Effect of metformin on prostate cancer outcomes after radical prostatectomy

Abstract

Objective Recent studies have shown a relative risk reduction in the incidence of prostate cancer in patients taking metformin. However there are conflicting findings on the impact of metformin on established cases of prostate cancer. In this study we evaluated the impact of metformin on survival and pathological outcomes in established prostate cancer. Materials and Methods We retrospectively identified 12,052 patients who underwent radical prostatectomy (RP) between 1997 and 2010 at Mayo Clinic. Among these 885 (7.3%) were diabetics, including 323 taking and 562 not taking metformin. Kaplan-Meier method was utilized to calculate rates of biochemical recurrence (BCR), systemic progression (SP), and all-cause mortality (ACM). Cox models were used to estimate the metformin hazard ratio (HR) adjusted for clinical and pathologic variables. Results and Conclusions Median follow-up was 5.1 years. In univariate analysis, metformin HR [95% CI] was not significant for BCR (1.13 [0.84, 1.52], p=0.40), SP (1.37 [0.69, 2.72], p=0.37), and ACM (1.32 [0.84, 2.05], p=0.23). After adjusting for covariates of interest, the HRs for metformin among diabetics remained non-significant for BCR (0.91 [0.67, 1.24], p=0.56), SP (0.83 [0.39, 1.74], p=0.62), and ACM (1.16 [0.73, 1.86], p=0.53). No difference was seen between metformin users and non-users in the final pathologic Gleason score (p=0.33), stage (p=0.1), rate of positive surgical margins (p=0.29), or tumor volume (p=0.76). Metformin use was not associated with a risk reduction in BCR, SP, or ACM. Besides presenting survival data, our results describing metformin's effect on final pathology are unique.

Antidiabetic drugs influence molecular mechanisms in prostate cancer

“…For example, in 2013, Spratt et al published the first clinical retrospective data indicating that metformin use may improve progression free survival and PCa mortality. 26 In the present study we demonstrate no significant differences concerning pathological stage and Gleason score of different diabetic drug users in comparison to the control group. Moreover, there was no significant difference in biopsy tumor over-or under-grading.…”

“…30 On the other hand, two other large studies found a reduced mortality of PCa patients upon metformin use. 26,31 Although the anti-tumor effect of metformin has been observed in different types of cancers a clear mechanism of action remained elusive. To our best knowledge the present study is the first analyzing proposed molecular pathways of antidiabetic drugs in the prostate tissue of patients suffering from both PCa and DM.…”

The Effect of Metformin on Mortality Following Cancer among Patients with Diabetes

“…Sample sizes of diabetic patients ranged from 54 to 10,309 and percentage of metformin users ranged from 17.6% to 67.6%. One study included all cancer sites (21), four on breast (25)(26)(27)(28), colon (29)(30)(31)(32), and prostate cancers each (33)(34)(35)(36), two each on pancreatic (37,38) and endometrial cancers (39,40), and one study each on ovarian (41), liver (42), laryngeal (43), and lung cancers (44).…”

Esophageal Adenocarcinoma: The Influence of Medications Used to Treat Comorbidities on Cancer Prognosis

“…[101][102][103][104][105][106][107][108][109] The inconsistent findings across studies may be due to their retrospective design, inappropriate comparators or the use of exposure data from sources such as medical records and automated pharmacy databases.…”