Evaluation of the prognostic role of co-morbidities on disease outcome in renal cell carcinoma patients



Co-morbidities may induce local and systemic tumor progression of renal cell carcinoma (RCC); however, the prognostic impact of co-morbidities has not yet been well characterized.

Patients and methods

RCC patients (n = 2206) surgically treated at three academic institutions in the US and Europe were included in the analysis. Presence of diabetes mellitus, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, coronary heart disease, and hypothyroidism were investigated for their association with clinicopathological features and cancer-specific survival.


Hypertension was associated with less advanced T stages (p = 0.025), a lower risk of lymph-node (p = 0.026) and distant metastases (p = 0.001), and improved cancer specific survival in univariable analysis (HR 0.81 95% CI 0.69–0.96, p = 0.013). However, hypertension was not an independent prognostic factor after adjustment for TNM stages, grading, and ECOG performance status (HR 0.95, 95% CI 0.80–1.12; p = 0.530). A correlation between the use of concomitant anti-hypertensive medications and improved survival outcome was not identified. All other investigated co-morbidities did not show significant associations with clinicopathological features or cancer-specific survival.


Although the investigated co-morbidities are capable or inducing pathophysiological changes that are predisposing factors for tumor progression, none is an independent prognostic factor in patients with RCC.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. 1.

    Klatte T, Rossi SH, Stewart GD (2018) Prognostic factors and prognostic models for renal cell carcinoma: a literature review. World J Urol 36:1943–1952

    Article  Google Scholar 

  2. 2.

    Mitchell TJ, Rossi SH, Klatte T, Stewart GD (2018) Genomics and clinical correlates of renal cell carcinoma. World J Urol 36:1899–1911

    CAS  Article  Google Scholar 

  3. 3.

    Barata PC, Rini BI (2017) Treatment of renal cell carcinoma: current status and future directions. CA Cancer J Clin 67:507–524

    Article  Google Scholar 

  4. 4.

    Birkhäuser F, Kroeger N, Pantuck A (2012) Etiology of RCC: incidence, demographics, and environmental factors. In: Rini B, Campbell S (eds) Renal cell carcinoma: clinical management, vol 1. Springer, New York, pp 3–22

    Google Scholar 

  5. 5.

    Cooper DS (2003) Hyperthyroidism. Lancet 362:459–468

    CAS  Article  Google Scholar 

  6. 6.

    Kent BD, Mitchell PD, McNicholas WT (2011) Hypoxemia in patients with COPD: cause, effects, and disease progression. Int J Chron Obstruct Pulmon Dis 6:199–208

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Tecklenborg J, Clayton D, Siebert S, Coley SM (2018) The role of the immune system in kidney disease. Clin Exp Immunol 192:142–150

    CAS  Article  Google Scholar 

  8. 8.

    Belldegrun AS, Klatte T, Shuch B, LaRochelle JC, Miller DC, Said JW, Riggs SB, Zomorodian N, Kabbinavar FF, Dekernion JB, Pantuck AJ (2008) Cancer-specific survival outcomes among patients treated during the cytokine era of kidney cancer (1989–2005): a benchmark for emerging targeted cancer therapies. Cancer 113:2457–2463

    Article  Google Scholar 

  9. 9.

    Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B, CheckMate I (2018) Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 378:1277–1290

    CAS  Article  Google Scholar 

  10. 10.

    Ljungberg B, Bensalah K, Canfield S, Dabestani S, Hofmann F, Hora M, Kuczyk MA, Lam T, Marconi L, Merseburger AS, Mulders P, Powles T, Staehler M, Volpe A, Bex A (2015) EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol 67:913–924

    Article  Google Scholar 

  11. 11.

    Bedke J, Heide J, Ribback S, Rausch S, de Martino M, Scharpf M, Haitel A, Zimmermann U, Pechoel M, Alkhayyat H, Shariat SF, Dombrowski F, Stenzl A, Burchardt M, Klatte T, Kroeger N (2018) Microvascular and lymphovascular tumour invasion are associated with poor prognosis and metastatic spread in renal cell carcinoma: a validation study in clinical practice. BJU Int 121:84–92

    CAS  Article  Google Scholar 

  12. 12.

    Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649–655

    CAS  Article  Google Scholar 

  13. 13.

    Fuhrman S, Lasky L, Limas C (1982) Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 6:655–663

    CAS  Article  Google Scholar 

  14. 14.

    Kroeger N, Rampersaud EN, Patard JJ, Klatte T, Birkhauser FD, Shariat SF, Lang H, Rioux-Leclerq N, Remzi M, Zomorodian N, Kabbinavar FF, Belldegrun AS, Pantuck AJ (2012) Prognostic value of microvascular invasion in predicting the cancer specific survival and risk of metastatic disease in renal cell carcinoma: a multicenter investigation. J Urol 187:418–423

    Article  Google Scholar 

  15. 15.

    Patard JJ, Leray E, Cindolo L, Ficarra V, Rodriguez A, De La Taille A, Tostain J, Artibani W, Abbou CC, Guille F, Chopin DK, Lobel B (2004) Multi-institutional validation of a symptom based classification for renal cell carcinoma. J Urol 172:858–862

    Article  Google Scholar 

  16. 16.

    Volzke H, Ludemann J, Robinson DM, Spieker KW, Schwahn C, Kramer A, John U, Meng W (2003) The prevalence of undiagnosed thyroid disorders in a previously iodine-deficient area. Thyroid 13:803–810

    Article  Google Scholar 

  17. 17.

    Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE (2002) Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 87:489–499

    CAS  Article  Google Scholar 

  18. 18.

    Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30

    Article  Google Scholar 

  19. 19.

    Macnee W (2007) Pathogenesis of chronic obstructive pulmonary disease. Clin Chest Med 28(479–513):v

    Google Scholar 

  20. 20.

    Ribback S, Cigliano A, Kroeger N, Pilo MG, Terracciano L, Burchardt M, Bannasch P, Calvisi DF, Dombrowski F (2015) PI3K/AKT/mTOR pathway plays a major pathogenetic role in glycogen accumulation and tumor development in renal distal tubules of rats and men. Oncotarget 6:13036–13048

    Article  Google Scholar 

  21. 21.

    Weikert S, Ljungberg B (2010) Contemporary epidemiology of renal cell carcinoma: perspectives of primary prevention. World J Urol 28:247–252

    Article  Google Scholar 

  22. 22.

    Psutka SP, Stewart SB, Boorjian SA, Lohse CM, Tollefson MK, Cheville JC, Leibovich BC, Thompson RH (2014) Diabetes mellitus is independently associated with an increased risk of mortality in patients with clear cell renal cell carcinoma. J Urol 192:1620–1627

    Article  Google Scholar 

  23. 23.

    Steffens S, Von Klot C, Eggers H, Seidel C, Wegener G, Schrader M, Kuczyk MA, Schrader AJ, Network GRC (2012) The role of diabetes mellitus and obesity in localized and metastatic RCC. Eur Urol Suppl 11:E1018–U1130

    Article  Google Scholar 

  24. 24.

    Neuzillet Y, Tillou X, Mathieu R, Long JA, Gigante M, Paparel P, Poissonnier L, Baumert H, Escudier B, Lang H, Rioux-Leclercq N, Bigot P, Bernhard JC, Albiges L, Bastien L, Petit J, Saint F, Bruyere F, Boutin JM, Brichart N, Karam G, Branchereau J, Ferriere JM, Wallerand H, Barbet S, Elkentaoui H, Hubert J, Feuillu B, Theveniaud PE, Villers A, Zini L, Descazeaux A, Roupret M, Barrou B, Fehri K, Lebret T, Tostain J, Terrier JE, Terrier N, Martin L, Dugardin F, Galliot I, Staerman F, Azemar MD, Irani J, Tisserand B, Timsit MO, Sallusto F, Rischmann P, Guy L, Valeri A, Deruelle C, Azzouzi AR, Chautard D, Mejean A, Salomon L, Rigaud J, Pfister C, Soulie M, Kleinclauss F, Badet L, Patard JJ, Francais CCA (2011) Renal cell carcinoma (RCC) in patients with end-stage renal disease exhibits many favourable clinical, pathologic, and outcome features compared With RCC in the general population. Eur Urol 60:366–373

    Article  Google Scholar 

  25. 25.

    Lane BR, Campbell SC, Demirjian S, Fergany AF (2013) Surgically induced chronic kidney disease may be associated with a lower risk of progression and mortality than medical chronic kidney disease. J Urol 189:1649–1655

    Article  Google Scholar 

  26. 26.

    Kroeger N, Klatte T, Chamie K, Rao PN, Birkhäuser FD, Sonn GA, Riss J, Kabbinavar FF, Belldegrun AS, Pantuck AJ (2013) Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma. Cancer 119:1547–1554

    CAS  Article  Google Scholar 

  27. 27.

    Smyth LJ, Duffy S, Maxwell AP, McKnight AJ (2014) Genetic and epigenetic factors influencing chronic kidney disease. Am J Physiol Renal 307:F757–F776

    CAS  Article  Google Scholar 

  28. 28.

    Schmidinger M, Vogl UM, Bojic M, Lamm W, Heinzl H, Haitel A, Clodi M, Kramer G, Zielinski CC (2011) Hypothyroidism in patients with renal cell carcinoma: blessing or curse? Cancer 117:534–544

    Article  Google Scholar 

  29. 29.

    Hegemann M, Kroeger N, Stenzl A, Bedke J (2018) Rare and changeable as a chameleon: paraneoplastic syndromes in renal cell carcinoma. World J Urol 36:849–854

    CAS  Article  Google Scholar 

  30. 30.

    Capitanio U, Bensalah K, Bex A, Boorjian SA, Bray F, Coleman J, Gore JL, Sun M, Wood C, Russo P (2019) Epidemiology of renal cell carcinoma. Eur Urol 75:74–84

    Article  Google Scholar 

  31. 31.

    McKay RR, Rodriguez GE, Lin X, Kaymakcalan MD, Hamnvik OP, Sabbisetti VS, Bhatt RS, Simantov R, Choueiri TK (2015) Angiotensin system inhibitors and survival outcomes in patients with metastatic renal cell carcinoma. Clin Cancer Res 21:2471–2479

    CAS  Article  Google Scholar 

  32. 32.

    Palapattu GS, Kristo B, Rajfer J (2002) Paraneoplastic syndromes in urologic malignancy: the many faces of renal cell carcinoma. Rev Urol 4:163–170

    PubMed  PubMed Central  Google Scholar 

  33. 33.

    Rini BI, Cohen DP, Lu DR, Chen I, Hariharan S, Gore ME, Figlin RA, Baum MS, Motzer RJ (2011) Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst 103:763–773

    CAS  Article  Google Scholar 

  34. 34.

    Rini BI, Melichar B, Fishman MN, Oya M, Pithavala YK, Chen Y, Bair AH, Grunwald V (2015) Axitinib dose titration: analyses of exposure, blood pressure and clinical response from a randomized phase II study in metastatic renal cell carcinoma. Ann Oncol 26:1372–1377

    CAS  Article  Google Scholar 

  35. 35.

    Rossi SH, Klatte T, Usher-Smith J, Stewart GD (2018) Epidemiology and screening for renal cancer. World J Urol 36:1341–1353

    Article  Google Scholar 

Download references

Author information




Study design: NK, TK, and AJP. Writing of the manuscript: JH, TK, AJP, and NK. Statistical analyses: NK and TK. Data interpretation: all authors. Collection of data: all authors. Interpretation of analyses: all authors. Approval of the manuscript: all authors.

Corresponding author

Correspondence to Nils Kroeger.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 128 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Heide, J., Ribback, S., Klatte, T. et al. Evaluation of the prognostic role of co-morbidities on disease outcome in renal cell carcinoma patients. World J Urol 38, 1525–1533 (2020). https://doi.org/10.1007/s00345-019-02930-4

Download citation


  • Renal cell carcinoma
  • Co-morbidities
  • Hypertension
  • Co-morbidities
  • Anti-hypertensive medication
  • Statins
  • Prognostic factors