Evolving Patterns of Metastasis in Renal Cell Carcinoma: Do We Need to Perform Routine Bone Imaging?
Main Article Content
Keywords
Bone Imaging, Immune Checkpoint Inhibitors, Metastatic Distribution, Renal Cell Carcinoma, Tyrosine Kinase Inhibitors
Abstract
Advance diagnostic and treatment modalities have improved outcomes for renal cell carcinoma (RCC) patients, but the prognosis for those with metastatic disease (mRCC) remains poor. As given metastatic distribution is critical in guiding treatment decisions for mRCC patients, we evaluated evolving metastatic patterns to assess if our current practice standards effectively address patient needs. A systematic literature review was performed to identify all publicly available prospective clinical trials in metastatic renal cell carcinoma (mRCC) from 1990 to 2018. A total of 16,899 mRCC patients from 127 qualified phase I–III clinical trials with metastatic site documentations were included for analysis for incidence of metastases to lung, liver, bone, and lymph nodes (LNs) over time. Studies were categorized into three treatment eras based on the timing of regulatory approval: Cytokine Era (1990-2004), vascular endothelial growth factor/tyrosine kinase inhibitor (TKI) Era (2005-2016), and immune checkpoint inhibitor/TKI Era (ICI-TKI, 2017-2018) and also classified as first-line only (FLO) or second-line and beyond (SLB). Overall, an increase in the incidence of bone and LNs metastases in FLO and SLB, and lung metastases in FLO, was seen over the three treatment eras. Generally, the burden of disease is higher in SLB when compared with FLO. Importantly, in the ICI-TKI era, the incidences of bone metastasis are 28% in FLO and 29% in SLB settings. The disease burden in patients with mRCC has increased steadily over the past three decades. Given the unexpectedly high rate of bone metastasis, routine dedicated bone imaging should be considered in all patients with mRCC.
References
2. Bianchi M, Sun M, Jeldres C, Shariat SF, Trinh QD, Briganti A, et al. Distribution of metastatic sites in renal cell carcinoma: A population-based analysis. Ann Oncol Off J Eur Soc Med Oncol. 2012;23(4):973–80. http://dx.doi.org/10.1093/annonc/mdr362
3. Meyer CP, Sun M, Karam JA, Leow JJ, de Velasco G, Pal SK, et al. Complications after metastasectomy for renal cell carcinoma- A population-based assessment. Eur Urol. 2017;72(2):171–4. http://dx.doi.org/10.1016/j.eururo.2017.03.005
4. Griffin N, Gore ME, Sohaib SA. Imaging in metastatic renal cell carcinoma. AJR Am J Roentgenol. 2007;189(2):360–70. http://dx.doi.org/10.2214/AJR.07.2077
5. Patard JJ. Incidental renal tumours. Curr Opin Urol. 2009;19(5):454–8. http://dx.doi.org/10.1097/MOU.0b013e32832f0ccd
6. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47. http://dx.doi.org/10.1016/j.ejca.2008.10.026
7. Motzer RJ, Jonasch E, Michaelson MD, Nandagopal L, Gore JL, George S, et al. NCCN guidelines insights: Kidney cancer, Version 2.2020. J Natl Compr Canc Netw. 2019;17(11):1278–85. http://dx.doi.org/10.6004/jnccn.2019.0054
8. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2):125–34. http://dx.doi.org/10.1056/NEJMoa060655
9. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115–24. http://dx.doi.org/10.1056/NEJMoa065044
10. Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369(8):722–31. http://dx.doi.org/10.1056/NEJMoa1303989
11. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): A randomised phase 3 trial. Lancet (London, England). 2011;378(9807):1931–9. http://dx.doi.org/10.1016/S0140-6736(11)61613-9
12. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–13. http://dx.doi.org/10.1056/NEJMoa1510665
13. 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. http://dx.doi.org/10.1056/NEJMoa1816714
14. Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1103–15. http://dx.doi.org/10.1056/NEJMoa1816047
15. Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–90. http://dx.doi.org/10.1056/NEJMoa1712126
16. Choueiri TK, Halabi S, Sanford BL, Hahn O, Michaelson MD, Walsh MK, et al. Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: The alliance A031203 CABOSUN trial. J Clin Oncol Off J Am Soc Clin Oncol. 2017;35(6):591–7. http://dx.doi.org/10.1200/JCO.2016.70.7398
17. Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1814–23. http://dx.doi.org/10.1056/NEJMoa1510016
18. Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015;16(15):1473–82. http://dx.doi.org/10.1016/S1470-2045(15)00290-9
19. Heng DYC, Choueiri TK, Rini BI, Lee J, Yuasa T, Pal SK, et al. Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials. Ann Oncol Off J Eur Soc Med Oncol. 2014;25(1):149–54. http://dx.doi.org/10.1093/annonc/mdt492
20. McKay RR, Lin X, Perkins JJ, Heng DYC, Simantov R, Choueiri TK. Prognostic significance of bone metastases and bisphosphonate therapy in patients with renal cell carcinoma. Eur Urol. 2014;66(3):502–9. http://dx.doi.org/10.1016/j.eururo.2014.02.040
21. Beuselinck B, Wolter P, Broom R. Re: Rana R. McKay, Xun Lin, Julia J. Perkins, Daniel Y.C. Heng, Ronit Simantov, Toni K. Choueiri. Prognostic significance of bone metastases and bisphosphonate therapy in patients with renal cell carcinoma. Eur Urol 2014;66:502–9. Eur Urol. 2014;66(3):e53–4. http://dx.doi.org/10.1016/j.eururo.2014.04.019
22. McKay RR, Kroeger N, Xie W, Lee JL, 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. http://dx.doi.org/10.1016/j.eururo.2013.08.012
23. Ruatta F, Derosa L, Escudier B, Colomba E, Guida A, Baciarello G, et al. Prognosis of renal cell carcinoma with bone metastases: Experience from a large cancer centre. Eur J Cancer. 2019;107:79–85. http://dx.doi.org/10.1016/j.ejca.2018.10.023
24. Blacher E, Johnson DE, Haynie TP. Value of routine radionuclide bone scans in renal cell carcinoma. Urology. 1985;26(5):432–4. http://dx.doi.org/10.1016/0090-4295(85)90148-7
25. Seaman E, Goluboff ET, Ross S, Sawczuk IS. Association of radionuclide bone scan and serum alkaline phosphatase in patients with metastatic renal cell carcinoma. Urology. 1996;48(5):692–5. http://dx.doi.org/10.1016/S0090-4295(96)00236-1
26. Chen SC, Kuo PL. Bone metastasis from renal cell carcinoma. Int J Mol Sci. 2016;17(6):987. http://dx.doi.org/10.3390/ijms17060987
27. Eustace S, Tello R, DeCarvalho V, Carey J, Wroblicka JT, Melhem ER, et al. A comparison of whole-body turboSTIR MR imaging and planar 99mTc-methylene diphosphonate scintigraphy in the examination of patients with suspected skeletal metastases. AJR Am J Roentgenol. 1997;169(6):1655–61. http://dx.doi.org/10.2214/ajr.169.6.9393186
28. Chow E, Zeng L, Salvo N, Dennis K, Tsao M, Lutz S. Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol (R Coll Radiol). 2012;24(2):112–24. http://dx.doi.org/10.1016/j.clon.2011.11.004
29. Desautels DN, Harlos CH, Jerzak KJ. Role of bone-modifying agents in advanced cancer. Ann Palliat Med. 2020; 9 (3):1314–23. http://dx.doi.org/10.1016/j.clon.2011.11.004