OJU  Vol.2 No.1 , February 2012
The Effect of Obesity and Diabetes on Intermediate to High Grade Prostate Cancer Patients Treated with Radical Prostatectomy
Abstract: Aims: The relationships between obesity, diabetes and prostate cancer are unclear. A retrospective study was performed to determine the effects of body mass index (BMI) and diabetes on patients with intermediate to high grade prostate cancer treated with radical prostatectomy. Methods: We reviewed 582 patients with Gleason score ≥ 7 non-metastatic prostate cancer treated with radical prostatectomy. Patients were stratified by BMI. End points were biochemical failure free survival (BFFS), overall survival (OS), and cancer specific survival (CSS). Results: Mean pre-treatment PSA decreased with increasing BMI (12.5, 7.6, 7.8 and 5.3 ng/mL with BMI < 25, 25 - 30, 30 - 35, and > 35, respectively; p < 0.001). There was no significant difference in BFFS, OS or CSS between diabetic and non-diabetic patients. After adjusting for potential confounders (age, Gleason score and pre-treatment PSA), patients with higher BMI experienced biochemical failure more often with hazard ratios 1.87 (1.15, 3.04; p = 0.01), 2.23 (1.39, 3.56; p < 0.001), and 2.5 (1.22, 5.12; p = 0.01) for BMI 25 - 30, 30 - 35 and > 35, respectively. However, for overall mortality the adjusted hazard ratio was 0.39 (0.18, 0.82; p = 0.01) for overweight patients (BMI 25 - 30) compared to patients with a BMI in the normal range. Patients with a BMI of 30 - 35 and > 35 had increased rates of positive margins than those with a BMI of 25 - 30 or < 25 (41.4% and 45.5% versus 28.9% and 33.3%, respectively; p = 0.02). Patients with higher BMI than 25 had higher biochemical recurrence rate (25 - 30 HR 2; 30 - 35 HR 1.97 and > 35 2.04) on multivariate analysis, margin positivity alone was not a significant factor. Conclusions: Patients with increasing BMI tend to have a lower PSA at diagnosis but are more likely to have biochemical failure after radical prostatectomy. In our cohort, this was not due to the increased incidence of positive margins. Having diabetes had no effect.
Cite this paper: E. H. Ramahi, K. C. Ansley, G. P. Swanson, F. Du and J. W. Basler, "The Effect of Obesity and Diabetes on Intermediate to High Grade Prostate Cancer Patients Treated with Radical Prostatectomy," Open Journal of Urology, Vol. 2 No. 1, 2012, pp. 20-27. doi: 10.4236/oju.2012.21005.

[1]   A. Jemal, R. Siegel, J. Xu and E. Ward, “Cancer Statistics, 2010,” Cancer Journal for Clinicians, Vol. 60, No. 5, 2010, pp. 277-300. doi:10.3322/caac.20073

[2]   K. M. Flegal, M. D. Carroll, C. L. Ogden and L. R. Curtin, “Prevalence and Trends in Obesity among US Adults, 1999-2008,” Journal of the American Medical Association, Vol. 303, No. 3, 2010, pp. 235-241. doi:10.1001/jama.2009.2014

[3]   E. E. Calle, C. Rodriguez, K. Walker-Thurmond and M. J. Thun, “Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults,” The New England Journal of Medicine, Vol. 348, No. 17, 2003, pp. 1625-1638. doi:10.1056/NEJMoa021423

[4]   R. G. Rogers, R. A. Hummer and P. M. Krueger, “The Effect of Obesity on Overall, Circulatory Disease- and Diabetes-Specific Mortality,” Journal of Biosocial Science, Vol. 35, No. 1, 2003, pp. 107-129. doi:10.1017/S002193200300107X

[5]   A. R. Kristal and Z. Gong, “Obesity and Prostate Cancer Mortality,” Future Oncology, Vol. 3, No. 5, 2007, pp. 557-567. doi:10.2217/14796694.3.5.557

[6]   P. Dimitropoulou, R. M. Martin, E. L. Turner, et al., “Association of Obesity with Prostate Cancer: A Case-Control Study within the Population-Based PSA Testing Phase of the Protect Study,” British Journal of Cancer, Vol. 104, No. 5, 2011, pp. 875-881. doi:10.1038/sj.bjc.6606066

[7]   J. A. Efstathiou, K. Bae, W. U. Shipley, et al., “Obesity and Mortality in Men with Locally Advanced Prostate Cancer: Analysis of RTOG 85-31,” Cancer, Vol. 110, No. 12, 2007, pp. 2691-2699. doi:10.1002/cncr.23093

[8]   B. J. Davies, M. C. Smaldone, N. Sadetsky, et al., “The Impact of Obesity on Overall and Cancer Specific Survival in Men with Prostate Cancer,” Journal of Urology, Vol. 182, No. 1, 2009, pp. 112-117. doi:10.1016/j.juro.2009.02.118

[9]   J. Pfitzenmaier, M. Pritsch, A. Haferkamp, et al., “Is the Body Mass Index a Predictor of Adverse Outcome in Prostate Cancer after Radical Prostatectomy in a Mid- European Study Population?” British Journal of Urology International, Vol. 103, No. 7, 2009, pp. 877-882. doi:10.1111/j.1464-410X.2008.08149.x

[10]   S. Bonovas, V. Peponis and K. Filioussi, “Diabetes Mellitus as a Risk Factor for Primary Open-Angle Glaucoma: A Meta-Analysis,” Diabetic Medicine, Vol. 21, No. 6, 2004, pp. 609-614. doi:10.1111/j.1464-5491.2004.01173.x

[11]   J. S. Kasper and E. Giovannucci, “A Meta-Analysis of Diabetes Mellitus and the Risk of Prostate Cancer,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 15, No. 11, 2006, pp. 2056-2062. doi:10.1158/1055-9965.EPI-06-0410

[12]   E. A. Atchison, G. Gridley, J. D. Carreon, et al., “Risk of Cancer in a Large Cohort of U.S. Veterans with Diabetes,” International Journal of Cancer, Vol. 128, No. 3, 2011, pp. 635-643. doi:10.1002/ijc.25362

[13]   T. Patel, G. Hruby, K. Badani, et al., “Clinical Outcomes after Radical Prostatectomy in Diabetic Patients Treated with Metformin,” Urology, Vol. 76, No. 5, 2010, pp. 1240-1244. doi:10.1016/j.urology.2010.03.059

[14]   J. M. Evans, L. A. Donnelly, A. M. Emslie-Smith, et al., “Metformin and Reduced Risk of Cancer in Diabetic Patients,” British Medical Journal, Vol. 330, No. 7503, 2005, pp. 1304-1305. doi:10.1136/bmj.38415.708634.F7

[15]   M. S. Cookson, G. Aus, A. L. Burnett, et al., “Variation in the Definition of Biochemical Recurrence in Patients Treated for Localized Prostate Cancer: The American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel Report and Recommendations for a Standard in the Reporting of Surgical Outcomes,” Journal of Urology, Vol. 177, No. 2, 2007, pp. 540-545. doi:10.1016/j.juro.2006.10.097

[16]   L. L. Banez, L. Sun, B. J. Trock, et al., “Body Mass Index and Prostate Specific Antigen as Predictors of Adverse Pathology and Biochemical Recurrence after Prostatectomy,” Journal of Urology, Vol. 182, No. 2, 2009, pp. 491-496. doi:10.1016/j.juro.2009.04.007

[17]   J. Baillargeon, B. H. Pollock, A. R. Kristal, et al., “The Association of Body Mass Index and Prostate-Specific Antigen in a Population-Based Study,” Cancer, Vol. 103, No. 5, 2005, pp. 1092-1095. doi:10.1002/cncr.20856

[18]   C. J. Kane, W. W. Bassett, N. Sadetsky, et al., “Obesity and Prostate Cancer Clinical Risk Factors at Presentation: Data from CaPSURE,” Journal of Urology, Vol. 173, No. 3, 2005, pp. 732-736. doi:10.1097/01.ju.0000152408.25738.23

[19]   N. Parekh, Y. Lin, R. S. Dipaola, et al., “Obesity and Prostate Cancer Detection: Insights from Three National Surveys,” American Journal of Medicine, Vol. 123, No. 9, 2010, pp. 829-835. doi:10.1016/j.amjmed.2010.05.011

[20]   L. L. Banez, R. J. Hamilton, A. W. Partin, et al., “Obesity-Related Plasma Hemodilution and PSA Concentration among Men with Prostate Cancer,” Journal of the American Medical Association, Vol. 298, No. 19, 2007, pp. 2275-2280. doi:10.1001/jama.298.19.2275

[21]   R. L. Grubb, A. Black, G. Izmirlian, et al., “Serum Prostate-Specific Antigen Hemodilution among Obese Men Undergoing Screening in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 18, No. 3, 2009, pp. 748-751. doi:10.1158/1055-9965.EPI-08-0938

[22]   S. Culp and M. Porter, “The Effect of Obesity and Lower Serum Prostate-Specific Antigen Levels on Prostate-Cancer Screening Results in American Men,” British Journal of Urology International, Vol. 104, No. 10, 2009, pp. 1457-1461. doi:10.1111/j.1464-410X.2009.08646.x

[23]   B. J. Davies, T. J. Walsh, P. L. Ross, et al., “Effect of BMI on Primary Treatment of Prostate Cancer,” Urology, Vol. 72, No. 2, 2008, pp. 406-411. doi:10.1016/j.urology.2007.11.032

[24]   J. Jayachandran, W. J. Aronson, M. K. Terris, et al., “Obesity and Positive Surgical Margins by Anatomic Location after Radical Prostatectomy: Results from the Shared Equal Access Regional Cancer Hospital Database,” British Journal of Urology International, Vol. 102, No. 8, 2008, pp. 964-968. doi:10.1111/j.1464-410X.2008.07881.x

[25]   J. S. Kasper, Y. Liu, M. N. Pollak, et al., “Hormonal Profile of Diabetic Men and the Potential Link to Prostate Cancer,” Cancer Causes Control, Vol. 19, No. 7, 2008, pp. 703-710. doi:10.1007/s10552-008-9133-x

[26]   I. Ben Sahra, K. Laurent, S. Giuliano, et al., “Targeting Cancer Cell Metabolism: The Combination of Metformin and 2-Deoxyglucose Induces p53-Dependent Apoptosis in Prostate Cancer Cells,” Cancer Research, Vol. 70, No. 6, 2010, pp. 2465-2475. doi:10.1158/0008-5472.CAN-09-2782

[27]   A. Decensi, M. Puntoni, P. Goodwin, et al., “Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-Analysis,” Cancer Prevention Research, Vol. 3, No. 11, 2010, pp. 1451-1461. doi:10.1158/1940-6207.CAPR-10-0157

[28]   C. J. Currie, C. D. Poole and E. A. Gale, “The Influence of Glucose-Lowering Therapies on Cancer Risk in Type 2 Diabetes,” Diabetologia, Vol. 52, No. 9, 2009, pp. 1766- 1777. doi:10.1007/s00125-009-1440-6