Impact of Type 2 Diabetes Mellitus on Renal Cell Carcinoma Prognosis

Introduction: Metastatic renal cell carcinoma (mRCC) is incurable, with an estimated five-year survival of 12.3%. Type 2 diabetes mellitus (T2DM) has not been validated as a risk factor or poor prognostic factor in RCC, but its provascular pathophysiology has been associated with upregulation of growth factors that are also implicated in RCC. This study evaluated the impact of T2DM on time to metastatic disease in RCC, progression-free survival (PFS) and overall survival (OS). Patients and Methods: Patients at least 18 years of age were included in this single-health system retrospective cohort study if they had been treated at UNC Medical Center Healthcare System for mRCC between March 1, 2014 and March 1, 2019. Time from diagnosis to progression to metastatic disease, PFS, and OS were compared between patients with T2DM and patients without T2DM. PFS and OS was further compared between patients who initially presented with localized disease and those who presented with de novo metastatic disease in both the T2DM and non-T2DM arms. Results: A total of 147 mRCC patients were included in the study cohort (n=27 with T2DM and n=120 without T2DM). Among patients who initially presented with localized disease, a significantly shorter time to mRCC was observed in patients with T2DM (11.4 vs 33.2 months, HR 2.41, 95% CI 1.16-4.99; P=0.0006). However, significant differences in PFS (23.4 vs 14.6 months, HR 0.78, 95% CI 0.5-1.25; P=0.32), OS (58.6 vs 48.3 months, HR 0.86, 95% CI 0.48-1.54; P=0.63), and the prevalence of mRCC at time of initial diagnosis (P=0.29) were not observed. Conclusions: Patients with T2DM have a 2.4-fold higher risk of progressing to mRCC than non-T2DM patients. But, patients with T2DM were not more likely to be diagnosed with mRCC on initial presentation, and T2DM did not impact either PFS or OS. These data require future validation; however, the decreased time of progression to mRCC in the T2DM arm suggests that patients with T2DM may benefit from more diligent monitoring after a localized RCC diagnosis.Doctor of Pharmac