#5996 Sex Differences in the Diagnosis of Advanced Cancer and Subsequent Outcome in People With CKD

Abstract

Background and Aims Incidence of cancer is increased in patients with chronic kidney disease (CKD), with a number of large population cohorts suggesting that lower estimated glomerular filtration rate (eGFR) increases overall risk of cancer death after adjustment for overlapping risk factors. In the general population, advanced cancer stage at presentation is associated with poorer outcomes. We sought to determine whether patients with CKD were more likely to present with advanced stage cancer, whether this impacted on their survival, and whether these factors varied by sex. Method Data were from Secure Anonymised Information Linkage Databank (SAIL), a Welsh primary care cohort with linkage to cancer and death registries. We included patients with a new cancer diagnosis between 2009 and 2020, and at least two kidney function tests before and within two years of diagnosis. eGFR based on serum creatinine (eGFRcr) was calculated using the CKD-EPI 2009 equation and measured in mL/min/1.73 m2. Albuminuria was not routinely available. Logistic regression models determined odds of presenting with advanced cancer (stage 3 or 4 at diagnosis). Cox proportional hazards models tested associations between eGFRcr and all-cause mortality (reference group: eGFR 75 to <90). Comparisons were made both between- and within-sex. Results There were 95,689 patients: 43,720 (45.7%) were female, mean age was 70.3 (SD 13.8) years in women and 71.4 (SD 11.4) years in men; median eGFRcr at baseline was 77 (IQR 63 – 89) mL/min/1.73 m2 in both women and men. Over a median follow-up time of 3.4 (IQR 0.9 – 5.7) years in women and 3.4 (IQR 0.9-5.5 years in men), there were 22,355 deaths in women and 27,681 in men. Adjusted for age, baseline eGFR, smoking status, number of comorbidities, deprivation and cancer site, men were slightly more likely to present with advanced cancer (aOR 1.02, 95% CI 1.01-1.04) and had higher hazards of death after cancer diagnosis than women (aHR 1.10 95% CI 1.08-1.13). In sex-stratified analyses, lower eGFRcr was weakly associated with higher odds of presenting with advanced cancer in men (eGFRcr 45-<60: OR 1.02, 95% CI 1.0-1.5; 30-<45: OR 1.02 95% CI 1.00-1.05; <30 OR 1.07 95% CI 1.03-1.11), but only in women with eGFRcr 45- <60 (OR 1.04 95% CI 1.02-1.06); Figure 1). Lower (and higher) eGFRcr was associated with higher hazards of death after cancer diagnosis in both men and women; however, the relative increase in hazards of death with eGFRcr <75 was stronger in women than in men, with a widening discrepancy as baseline eGFR decreased (Figure 1). Similar results were obtained for both men and women on a sensitivity analysis excluding participants diagnosis with myeloma and/or renal tract cancers. Conclusion Men were more likely than women to be diagnosed with advancer cancer and more likely to die after cancer diagnosis than women. Lower eGFR was associated with higher hazards of death after cancer diagnosis in both men and women. Despite an initial survival advantage compared to men, women with lower eGFR had disproportionately higher hazards of death. Though potential explanations are manifold, scrutiny of efficacy and safety of cancer treatments in people with CKD – particularly women with CKD – are warranted.