas and 24,500 from rural areas) occurred in China in 2015. Urban regions of China had the highest incidence and mortality rates. The most common histological subtype of breast cancer was invasive ductal carcinoma, followed by invasive lobular carcinoma. The age-standardized incidence and mortality rates increased by 3.3% and 1.0% per year during 2000–2015, and were projected to increase by more than 11% until 2030. Changes in risk and demographic factors between 2015 and 2030 in cases are predicted to increase by approximately 13.3% and 22.9%, whereas deaths are predicted to increase by 13.1% and 40.9%, respectively.Conclusions:The incidence and mortality of breast cancer continue to increase in China. There are no signs that this trend will stop by 2030, particularly in rural areas. Effective breast cancer prevention strategies are therefore urgently needed in China.     

An investigation of risk factors for renal cell carcinoma by histologic subtype in two case‐control studies

To investigate whether renal cell carcinoma (RCC) histologic subtypes possess different etiologies, we conducted analyses of established RCC risk factors by subtype (clear cell, papillary and chromophobe) in two case‐control studies conducted in the United States (1,217 cases, 1,235 controls) and Europe (1,097 cases, 1,476 controls). Histology was ascertained for 706 U.S. cases (58% of total) and 917 European cases (84%) through a central slide review conducted by a single pathologist. For the remaining cases, histology was abstracted from the original diagnostic pathology report. Case‐only analyses were performed to compute odds ratios (ORs) and 95% confidence intervals (CI) summarizing subtype differences by age, sex and race. Case‐control analyses were performed to compute subtype‐specific ORs for other risk factors using polytomous regression. In case‐only analyses, papillary cases (N = 237) were older (OR = 1.2, 95% CI = 1.1–1.4 per 10‐year increase), less likely to be female (OR = 0.5, 95% CI = 0.4–0.8) and more likely to be black (OR = 2.6, 95% CI = 1.8–3.9) as compared to clear cell cases (N = 1,524). In case‐control analyses, BMI was associated with clear cell (OR = 1.2, 95% CI = 1.1–1.3 per 5 kg/m² increase) and chromophobe RCC (N = 80; OR = 1.2, 95% CI = 1.1–1.4), but not papillary RCC (OR = 1.1, 95% CI = 1.0–1.2; test versus clear cell, p = 0.006). No subtype differences were observed for associations with smoking, hypertension or family history of kidney cancer. Our findings support the existence of distinct age, sex and racial distributions for RCC subtypes, and suggest that the obesity‐RCC association differs by histology.     

A Phase I,Open-Label Study of Trebananib Combined With Sorafenib or Sunitinib in Patients With Advanced Renal Cell Carcinoma

BackgroundTrebananib, an investigational peptibody, binds to angiopoietin 1 and 2, thereby blocking their interaction with Tie2.Patients and MethodsThis open-label phase I study examined trebananib 3 mg/kg or 10 mg/kg intravenous (I.V.) once weekly plus sorafenib 400 mg twice per day or sunitinib 50 mg once per day in advanced RCC. Primary end points were adverse event incidence and pharmacokinetics.ResultsThirty-seven patients were enrolled. During trebananib plus sorafenib administration (n = 17), the most common treatment-related adverse events (TRAEs) included rash (n = 12; 71%), diarrhea (n = 12; 71%), hypertension (n = 11; 65%), and fatigue (n = 11; 65%); grade ≥ 3 TRAEs (n = 7; 41%); and 2 patients (12%) had peripheral edema. During trebananib plus sunitinib administration (n = 19), the most common TRAEs included diarrhea (n = 14; 74%), fatigue (n = 13; 68%), hypertension (n = 11; 58%), and decreased appetite (n = 11; 58%); grade ≥ 3 TRAEs (n = 13; 68%); and 8 (42%) patients had peripheral edema. Trebananib did not appear to alter the pharmacokinetics of sorafenib or sunitinib. No patient developed anti-trebananib antibodies. Objective response rates were 29% (trebananib plus sorafenib) and 53% (trebananib plus sunitinib).ConclusionThe toxicities of trebananib 3 mg/kg or 10 mg/kg I.V. plus sorafenib or sunitinib in RCC were similar to those of sorafenib or sunitinib monotherapy, with peripheral edema being likely specific to the combinations. Antitumor activity was observed.     

Cancer in the oldest old in the United States: Current statistics and projections

ObjectivesThe oldest old population in the US, defined as aged ≥ 85 years, is projected to double from 4.3 million in 2000 to 9.6 million in 2030. The purpose of this study was to assess the current and projected cancer burden in the oldest old.Materials and MethodsThis was a retrospective cohort study using the national Surveillance, Epidemiology, and End Results (SEER) tumor registry. Historical trends were assessed and projections were created for the top 10 cancers by incidence, and also by proportion of cancer deaths for those aged ≥ 85 years.ResultsCurrently, the oldest old experiences about 7% of annual new cancer cases and 14% of cancer deaths. The most common cancers by incidence per 100,000 people are colorectal (336), lung (297), breast (254), and prostate (165), while the leading causes of cancer deaths are lung (19%), colorectal (13%), prostate (9%), and breast (7%). The incidences of non-Hodgkin lymphoma, melanoma, bladder, lung, and pancreatic cancers have been increasing, while those of other cancers are stable or decreasing. A substantial proportion of the oldest old (24%) had prior primary cancers. If historical trends continue to 2030, we project that 9% of newly diagnosed cancer cases and 23% of cancer deaths annually will occur in the oldest old.ConclusionThe oldest old may have unique cancer incidence and mortality. To manage a projected major increase in the burden of cancer care, substantial investments in geriatric oncology research, education, and practice are needed.     

Screening Mammography Findings in Women With Chronic Kidney Disease on a Renal Transplant Waiting List

BackgroundThe incidence of breast cancer has been reported to be increased in people with chronic kidney disease (CKD). Thus, breast cancer screening is stated to be mandatory. However, it is as yet unclear what age group or what type of breast structure indicate a need for mammography. This study aimed to evaluate the effects of age and breast parenchymal density on mammography findings. The rate of detection of calcification from mammographies increased in dialysis patients with CKD. The associations of calcifications with comorbid pathologies were also evaluated.Patients and MethodsPatients were divided into the two age groups of 40 to 49.9 years and ≥ 50 years. The patients were asked about smoking habits, hypertension, diabetes mellitus, the pathology that caused CKD, state of hemodialysis, and, if relevant, the type and duration of dialysis.ResultsThe mean age of the 55 patients included in this study was 54.8 years, and 78.2% (n = 43) were ≥ 50 years old. The rate of malignancy across the entire group was 3.6%. No association was found between breast arterial calcification and cigarette smoking, hypertension, diabetes mellitus, state of dialysis, duration of dialysis, and breast parenchymal density in any age group.ConclusionA pretransplantation evaluation of CKD patients may include a breast screening program for patients aged 40 to 49.9 and for the patients aged ≥ 50. Breast parenchymal density was demonstrated to have no effect on the findings, and no association was found between calcifications and comorbid pathologies.     

Socioeconomic factors associated with risk of upper aerodigestive tract cancer in Europe

IntroductionIn the European Union, there are 180,000 new cases of upper aerodigestive tract (UADT) cancer cases per year – more than half of whom will die of the disease. Socioeconomic inequalities in UADT cancer incidence are recognised across Europe. We aimed to assess the components of socioeconomic risk both independently and through their influence on the known behavioural risk factors of smoking, alcohol consumption and diet.Patients and methodsA multicentre case–control study with 2198 cases of UADT cancer and 2141 controls from hospital and population sources was undertaken involving 14 centres from 10 countries. Personal interviews collected information on demographics, lifetime occupation history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression.ResultsWhen controlling for age, sex and centre significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR = 1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators – comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR = 1.60 (1.28, 2.00); and for unemployment OR = 1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR = 1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community).ConclusionSocioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet.     

Elevated Cardiovascular Disease Risk in Patients With Chronic Myelogenous Leukemia Seen in Community-based Oncology Practices in the United States

IntroductionCurrent National Comprehensive Cancer Network guidelines recommend that comorbidities, including cardiovascular disease (CVD), be considered when selecting tyrosine kinase inhibitors for the treatment of chronic myelogenous leukemia (CML). We report here the prevalence of CVD and its risk factors in patients with CML treated by community-based United States (US) oncologists.Patients and MethodsAdult patients with a confirmed diagnosis of CML and ≥ 1 encounter after the first date of CML diagnosis in an electronic medical record database between January 1, 2005 and October 31, 2014 were enrolled. CVD conditions/risk factors were assessed at baseline and during the 5-year follow-up period using International Classification of Diseases, 9th Revision, Clinical Modification diagnoses codes and information from physician progress notes. One-year prevalence estimates were age- and gender-standardized for comparison to annual rates in the US population.ResultsA total of 1639 patients were included. At 5-year follow-up, the prevalence of CVD conditions and CVD risk factors was 33.0% and 77.7%, respectively. Compared with the general US adult population, the standardized prevalence rates at 1 year in patients with CML were significantly higher by factors of 1.3 to 3.5 times for CVD conditions, and 20% to 40% significantly higher for hypertension, diabetes, and obesity (P < .001). The prevalence of cardiovascular risk factors was not significantly higher in patients residing in the US Stroke Belt.ConclusionThe increased risk of CVD observed in this real-world analysis of patients with CML underscores the importance of current National Comprehensive Cancer Network recommendations to consider cardiovascular risk when selecting tyrosine kinase inhibitors.     

Cancer incidence in the United Kingdom: projections to the year 2030

Background:

Projections of cancer incidence are important for planning health services and to provide a baseline for assessing the impact of public health interventions.

Methods:

Rates estimated from smooth function age–period–cohort modelling of cancer incidence data from Great Britain 1975 to 2007 are extrapolated to 2030 and applied to UK population projections. Prostate and breast cancer projections take into account the effect of screening.

Results:

Overall rates of cancer are projected to be stable over the next 20 years, but this masks individual changes. In both sexes, age-standardised rates of cancers of the stomach, larynx, bladder and leukaemia are projected to fall by ⩾1% per year, whereas cancers of the lip, mouth and pharynx (ICD-10 C00-C14) and melanoma are projected to increase by ⩾1% per year. The growing and aging populations will have a substantial impact: numbers of cancers in men and women are projected to increase by 55% (from 149 169 to 231 026) and 35% (from 148 716 to 200 929), respectively, between 2007 and 2030. The model used yields similar results to those of Nordpred, but is more flexible.

Conclusion:

Without new initiatives for smoking and obesity reduction, the number of cancers in the United Kingdom will increase substantially reflecting the growing and aging populations.     

Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings

BackgroundThe European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study provided sorafenib to advanced renal cell carcinoma (RCC) patients in whom previous systemic therapy had failed. The study assessed the safety and use of sorafenib for the treatment of advanced RCC in a large community-based patient population across 11 countries in Europe.Patients and methodsEU-ARCCS was a single-arm, open-label trial of sorafenib in advanced RCC patients. End points included safety, time to progression, progression-free survival (PFS), and disease control rate (DCR). Subgroup analyses included age, Eastern Cooperative Oncology Group performance status, histology, prior therapy, and number and sites of metastases.ResultsAbout 1159 advanced RCC patients were enrolled. Most patients (94%) experienced drug-related adverse events (AEs) of any grade, with the most common grade ≥3 AEs including hand–foot skin reaction (13%), diarrhea (7%), fatigue (7%), hypertension (6%), and rash/desquamation (5%). The incidence of AEs in the subgroups was similar to that in the overall population. Median PFS was 6.6 months; DCR at ≥8 and ≥12 weeks was 85% and 78%, respectively.ConclusionsThe sorafenib safety profile in European community-based practice settings was similar to that reported in clinical trials. The heterogeneous advanced RCC patient population in EU-ARCCS permitted assessment of sorafenib in important subpopulations of advanced RCC patients.     

Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review

Renal cell carcinoma (RCC), the most common form of kidney cancer, initially has an asymptomatic clinical course; 25-30% of patients present with metastatic disease at time of diagnosis. Worldwide incidence and mortality rates are rising at a rate of approximately 2-3% per decade. Metastatic RCC (mRCC) is one of the most treatment-resistant malignancies; outcomes are generally poor and median survival after diagnosis is less than one year. Surgery and chemotherapy have limited or no effect, leaving mRCC patients underserved in the realm of cancer treatment. As the world's population ages and the prevalence of risk factors (obesity, hypertension) increases, the burden of mRCC is predicted to increase significantly. With a shift in treatment of mRCC to novel therapies, such as molecularly targeted therapies (MTTs) (e.g., sorafenib and sunitinib), clinicians, payers, and other healthcare decision-makers must re-evaluate the optimal role for new treatments. Timely understanding of the burden of mRCC on individuals and society clearly is needed at this juncture. Using a comprehensive literature review, we assessed the epidemiologic, economic, and health-related quality of life (HRQOL) burdens of mRCC. The annual incidence of mRCC in major European countries, the US, and Japan ranges from 1500 to 8600 cases. However, prevalence data were lacking. The estimated economic burden of mRCC is large; $107-$556 million (2006 USD) in the US and $446 million-$1.6 billion (2006 USD) collectively in select countries worldwide. MTTs have potential to reduce the burden of mRCC and provide substantial value beyond their clinical effectiveness.     

Cabozantinib Safety With Different Anticoagulants in Patients With Renal Cell Carcinoma

BackgroundIn patients with renal cell carcinoma (RCC) on cabozantinib, venous thromboembolism (VTE) management remains challenging due to limited safety data regarding direct oral anticoagulants (DOACs) use in conjunction with cabozantinib. We investigated the safety of cabozantinib with different anticoagulants in patients with RCC.MethodsIn this retrospective multicenter study (9 sites), patients with advanced RCC were allocated into 4 groups: (1) cabozantinib without anticoagulation, cabozantinib with concomitant use of (2) DOACs, (3) low molecular weight heparin (LMWH), or (4) warfarin. The primary safety endpoint was the proportion of major bleeding events (defined per International Society on Thrombosis and Hemostasis criteria). The primary efficacy endpoint was the proportion of new/recurrent VTE while anticoagulated.ResultsBetween 2016 and 2020, 298 patients with RCC received cabozantinib (no anticoagulant = 178, LMWH = 41, DOAC = 64, and warfarin = 15). Most patients had clear cell histology (78.5%) and IMDC intermediate/poor disease (78.2%). Cabozantinib was first, second, or ≥ third line in 21.8%, 31.9%, 43.3% of patients, respectively. Overall, there was no difference in major bleeding events between the no anticoagulant, LMWH, and DOAC groups (P = .088). Rate of new/recurrent VTE was similar among anticoagulant groups. Patients with a VTE had a statistically significantly worse survival than without a VTE (HR 1.48 [CI 95% 1.05-2.08, P = .02]).ConclusionThis real-world cohort provides first data on bleeding and thrombosis complications in patients with RCC treated with cabozantinib with or without concurrent anticoagulation. DOACs appear safe for VTE treatment for patients with RCC on cabozantinib, but optimized anticoagulation management, including individualized risk-benefit discussion, remains important in clinical practice.     

The Effect of Targeted Therapy on Overall Survival in Advanced Renal Cancer: A Study of the National Surveillance Epidemiology and End Results Registry Database

IntroductionWith the advent and availability of targeted therapy, the treatment of advanced/metastatic renal cell carcinoma (RCC) underwent a drastic change in 2005. The effect of this change on clinical outcome within the population has not been studied. The aim of this study was to evaluate the overall survival (OS), before, and after availability of targeted therapy, for advanced RCC cases in the population-based Surveillance, Epidemiology, and End Results (SEER) cancer registry.Materials and MethodsAll advanced (regional and distant stage) RCC cases diagnosed within the 2000 to 2008 time periods were included. Because SEER does not report the exact therapy, and because targeted therapy was initially approved in 2005, we evaluated and compared the OS outcomes of advanced RCC cases diagnosed between the years 2000 and 2003 (before targeted therapy era) with that of those diagnosed between 2005 and 2008 (targeted therapy era).ResultsThere was a significant improvement in OS for advanced RCC patients treated in the targeted therapy era (n = 12,330) compared with those treated in the era before targeted therapy (n =11,565) (median OS 20 months vs. 15 months, P = .0006). Multivariate analysis revealed that in the time period before targeted therapy, age older than 65 years, black race, and lack of nephrectomy were predictors of a shorter OS.ConclusionIn univariate and multivariate analysis, targeted therapy demonstrated improvement in OS. Increasing access to targeted therapies is likely to improve outcomes in advanced RCC.