e16553 Background: Prostate cancer (PC) is the most common non-cutaneous cancer in men and the third most common cause of cancer death in males. Several studies have shown that use of commonly prescribed medications, is associated with improved survival in various malignancies, including PC. There has not been any large population-based study, examining the effects of these and other commonly prescribed medications, such as proton pump inhibitors (PPI), on the rate of PC diagnosis, PC advanced disease and PC-specific death. Methods: A retrospective population-based study using data from the institute of clinical evaluative sciences, including all male patients aged 65 and above in Ontario who have had a negative first prostate biopsy between 1994 and 2016. We assessed the impact of commonly prescribed medications on PC outcomes. The analyzed medications included Statins (hydrophilic and hydrophobic), most commonly used diabetes drugs (metformin, insulins, sulfonylureas, and thizolidinedions), PPIs, 5 alpha reductase inhibitors, and alpha blockers. Time dependent Cox regression proportional hazards models were performed to determine predictors of PC diagnosis, PC advanced disease (defined as usage of hormonal therapy), and PC-specific death. Medication exposure was time varying and modelled as “ever” vs. “never” use or as cumulative exposure. Results: A total of 21,562 men were analyzed over a mean (SD) follow-up time of 8.06 (5.44) years. Overall, 5,187 patients (24%) were diagnosed with PC, 7861 (36.5%) had died, and 647 (3%) died of PC. On multivariable analysis usage of hydrophilic statins modelled as “ever vs. never” was associated with a lower diagnosis rate (OR 0.832, 95% CI 0.732-0.946, p = 0.005) and a significantly decreased PC-specific death (OR 0.676, 95% CI 0.528-0.871, p = 0.0024). In contrast, Pantoprazole was associated with a higher rate of advanced PC disease when modelled as cumulative exposure of 6 months (OR 1.03, 95% CI 1.003-1.06, P = 0.031), and PC-specific death, when modeled as “ever vs. never” (OR 1.26, 95% CI 1.02-1.576, p = 0.031). Conclusions: Hydrophilic statins were associated with a clinically and statistically significant lower PC diagnosis and PC-specific death, while pantoprazole was associated with a higher rate of advanced PC disease and PC-specific death.
309 Background: Proton pump inhibitors (PPIs) are a commonly prescribed class of medications. Although in-vitro and in-vivo data have shown PPIs to have anti-tumor effects, more recent studies suggest an increased cancer risk in several solid organs. Pantoprazole, a commonly prescribed PPI, has been shown to harbor a protective effect in human prostate cancer (PCa) cells. We aimed to investigate the effect of pantoprazole and other PPIs on PCa-specific death and additional PCa outcomes. Methods: In this retrospective, population-based cohort study, data were incorporated from the Institute for Clinical and Evaluative Sciences to identify all men aged 66 and above with a history of a single negative prostate biopsy between 1994 and 2016. We used multivariable Cox regression models with time-dependent covariates, to assess the effect of PPIs on PCa diagnosis, androgen deprivation therapy (ADT) use, and PCa-specific death. All models included other medications with a putative effect on PCa. All models were adjusted for age, rurality, comorbidity, and year of patient study inclusion. Results: Overall, 21,512 men were included, with a mean follow-up time of 8.06 years (SD 5.44 years). A total of 10,999 patients (51.1%) used a PPI. A total of 5,187 patients (24.1%) were diagnosed with PCa, 2,043 patients (9.5%) were treated with ADT, and 805 patients (3.7%) died from PCa. Pantoprazole was associated with a 3.0% (95% CI 0.3%-6,0%) increased rate of being treated with ADT for every six months of cumulative use, while any use of all other PPIs was associated with a 39.0% (95% CI 18.0%-64.0%) increased PCa-specific mortality. No significant association was found with PCa diagnosis. Conclusions: Upon validation of the potentially negative association of PPIs with PCa outcomes, the expansive use of PPIs may need to be reassessed, especially in PCa patients.
40 Background: Prostate cancer (PC) is the most common non-cutaneous cancer in Canadian men and the third most common cause of cancer death in Canada. Several studies have shown that use of commonly prescribed medications, including those used for diabetes and hypercholesterolemia, is associated with improved survival in various malignancies, including PC. There has not been any large population-based study, examining the effects of these and other commonly prescribed medications, on the rate of PC diagnosis, over a 20 years follow-up period. Methods: A retrospective population-based study using data from the institute of clinical evaluative sciences, including all male patients aged 65 and above in Ontario who have had a negative first prostate biopsy between 1994 and 2016. We assessed the impact of commonly prescribed medications on PC diagnosis. The medications included Statins (hydrophilic and hydrophobic), diabetes drugs (metformin, insulins, sulfonylureas, and thizolidinedions), proton pump inhibitors, 5 alpha reductase inhibitors, and alpha blockers. Time dependent Cox regression proportional hazards models were performed determine predictors of PC diagnosis. Medication exposure was time varying and modeled as “ever” vs. “never” use or as cumulative exposure for 6 months of usage. A priori variables included in the model included age, ADG comorbidity score, rurality index, index year, and all medications. Results: A total of 51,415 men were analyzed over a mean (SD) follow-up time of 8.06 (5.44) years. Overall, 10,466 patients (20.4%) were diagnosed with PC, 16,726 (32.5%) had died, and 1,460 (2.8%) patients died of PC. On multivariable analysis increasing age and rurality index were associated with higher PC diagnosis rate, while a more recent index year, and usage of hydrophilic statins was associated with a lower diagnosis rate in both “ever” vs. “never” and cumulative models (HR 0.832, 95% CI 0.732-0.946, p = 0.005, HR 0.973 95% CI 0.951-0.995, p = 0.016, respectively). Conclusions: Hydrophilic statins are associated with a clinically significant lower PC diagnosis. To our knowledge this is the first study demonstrating a clear advantage of one group of statins (hydrophilic) over another (hydrophobic) in PC prevention.
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