Sex differences in the diagnosis of advanced cancer and subsequent outcome in people with chronic kidney disease: an analysis of a national population cohort

Abstract Background In the general population, advanced cancer stage at presentation is associated with poorer health outcomes. People with chronic kidney disease (CKD) have increased incidence and mortality from most cancer types. We sought to determine whether people with CKD were more likely to present with advanced stage cancer, whether this was associated with survival, and whether these associations varied by sex. Methods Data were from Secure Anonymised Information Linkage Databank (SAIL), a Welsh primary care database with linkage to cancer and death registries. We included patients with a de- novo cancer diagnosis (2011-2017), and at least two kidney function tests in the two years prior to diagnosis. Estimated glomerular filtration rate based on serum creatinine (eGFRcr) was calculated using the CKD-EPI 2009 equation (mL/min/1.73m 2 ). Logistic regression models determined odds of presenting with advanced cancer (stage 3 or 4 at diagnosis) by different values of eGFRcr at baseline. Cox proportional hazards models tested associations between eGFRcr at baseline and all-cause mortality risk (reference eGFR 75 to <90). Findings There were 66,128 patients: 30,857 (46.7%) were female, mean age was 69.1 (standard deviation [SD] 13.8) years in females and 70.6 (SD 11.1) years in males; median eGFRcr at baseline was 78 (interquartile range [IQR] 63 – 90) mL/min/1.73m 2 in both females and males. Over a median follow-up time of 3.1 (IQR 0.5 – 5.7) years in females and 2.9 (IQR 0.5-5.5) years in males, there were 17,303 deaths in females and 20,855 in males. An eGFRcr <30 was associated with higher odds of presenting with advanced cancer in males (OR 1.33 95% CI 1.09-1.62), but not in females (OR 1.17 95% CI 0.92-1.50); positive associations were primarily driven by prostate and breast cancers. With lower eGFRcr, hazards of cancer death increased in both sexes, but lower eGFRcr was associated with greater hazards of cancer death in females (eGFRcr <30: HR 1.71, 95% CI 1.56-1.88, p<0.001; male versus female comparison HR 0.88, 95% CI 0.78-0.90; p=0.037). Interpretation CKD was not associated with substantially higher odds of presenting with advanced cancer across most cancer sites (except prostate and breast), but was associated with reduced survival. Despite an initial survival advantage compared to males, females with CKD had disproportionately higher hazards of death. Though potential explanations for reduced survival after a cancer diagnosis are manifold, scrutiny of access to, efficacy, and safety of cancer treatments in people with CKD – particularly females with CKD – are warranted. Funding Chief Scientist Office (Scotland) Postdoctoral Lectureship (PCL/20/10) and University of Sydney/University of Glasgow Office of Global Engagement Collaboration Partnership (9241562498).