Skip to main content

Advertisement

Log in

Diabetes and kidney cancer outcomes: a propensity score analysis

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

There is conflicting evidence whether diabetes is associated with survival outcomes in patients undergoing a nephrectomy for renal cell carcinoma. We performed a retrospective review of 1034 patients undergoing nephrectomy for unilateral, M0, renal cell carcinoma between 2000 and 2016 at a tertiary academic center. Inverse probability of treatment weights were derived from a propensity score model based on various clinical, surgical, and pathological characteristics. We used Cox proportional hazard models to evaluate the association between diabetes and disease-free survival, cancer-specific survival, and overall survival in the sample weighted by the inverse probability of treatment weights. Furthermore, to evaluate whether severity of diabetes was associated with survival outcomes, we performed separate analyses where inverse probability of treatment weights were computed based on the probability of having diabetes that was controlled by medication. Of the 1034 patients, 180 (17 %) had diabetes. Of these, 139 (77 %) patients required medications for diabetes control while the remaining 41 (23 %) had diet controlled diabetes. Median follow-up was 50 months (IQR 17–86). Diabetes at the time of surgery was not significantly associated with disease-free survival (HR 1.11, 95 % CI 0.64 –1.91), cancer-specific survival (HR 0.96, 95 % CI 0.49–1.91), or overall survival (HR 1.28, 95 % CI 0.84–1.95). We found similar results when we compared diabetics controlled with medication vs. non-diabetics or diet controlled diabetics. In summary, we found no significant association between diabetes and survival outcomes in patients undergoing nephrectomy for M0 renal cell carcinoma. These results suggest that diabetics should be treated and followed in a similar manner to non-diabetics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. International Agency for Research on Cancer, World Health Organization, GLOBOCAN: Estimated Cancer Incidence, Mortality, and Prevalence Worldwide in 2012, Lyon, France (IARC, 2014)

  2. A. Znaor, J. Lortet-Tieulent, M. Laversanne, A. Jemal, F. Bray, International variations and trends in renal cell carcinoma incidence and mortality. Eur. Urol. 67(3), 519–530 (2014)

  3. W.H. Chow, L.M. Dong, S.S. Devesa, Epidemiology and risk factors for kidney cancer. Nat. Rev. Urol. 7(5), 245–257 (2010). doi:10.1038/nrurol.2010.46

    Article  PubMed  PubMed Central  Google Scholar 

  4. S.C. Larsson, A. Wolk, Diabetes mellitus and incidence of kidney cancer: a meta-analysis of cohort studies. Diabetologia 54(5), 1013–1018 (2011). doi:10.1007/s00125-011-2051-6

    Article  CAS  PubMed  Google Scholar 

  5. C. Bao, X. Yang, W. Xu, H. Luo, Z. Xu, C. Su, X. Qi, Diabetes mellitus and incidence and mortality of kidney cancer: a meta-analysis. J. Diabetes Complications 27(4), 357–364 (2013). doi:10.1016/j.jdiacomp.2013.01.004

    Article  PubMed  Google Scholar 

  6. K.S. Peairs, B.B. Barone, C.F. Snyder, H.-C. Yeh, K.B. Stein, R.L. Derr, F.L. Brancati, A.C. Wolff, Diabetes mellitus and breast cancer outcomes: a systematic review and meta-analysis. J. Clin. Oncol. 29(1), 40–46 (2011)

    Article  PubMed  Google Scholar 

  7. Y. Jiang, Q. Ben, H. Shen, W. Lu, Y. Zhang, J. Zhu, Diabetes mellitus and incidence and mortality of colorectal cancer: a systematic review and meta-analysis of cohort studies. Eur. J. Epidemiol. 26(11), 863–876 (2011)

    Article  PubMed  Google Scholar 

  8. J.-Y. Lee, I. Jeon, J.M. Lee, J.-M. Yoon, S.M. Park, Diabetes mellitus as an independent risk factor for lung cancer: a meta-analysis of observational studies. Eur. J. Cancer 49(10), 2411–2423 (2013)

    Article  PubMed  Google Scholar 

  9. J.C. Will, F. Vinicor, E.E. Calle, Is diabetes mellitus associated with prostate cancer incidence and survival? Epidemiology 10(3), 313–318 (1999)

    Article  CAS  PubMed  Google Scholar 

  10. A. Antonelli, N. Arrighi, S. Corti, T. Zanotelli, A. Cozzoli, S. Cosciani Cunico, C. Simeone, Pre-existing type-2 diabetes is not an adverse prognostic factor in patients with renal cell carcinoma: a single-center retrospective study. Urol. Oncol. 31(7), 1310–1315 (2013). doi:10.1016/j.urolonc.2011.12.013

    Article  PubMed  Google Scholar 

  11. H. Chung, S. Chen, M. Li, Diabetes and risk of death from cancer of the prostate, kidney, and urinary bladder. Urology 74(4 Suppl S), S36–S37 (2009). doi:10.1016/j.urology.2009.07.1106

    Article  Google Scholar 

  12. S.S. Coughlin, J.D. Neaton, B. Randall, A. Sengupta, Predictors of mortality from kidney cancer in 332,547 men screened for the multiple risk factor intervention trial. Cancer 79(11), 2171–2177 (1997)

    Article  CAS  PubMed  Google Scholar 

  13. H. Fukushima, H. Masuda, M. Yokoyama, M. Tatokoro, S. Yoshida, J. Ishioka, Y. Matsuoka, N. Numao, F. Koga, K. Saito, Y. Fujii, K. Kihara, Diabetes mellitus with obesity is a predictor of recurrence in patients with non-metastatic renal cell carcinoma. Jpn. J. Clin. Oncol. 43(7), 740–746 (2013). doi:10.1093/jjco/hyt070

    Article  PubMed  Google Scholar 

  14. Y.S. Ha, W.T. Kim, S.J. Yun, S.C. Lee, W.J. Kim, Y.H. Park, S.H. Kang, S.H. Hong, S.S. Byun, Y.J. Kim, Multi-institutional analysis of localized renal cell carcinoma that demonstrates the impact of diabetic status on prognosis after nephrectomy. Ann. Surg. Oncol. 20(11), 3662–3668 (2013). doi:10.1245/s10434-013-3147-7

    Article  PubMed  Google Scholar 

  15. T. Höfner, M. Zeier, G. Hatiboglu, C. Eisen, G. Schönberg, B. Hadaschik, D. Teber, S. Duensing, A. Trumpp, M. Hohenfellner, The impact of type 2 diabetes on the outcome of localized renal cell carcinoma. World J. Urol. 32(6), 1537–1542 (2014)

    Article  PubMed  Google Scholar 

  16. S.H. Jee, H. Ohrr, J.W. Sull, J.E. Yun, M. Ji, J.M. Samet, Fasting serum glucose level and cancer risk in Korean men and women. JAMA 293(2), 194–202 (2005)

    Article  CAS  PubMed  Google Scholar 

  17. E.K. Lam, G.D. Batty, R.R. Huxley, A.L. Martiniuk, F. Barzi, T.H. Lam, C.M. Lawes, G.G. Giles, T. Welborn, H. Ueshima, A. Tamakoshi, J. Woo, H.C. Kim, X. Fang, S. Czernichow, M. Woodward, Asia Pacific Cohort Studies Collaboration: Associations of diabetes mellitus with site-specific cancer mortality in the Asia-Pacific region. Ann. Oncol. 22(3), 730–738 (2011). doi:10.1093/annonc/mdq405

    Article  CAS  PubMed  Google Scholar 

  18. Y.J. Lee, J. Suh, M. Kim, M.S. Choo, S.B. Lee, H. Jeong, K. Park, W.S. Choi, C.W. Jeong, J.H. Ku, H.H. Kim, C. Kwak, Is diabetes mellitus associated with cancer specific and overall survival in localized clear cell renal cell carcinoma? J. Urol. 1, e654 (2014). doi:10.1016/j.juro.2014.02.1808

    Article  Google Scholar 

  19. S. Steffens, C. Von Klot, H. Eggers, C. Seidel, G. Wegener, M. Schrader, M.A. Kuczyk, A.J. Schrader, The role of diabetes mellitus and obesity in localized and metastatic RCC. Eur. Urol. 11(1), e1018–e1018a (2012). Supplements

    Article  Google Scholar 

  20. E. Suer, E. Ozturk, O. Gulpinar, A. Kayis, S. Baltaci, Effect of type 2 diabetes mellitus on prognosis of nonmetastatic renal cell cancer. Korean J. Urol. 54(8), 499–503 (2013). doi:10.4111/kju.2013.54.8.499

    Article  PubMed  PubMed Central  Google Scholar 

  21. A. Vavallo, S. Simone, G. Lucarelli, M. Rutigliano, V. Galleggiante, G. Grandaliano, L. Gesualdo, M. Campagna, M. Cariello, E. Ranieri, G. Pertosa, G. Lastilla, F.P. Selvaggi, P. Ditonno, M. Battaglia, Pre-existing type 2 diabetes mellitus is an independent risk factor for mortality and progression in patients with renal cell carcinoma. Medicine 93(27), (2014). doi:10.1097/MD.0000000000000183

  22. M. Washio, M. Mori, K. Mikami, T. Miki, Y. Watanabe, M. Nakao, T. Kubo, K. Suzuki, K. Ozasa, K. Wakai, A. Tamakoshi, Cigarette smoking and other risk factors for kidney cancer death in a Japanese population: Japan Collaborative Cohort Study for evaluation of cancer risk (JACC study). Asian Pac. J. Cancer Prev. 14(11), 6523–6528 (2014)

    Article  PubMed  Google Scholar 

  23. X. Liu, J. Ji, K. Sundquist, J. Sundquist, K. Hemminki, The impact of type 2 diabetes mellitus on cancer-specific survival: a follow-up study in Sweden. Cancer 118(5), 1353–1361 (2012). doi:10.1002/cncr.26420

    Article  PubMed  Google Scholar 

  24. S.P. Psutka, S.B. Stewart, S.A. Boorjian, C.M. Lohse, M.K. Tollefson, J.C. Cheville, B.C. Leibovich, R.H. Thompson, Diabetes mellitus is independently associated with an increased risk of mortality in patients with clear cell renal cell carcinoma. J. Urol. (2014). doi:10.1016/j.juro.2014.06.014

  25. K. Ranc, M.E. Jørgensen, S. Friis, B. Carstensen, Mortality after cancer among patients with diabetes mellitus: effect of diabetes duration and treatment. Diabetologia 57(5), 927–934 (2014)

    Article  CAS  PubMed  Google Scholar 

  26. P.T. Campbell, C.C. Newton, A.V. Patel, E.J. Jacobs, S.M. Gapstur, Diabetes and cause-specific mortality in a prospective cohort of one million U.S. adults. Diabetes Care 35(9), 1835–1844 (2012). doi:10.2337/dc12-0002

    Article  PubMed  PubMed Central  Google Scholar 

  27. E. Clarke, L. Marrett, N. Kreiger, Appendix 3 (c) Cancer registration in Ontario: a computer approach. Cancer Reg. 95, 246–257 (1991)

    Google Scholar 

  28. D.R. Brenner, M.C. Tammemagi, S.B. Bull, D. Pinnaduwaje, I.L. Andrulis, Using cancer registry data: agreement in cause-of-death data between the Ontario Cancer Registry and a longitudinal study of breast cancer patients. Chronic Dis. Can. 30(1), 16–19 (2009)

    CAS  PubMed  Google Scholar 

  29. P.C. Austin, The use of propensity score methods with survival or time‐to‐event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat. Med. 33(7), 1242–1258 (2014)

    Article  PubMed  Google Scholar 

  30. M. Nayan, A. Finelli, M. Jewett, D. Juurlink, P. Austin, G. Kulkarni, R. Hamilton, Statin use and kidney cancer survival outcomes: a propensity score analysis. Urol. Oncol. (2016). doi:10.1016/j.urolonc.2016.06.007

  31. C.L. Atzema, K. Grewal, H. Lu, M.K. Kapral, G. Kulkarni, P.C. Austin, Outcomes among patients discharged from the emergency department with a diagnosis of peripheral vertigo. Ann. Neurol. (2015)

  32. P.C. Austin, M.M. Mamdani, A comparison of propensity score methods: a case‐study estimating the effectiveness of post‐AMI statin use. Stat. Med. 25(12), 2084–2106 (2006)

    Article  PubMed  Google Scholar 

  33. P.C. Austin, E.A. Stuart, Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat. Med. 34(28), 3661–3679 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  34. M.A. Brookhart, R. Wyss, J.B. Layton, T. Stürmer, Propensity score methods for confounding control in nonexperimental research. Circulation 6(5), 604–611 (2013)

    PubMed  PubMed Central  Google Scholar 

  35. P.C. Austin, Optimal caliper widths for propensity‐score matching when estimating differences in means and differences in proportions in observational studies. Pharm. Stat. 10(2), 150–161 (2011)

    Article  PubMed  Google Scholar 

  36. P.C. Austin, Assessing balance in measured baseline covariates when using many‐to‐one matching on the propensity‐score. Pharmacoepidemiol. Drug Saf. 17(12), 1218–1225 (2008)

    Article  PubMed  Google Scholar 

  37. P.C. Austin, Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat. Med. 28, 3083–3107 (2009)

    Article  PubMed  PubMed Central  Google Scholar 

  38. S.R. Cole, M.A. Hernán, Adjusted survival curves with inverse probability weights. Comput. Methods Programs Biomed. 75(1), 45–49 (2004)

    Article  PubMed  Google Scholar 

  39. P.C. Austin, T. Schuster, The performance of different propensity score methods for estimating absolute effects of treatments on survival outcomes: a simulation study. Stat. Methods Med. Res. 25(5), 2214–2237 (2014)

  40. D.Y. Lin, L.-J. Wei, Z. Ying, Checking the Cox model with cumulative sums of martingale-based residuals. Biometrika 80(3), 557–572 (1993)

    Article  Google Scholar 

  41. L. Chen, H. Li, L. Gu, X. Ma, X. Li, Y. Gao, Y. Zhang, D. Shen, Y. Fan, B. Wang, The impact of diabetes mellitus on renal cell carcinoma prognosis: a meta-analysis of cohort studies. Medicine 94(26), e1055 (2015)

  42. R.D. Riley, J.P. Higgins, J.J. Deeks, Interpretation of random effects meta-analyses. BMJ 342, d549 (2011). doi:10.1136/bmj.d549

    Article  PubMed  Google Scholar 

  43. R. Novosyadlyy, D.E. Lann, A. Vijayakumar, A. Rowzee, D.A. Lazzarino, Y. Fierz, J.M. Carboni, M.M. Gottardis, P.A. Pennisi, A.A. Molinolo, Insulin-mediated acceleration of breast cancer development and progression in a nonobese model of type 2 diabetes. Cancer Res. 70(2), 741–751 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. A. Grothey, W. Voigt, C. Schöber, T. Müller, W. Dempke, H. Schmoll, The role of insulin-like growth factor I and its receptor in cell growth, transformation, apoptosis, and chemoresistance in solid tumors. J. Cancer Res. Clin. Oncol. 125(3–4), 166–173 (1999)

    Article  CAS  PubMed  Google Scholar 

  45. R. Baserga, F. Peruzzi, K. Reiss, The IGF-1 receptor in cancer biology. Int. J. Cancer 107(6), 873–877 (2003). doi:10.1002/ijc.11487

    Article  CAS  PubMed  Google Scholar 

  46. M. Nayan, B. Bhindi, L.Y. Julie, T. Hermanns, A. Mohammed, R. J. Hamilton, A. Finelli, M.A. Jewett, A.R. Zlotta, N.E. Fleshner, The effect of metformin on cancer-specific survival outcomes in diabetic patients undergoing radical cystectomy for urothelial carcinoma of the bladder. Urol. Oncol. 33(9), 386.e7–13 (2015). doi:10.1016/j.urolonc.2015.05.024

  47. D. Margel, D.R. Urbach, L.L. Lipscombe, C.M. Bell, G. Kulkarni, P.C. Austin, N. Fleshner, Metformin use and all-cause and prostate cancer-specific mortality among men with diabetes. J. Clin. Oncol. 31(25), 3069–3075 (2013). doi:10.1200/JCO.2012.46.7043

    Article  CAS  PubMed  Google Scholar 

  48. N. Sadeghi, J.L. Abbruzzese, S.-C.J. Yeung, M. Hassan, D. Li, Metformin use is associated with better survival of diabetic patients with pancreatic cancer. Clin. Cancer Res. 18(10), 2905–2912 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. M. Nayan, A. Finelli, M.A. Jewett, D.N. Juurlink, P.C. Austin, G.S. Kulkarni, R.J. Hamilton, Metformin use and kidney cancer outcomes in patients with diabetes: a propensity score analysis. Clin. Genitourin. Cancer (2016). doi:10.1016/j.clgc.2016.06.008

  50. A.A. Hakimi, L. Chen, P.H. Kim, D. Sjoberg, L. Glickman, M.R. Walker, P. Russo, The impact of metformin use on recurrence and cancer-specific survival in clinically localized high-risk renal cell carcinoma. Can. Urol. Assoc. J. 7(11–12), E687–E691 (2013). doi:10.5489/cuaj.1447

    Article  PubMed  PubMed Central  Google Scholar 

  51. S.P. Psutka, S.A. Boorjian, C.M. Lohse, S.B. Stewart, M.K. Tollefson, J.C. Cheville, B.C. Leibovich, R.H. Thompson, The association between metformin use and oncologic outcomes among surgically treated diabetic patients with localized renal cell carcinoma. Urol. Oncol. 33(2), 67.e15–23. doi:10.1016/j.urolonc.2014.07.008

  52. M. Nayan, E.M. Macdonald, D.N. Juurlink, P.C. Austin, A. Finelli, G.S. Kulkarni, R.J. Hamilton, Medication use and survival in diabetic patients with kidney cancer: a population-based cohort study. Pharmacol. Res. 113, 468–474 (2016). doi:10.1016/j.phrs.2016.09.027

  53. I. Frank, M.L. Blute, J.C. Cheville, C.M. Lohse, A.L. Weaver, H. Zincke, An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J. Urol. 168(6), 2395–2400 (2002)

    Article  PubMed  Google Scholar 

  54. L.V. van de Poll-Franse, S. Houterman, M.L. Janssen-Heijnen, M.W. Dercksen, J.W. Coebergh, H.R. Haak, Less aggressive treatment and worse overall survival in cancer patients with diabetes: a large population based analysis. Int. J. Cancer 120(9), 1986–1992 (2007). doi:10.1002/ijc.22532

    Article  PubMed  Google Scholar 

Download references

Funding

This study did not receive funding.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robert J. Hamilton.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nayan, M., Finelli, A., Jewett, M.A.S. et al. Diabetes and kidney cancer outcomes: a propensity score analysis. Endocrine 55, 470–477 (2017). https://doi.org/10.1007/s12020-016-1149-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-016-1149-5

Keywords

Navigation