Association of diabetes mellitus and metformin use with biochemical recurrence in patients treated with radical prostatectomy for prostate cancer

Purpose: The impact of diabetes mellitus (DM) and metformin use on biochemical recurrence (BCR) in patients treated with radical prostatectomy (RP) remains controversial. Methods: We retrospectively evaluated 6,863 patients who underwent RP for clinically localized PC between 2000 and 2011. Univariable and multivariable Cox regression models addressed the association of DM and metformin use with BCR. Results: Overall, 664 patients had a diagnosis of DM from which 287 (43 %) were on metformin and 377 (57 %) were on anti-diabetics other than metformin. DM and metformin were not associated with any clinicopathologic features (p values >0.05). Within a median follow-up of 25 months (interquartile range 35 months), 774 (11.3 %) patients experienced BCR. Actuarial 5-year biochemical-free survival was 83 % for non-diabetic, 79 % for diabetic patients without metformin use, and 85 % for diabetic patients with metformin use (log rank p = 0.17). In uni- and multivariable Cox regression analyses with the non-diabetic group as referent, DM without metformin use (HR = 0.99; 95 % CI 0.75-1.30, p = 0.65) and DM with metformin use (HR = 0.84, 95 % CI 0.58-1.22, p = 0.36) were not associated with BCR after RP. A subgroup analysis stratified by nodal status, surgical margins, tumor stage, and Gleason sum did not reveal any significant association between DM, use of metformin and risk of BCR. Conclusions: We found no association between DM or metformin use and cancer-specific features or BCR in patients treated with RP. The effect of DM and metformin on complications, wound healing and overall survival needs to be assessed in similar cohorts.