Impact of statin on renal cell carcinoma patients undergoing nephrectomy. Does it affect cancer progression and improves survival? A Systematic Review and Meta-Analysis


Published: October 4, 2023
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Introduction: Renal cell carcinoma (RCC) is regarded as one of the most common malignant tumors. Various concomitant medications in RCC patients undergoing surgery are investigated to explore the potential for improving survival and preventing disease recurrence, including statin. It has been observed that these drugs induce apoptosis, thereby inhibiting tumor growth and angiogenesis. We aimed to perform a systematic review and meta-analysis to enhance the level of evidence for statin in RCC. Methods: A systematic literature search was conducted in several online databases, including PubMed, Scopus, and Sciencedirect, using terms relevant to the use of statins in RCC patients undergoing nephrectomy for publications published up to July 2023, according to a registered review procedure (CRD42023452318). The Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias of the included study. Review Manager 5.4 was used for all analyses. Results: Seven articles was eligible for our study. The analysis revealed that patients receiving statin had a better overall survival compared to patients who does not receive statin (HR 0.71, 95% CI 0.51-0.97, p = 0.03, I2 = 76%). However, there was insignificant difference in terms of CSS, DFS, and PFS between RCC patients receiving statin and without statin. Conclusions: Statin has substantial benefits for improving OS. Even though the outcomes for CSS, DFS, and PFS were insignificant, the potential role of statins as a supplementary therapy in surgically treated RCC still requires further investigation.


Bray F, Ferlay J, Soerjomataram I, Siegel RL, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68:394-424. DOI: https://doi.org/10.3322/caac.21492

Hanna N, Sun M, Meyer CP, et al. Survival Analyses of Patients With Metastatic Renal Cancer Treated With Targeted Therapy With or Without Cytoreductive Nephrectomy: A National Cancer Data Base Study. J Clin Oncol. 2016; 34:3267-75. DOI: https://doi.org/10.1200/JCO.2016.66.7931

Krabbe LM, Bagrodia A, Margulis V, Wood CG. Surgical Management of Renal Cell Carcinoma. Semin Intervent Radiol 2014; 31:27. DOI: https://doi.org/10.1055/s-0033-1363840

Teloken PE, Thompson RH, Tickoo SK, et al. Prognostic Impact of Histological Subtype on Surgically Treated Localized Renal Cell Carcinoma. J Urol 2009; 182:2132-6. DOI: https://doi.org/10.1016/j.juro.2009.07.019

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. 2020; 38:1525-33. DOI: https://doi.org/10.1007/s00345-019-02930-4

Brierley J, Gospodarowicz MD, Wittekind CT. TNM Classification of Malignant Tumors International Union Against Cancer. 8th. Oxford, England: Wiley; 2017. Wiley 2017

Larkin JMG, Eisen T. Kinase inhibitors in the treatment of renal cell carcinoma. Crit Rev Oncol Hematol 2006; 60:216-26. DOI: https://doi.org/10.1016/j.critrevonc.2006.06.008

Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011; 378:1931-9. DOI: https://doi.org/10.1016/S0140-6736(11)61613-9

Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized

phase III trial. J Clin Oncol 2010; 28:1061-8. DOI: https://doi.org/10.1016/S1040-1741(10)79503-8

Li X, Shong K, Kim W, et al. Prediction of drug candidates for clear cell renal cell carcinoma using a systems biology-based drug repositioning approach. EBioMedicine 2022; 78:1039633. DOI: https://doi.org/10.1016/j.ebiom.2022.103963

Neumann E, Klaiber P, Freitag K, et al. Assessment of concomitant non-oncologic medication in patients with surgically treated renal cell carcinoma: impact on prognosis, cell-cycle progression and proliferation. J Cancer Res Clin Oncol 2019; 145:1835-43. DOI: https://doi.org/10.1007/s00432-019-02914-2

Santoni M, Monteiro FSM, Massari F, et al. Statins and renal cell carcinoma: Antitumor activity and influence on cancer risk and survival. Crit Rev Oncol Hematol. 2022; 176:103731. DOI: https://doi.org/10.1016/j.critrevonc.2022.103731

Seckl MJ, Ottensmeier CH, Cullen M, et al. Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Small-Cell Lung Cancer (LUNGSTAR). J Clin Oncol. 2017; 35:1506-14. DOI: https://doi.org/10.1200/JCO.2016.69.7391

Kawata S, Yamasaki E, Nagase T, et al. Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial. Br J Cancer 2001; 84:886-91. DOI: https://doi.org/10.1054/bjoc.2000.1716

Alarfi H, Youssef LA, Salamoon M. A Prospective, Randomized, Placebo-Controlled Study of a Combination of Simvastatin and Chemotherapy in Metastatic Breast Cancer. J Oncol. 2020; 2020:4174395. DOI: https://doi.org/10.21203/rs.2.16886/v2

Nayan M, Finelli A, Jewett MAS, et al. Statin use and kidney cancer outcomes: A propensity score analysis. Urol Oncol. 2016; 34:487.e1-487.e6. DOI: https://doi.org/10.1016/j.urolonc.2016.06.007

Viers BR, Houston Thompson R, Psutka SP, et al. The association of statin therapy with clinicopathologic outcomes and survival

among patients with localized renal cell carcinoma undergoing nephrectomy. Urol Oncol. 2015; 33:388.e11-8. DOI: https://doi.org/10.1016/j.urolonc.2015.01.009

Kaffenberger SD, Lin-Tsai O, Stratton KL, et al. Statin use is associated with improved survival in patients undergoing surgery for renal cell carcinoma. Urol Oncol. 2015; 33:21.e11-21.e17. DOI: https://doi.org/10.1016/j.urolonc.2014.10.007

Hamilton RJ, Morilla D, Cabrera F, et al. The association between statin medication and progression after surgery for localized renal cell carcinoma. J Urol 2014; 191:914-9. DOI: https://doi.org/10.1016/j.juro.2013.10.141

Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions®.

Haddad AQ, Jiang L, Cadeddu JA, et al. Statin Use and Serum Lipid Levels Are Associated With Survival Outcomes After Surgery for Renal Cell Carcinoma. Urology. 2015; 86:1146-52. DOI: https://doi.org/10.1016/j.urology.2015.09.015

Nayan M, Punjani N, Juurlink DN, et al. Statin use and kidney cancer survival outcomes: A systematic review and meta-analysis. Cancer Treat Rev 2017; 52:105-16. DOI: https://doi.org/10.1016/j.ctrv.2016.11.009

Luo Y, She DL, Xiong H, et al. The Prognostic Effect of Statin Use on Urologic Cancers: An Updated Meta-Analysis of 35 Observational Studies. Medicine (Baltimore). 2015; 94:e1523. DOI: https://doi.org/10.1097/MD.0000000000001523

Wu P, Xiang T, Wang J, et al. Statin use and the overall survival of renal cell carcinoma: A meta-analysis. Clin Invest Med. 2020; 43:E17-23. DOI: https://doi.org/10.25011/cim.v43i4.34908

McKay RR, Lin X, Albiges L, et al. Statins and survival outcomes in patients with metastatic renal cell carcinoma. Eur J Cancer. 2016; 52:155-62. DOI: https://doi.org/10.1016/j.ejca.2015.10.008

Nayan M, Hamilton RJ, Finelli A, et al. The value of complementing administrative data with abstracted information on smoking and obesity: A study in kidney cancer. Can Urol Assoc J 2017; 11:167-71. DOI: https://doi.org/10.5489/cuaj.4569

Di Bello E, Zwergel C, Mai A, Valente S. The Innovative Potential of Statins in Cancer: New Targets for New Therapies. Front Chem. 2020; 8:516. DOI: https://doi.org/10.3389/fchem.2020.00516

Petyaev IM. Improvement of hepatic bioavailability as a new step for the future of statin. Arch Med Sci. 2015; 11:406-10.

Petyaev IM. Improvement of hepatic bioavailability as a new step for the future of statin. Arch Med Sci 2015; 11:406. DOI: https://doi.org/10.5114/aoms.2015.50972

Stepanovska Tanturovska B, Manaila R, Fabbro D, Huwiler A. Lipids as Targets for Renal Cell Carcinoma Therapy. Int J Mol Sci. 2023; 24:3272. DOI: https://doi.org/10.3390/ijms24043272

Calderon RM, Cubeddu LX, Goldberg RB, Schiff ER. Statins in the Treatment of Dyslipidemia in the Presence of Elevated Liver Aminotransferase Levels: A Therapeutic Dilemma. Mayo Clin Proc 2010; 85:349. DOI: https://doi.org/10.4065/mcp.2009.0365

Adli, G., Yogiswara, N., Gde Tirta Yoga Yatindra, I. B., Putra, R. M., & Djatisoesanto, W. (2023). Impact of statin on renal cell carcinoma patients undergoing nephrectomy. Does it affect cancer progression and improves survival? A Systematic Review and Meta-Analysis. Archivio Italiano Di Urologia E Andrologia, 95(3). https://doi.org/10.4081/aiua.2023.11672

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