The Impact of Diabetes Mellitus on Survival in Men with Clinically Localized Prostate Cancer Treated with Permanent Interstitial Brachytherapy

      Purpose: In general, patients with cancer of any kind with pre-existing diabetes are at increased risk for long-term, all-cause mortality compared to those without diabetes. It has been reported that diabetes mellitus is associated with a 20% lower risk of developing prostate cancer when compared to patients without diabetes. However, the influence of diabetes on biochemical progression free survival (bPFS), cause specific survival (CSS) and overall survival (OS) has not been documented following brachytherapy for clinically localized prostate cancer.
      Materials and Methods: From April 1995 to June 2006, 1,624 consecutive patients underwent permanent interstitial brachytherapy. A pre-brachytherapy diagnosis of diabetes was present in 199 patients (12.3%). The overall median followup was 7.8 years. Of the patients, 812 (50%) received supplemental external beam radiation therapy and 627 (38.0%) received androgen deprivation therapy. The median day 0 D90 was 118.7% of prescription dose. Cause of death was determined for each deceased patient. Patients with metastatic prostate cancer or castrate resistant disease without obvious metastases who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple clinical, treatment and dosimetric parameters were evaluated to determine the effect of diabetes on survival.
      Results: On average, patients with diabetes were statistically older (66.6 vs. 65.1 years, p = 0.010), more likely to be obese (BMI 29.8 vs. 27.3, p < 0.001), hypertensive (73.9% vs. 45.9%, p < 0.001) and have hypercholesterolemia (44.7% vs. 28.3%, p < 0.001) and/or coronary artery disease (23.1% vs. 15.9%, p = 0.009). In patients without and with diabetes mellitus, CSS was 97.2% vs. 100%, bPFS was 95.6% vs. 95.7% and overall survival was 74.3% vs. 54.9%. In a Cox regression analysis, overall survival in patients without diabetes was most closely related to patient age, coronary artery disease, tobacco consumption and duration of androgen deprivation therapy. In diabetic patients, overall survival was related to patient age and coronary artery disease with a strong trend for tobacco. bPFS was most closely related to percent positive biopsies and clinical stage in patients without diabetes and with percent positive biopsies and pre-treatment PSA in diabetic patients. In patients without diabetes, CSS was most closely associated with Gleason score and clinical stage. No patient with diabetes died of prostate cancer. Patients with diabetes mellitus were more likely to die of cardiovascular disease (10.6% vs. 6.9%) and were more likely to die of non-prostate cancers (7.5% vs. 5.1%).
      Conclusions: Diabetes mellitus does not impact cause-specific survival or biochemical progression-free survival following brachytherapy. However, overall survival is significantly less in diabetic patients as a result of increased risk of death from cardiovascular disease and non-prostate cancers.