Prognostic Impact of Metastatic Pattern in Renal Cell Carcinoma: IMDC, IMDC-7, and Meet-URO Scores

Main Article Content

Okan Cetin
Nihan Eren
Melin Aydan Ahmed
Meltem Ekenel
Mert Basaran

Keywords

Metastatic renal cell carcinoma, Prognosis, Risk score , IMDC, IMDC-7 , Meet-URO

Abstract

The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score is widely used for prognostic stratification in metastatic renal cell carcinoma (mRCC); however, the value of extended models incorporating metastatic site information remains uncertain in patients treated with first-line tyrosine kinase inhibitor (TKI) monotherapy. We retrospectively analyzed 183 patients with mRCC who received first-line TKI therapy (sunitinib, pazopanib, or cabozantinib) between 2013 and 2023. The overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier analysis and Cox regression models, and the prognostic performance of IMDC, IMDC-7, and Meet-URO scores was compared using Harrell’s concordance index. At baseline, 47% of patients had metastases to high-risk sites (bone, liver, or brain), and 36% had three or more metastatic sites. In univariate analyses, bone, liver, and brain metastases as well as the presence of ≥3 metastatic sites were associated with significantly shorter OS and PFS. On multivariable analysis, anemia, poor performance status, absence of prior nephrectomy, and ≥3 metastatic sites independently predicted worse OS, while anemia, poor performance status, and bone metastasis remained independently associated with inferior PFS. All three prognostic models effectively stratified survival outcomes; however, IMDC-7 demonstrated the highest discriminatory ability for OS, followed by IMDC and Meet-URO. These findings highlight the strong prognostic impact of both metastatic burden and distribution in mRCC and support the incorporation of metastatic site assessment into routine risk stratification, particularly in settings where access to immune-based combination therapies remains limited.

Abstract 3 | PDF Downloads 2 XML Downloads 1 HTML Downloads 0

References

1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63. https://doi.org/0.3322/caac.21834
2. Kang M, Choi J, Kim J, Sung HH, Jeon HG, Jeong BC, et al. Prognostic impact of bone metastasis on survival outcomes in patients with metastatic renal cell carcinoma treated by first line tyrosine kinase inhibitors: A propensity-score matching analysis. J Cancer. 2020;11(24):7202–8. https://doi.org/10.7150/jca.48062
3. Shuch B, La Rochelle JC, Klatte T, Riggs SB, Liu W, Kabbinavar FF, et al. Brain metastasis from renal cell carcinoma: Presentation, recurrence, and survival. Cancer. 2008;113(7):1641–8. https://doi.org/10.1002/cncr.23769
4. McKay RR, Kroeger N, Xie W, Lee JJ, Knox JJ, Bjarnason GA, et al. Impact of bone and liver metastases on patients with renal cell carcinoma treated with targeted therapy. Eur Urol. 2014;65(3):577–84. https://doi.org/10.1016/j.eururo.2013.08.012
5. Zhang GM, Zhu Y, Gu WJ, Zhang HL, Shi GH, Ye DW. Pretreatment neutrophil-to-lymphocyte ratio predicts prognosis in patients with metastatic renal cell carcinoma receiving targeted therapy. Int J Clin Oncol. 2016;21(2):373–8. https://doi.org/10.1007/s10147-015-0894-4
6. Yücel KB, Yekedüz E, Karakaya S, Tural D, Ertürk I, Erol C, et al. The relationship between systemic immune inflammation index and survival in patients with metastatic renal cell carcinomatreated withtyrosine kinase inhibitors. Sci Rep. 2022;12(1):16559. https://doi.org/10.1038/s41598-022-20056-3
7. Rebuzzi SE, Signori A, Banna GL, Maruzzo M, De Giorgi U, Pedrazzoli P, et al. Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: The development of a novel prognostic score (Meet-URO 15 study). Ther Adv , Med Oncol. 2021;13:17588359211019642. https://doi.org/10.1177/17588359211019642
8. Rebuzzi SE, Signori A, Buti S, Banna GL, Murianni V, Damassi A, et al. Validation of the Meet-URO score in patients with metastatic renal cell carcinoma receiving first-line nivolumab and ipilimumab in the Italian Expanded Access Program. ESMO Open. 2022;7(6):100634. https://doi.org/10.1016/j.esmoop.2022.100634
9. Rebuzzi SE, Cerbone L, Signori A, Santoni M, Murianni V, De Giorgi U, et al. Application of the Meet-URO score to metastatic renal cell carcinoma patients treated with second- and third-line cabozantinib. Ther Adv Med Oncol. 2022;14:17588359221079580. https://doi.org/10.1177/17588359221079580
10. He S, Liu H, Chen J, Zeng H. Validation of the Meet-URO score in metastatic clear cell renal cell carcinoma patients receiving second or third-line tyrosine kinase inhibitors-immune checkpoint inhibitors combination therapy. J Transl Med. 2024;22(1):232. https://doi.org/10.1186/s12967-024-05014-z
11. Di Nunno V, Mollica V, Schiavina R, Nobili E, Fiorentino M, Brunocilla E, et al. Improving IMDC prognostic prediction through evaluation of initial site of metastasis in patients with metastatic renal cell carcinoma. Clin Genitourin Cancer. 2020;18(2):e83–e90. https://doi.org/10.1016/j.clgc.2019.08.007
12. Massari F, Di Nunno V, Guida A, Costa Silva CA, Derosa L, Mollica V, et al. Addition of primary metastatic site on bone, brain, and liver to IMDC criteria in patients with metastatic renal cell carcinoma: A validation study. Clin Genitourin Cancer. 2021;19(1):32–40. https://doi.org/10.1016/j.clgc.2020.06.003
13. Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, et al. Nivolumab plus Cabozantinib versus Sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384(9):829–41. https://doi.org/10.1056/NEJMoa2026982
14. Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, et al. Pembrolizumab plus Axitinib versus Sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1116–27. https://doi.org/10.1056/NEJMoa1816714
15. Heng DY, Xie W, Regan MM, Harshman LC, Bjarnason GA, Vaishampayan UN, et al. External validation and comparison with other models of the International Metastatic RCC Database Consortium prognostic model: A population-based study. Lancet Oncol. 2013;14(2):141–8. https://doi.org/10.1016/S1470-2045(12)70559-4
16. Tanaka N, Mizuno R, Ito K, Shirotake S, Yasumizu Y, Masunaga A, et al. External validation of the MSKCC and IMDC risk models in patients treated with targeted therapy as first-line and subsequent second-line treatment: A Japanese multi-institutional study. Eur Urol Focus. 2016;2(3):303–9. https://doi.org/10.1016/j.euf.2015.11.001
17. Mantia CM, Jegede OA, McDermott DF, Heng DYC, Xie W, Choueiri TK, et al. Long-term performance of prognostic models for advanced renal cell carcinoma in the era of improved survival with immune checkpoint inhibitors. JCO Oncol Pract. 2026;22(5):804–12. https://doi.org/10.1200/OP-25-00089
18. Wei H, Miao J, Cui J, Zheng W, Chen X, Zhang Q, et al. The prognosis and clinicopathological features of different distant metastases patterns in renal cell carcinoma: Analysis based on the SEER database. Sci Rep. 2021;11(1):17822. https://doi.org/10.1038/s41598-021-97365-6
19. Rose TL, Kim WY. Renal cell carcinoma: A review. JAMA. 2024;332(12):1001–10. https://doi.org/10.1001/jama.2024.12848
20. Escudier B, Powles T, Motzer RJ, Olencki T, Frontera OA, Oudard S, et al. Cabozantinib, a new standard of care for patients with advanced renal cell carcinoma and bone metastases? Subgroup analysis of the METEOR Trial. J Clin Oncol. 2018;36(8):765–72. https://doi.org/10.1200/jco.2017.74.7352
21. Beuselinck B, Oudard S, Rixe O, Wolter P, Blesius A, Ayllon J, et al. Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib. Ann Oncol. 2011;22(4):794–800. https://doi.org/10.1093/annonc/mdq554
22. Damassi A, Cremante M, Signori A, Rebuzzi SE, Fornarini G, Giudice GC, et al. Prognostic stratification by the Meet-URO score in real-world older patients with metastatic renal cell carcinoma (mRCC) receiving cabozantinib: A subanalysis of the prospective ZEBRA study (Meet-URO 9). Clin Genitourin Cancer. 2024;22(2):126–133.e2. https://doi.org/10.1016/j.clgc.2023.10.001
23. Rebuzzi SE, Fornarini G, Signori A, Buti S, Procopio G, De Giorgi U, et al. International multicenter real-world REGistry for patients with metastatic renAL cell carcinoma—Meet-URO 33 study (REGAL study). BMC Cancer. 2024;24(1):757. https://doi.org/10.1186/s12885-024-12319-1