Adrenal Metastases as Sanctuary Sites in Advanced Renal Cancer

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Ulka Vaishampayan, MD
Harsh Shah
Mohammad F Asad
Dongping Shi
Brenda Dickow
Stacey Suisham
Jason Domina
Michael L. Cher
Julie Samantray
Hussein D. Aoun


kidney cancer, immunotherapy, clear cell, metastases


Involvement of adrenal gland in kidney cancer represents a unique site of metastasis with a distinct clinical course. The cases are typically resistant to immune therapy and need local therapy management. A case series of patients with adrenal metastases was reviewed to highlight the nuances of clinical course and therapy. We reviewed renal cancer carcinoma (RCC) cases with adrenal metastases at Karmanos Cancer Center, Detroit MI. Medical records were reviewed to collect relevant case information. Next-generation sequencing, tumor mutation burden testing, and programmed death ligand bio-markers were evaluated in five cases. Twelve cases were reviewed; all were males with a median age of 49.5 years. Three patients presented with adrenal metastases only and were treated with local therapy. Three received interleukin-2 (IL-2). One patient relapsed with bilateral adrenal lesions after 11 years of remission, post-IL-2 therapy. Five cases received immune checkpoint inhibitor (ICI) and one received antivascular therapy. ICI therapy was followed by ablation of residual adrenal metastases in three patients. Genomic profiling was available in five cases. All were BAP1 and PD-L1 negative.Patho-genic mutations in PBRM1, SETD2, and VHL were noted. All patients with residual adrenal metastases responded to antivascular therapies or to local ablation. One patient died 17 years after diagnosis and 11 patients are alive at a median follow-up of 9.5 years. Adrenal metastases in RCC have a distinct clinical course. They can represent a sanctuary site of relapse/residual disease following treatment with immune therapy. Management with local therapy can induce durable remissions. Systemic management with antivascular therapies also demonstrated favorable responses. Further investigation should focus on the unique clinical course and optimal management of adrenal metastases in kidney cancer.

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1. Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, SahiC, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endo-thelial growth factor-targeted agents: Results from a large, multicenter study. J Clin Oncol. 2009;27(34):5794–9. http://dx.doi. org/10.1200/JCO.2008.21.4809
2. Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001;345(23):1655–9. http://dx.doi. org/10.1056/NEJMoa003013
3. Espinoza E, Hassani A, Vaishampayan U, Shi D, Pontes JE, Weaver DW. Surgical excision of duodenal/pancreatic metastatic renal cell carcinoma. Front Oncol. 2014;4:218. http://dx.doi. org/10.3389/fonc.2014.00218
4. Zurimendi GG, Ibarguren LR, Castaños LD, Pereda RF, Olabarrieta AU, De Casasola-Rodríguez GG, et al. Pancreatic metastasis of primary kidney cancer: A presentation of a series of clinical cases and revision of the literature. Arch Esp Urol. 2020;73(2):147–54.
5. McKay RR, Lin X, Perkins JJ, Heng DY, Simantrov R, Choueiri TK. Prognostic significance of bone metastases and bisphosphonate therapy in patients with renal cell carcinoma. Eur Urol. 2014;66(3):502–9.
6. Gulati S, Vaishampayan U. Current state of systemic therapies for advanced renal cell carcinoma. Curr Oncol Rep. 2020;22:26.
7. Graham J, Heng DYC, Brugarolas J, Vaishampayan U. Personalized management of advanced kidney cancer. Am Soc Clin Oncol Educ Book. 2018;38:330–41. http://dx.doi. org/10.1200/EDBK_201215
8. Hammers HJ, Vonmerveldt D, Ahn C, Nadal RM, Drake CG, Folkert MR, et al. Combination of dual immune checkpoint inhibition (ICI) with stereotactic radiation (SBRT) in metastatic renal cell carcinoma (mRCC) (RADVAX RCC). J Clin Oncol. 2020;38(Suppl 6):Abstr 614. JCO.2020.38.6_suppl.614
9. Masini C, Iotti C, De Giorgi U, Bellia RS, Buti S, Salaroli F, et al. Nivolumab (NIVO) in combination with stereotactic body radiotherapy (SBRT) in pretreated patients (pts) with metastatic renal cell carcinoma (mRCC): First results of phase II NIVES study. J Clin Oncol. 2020;38:(Suppl 6): Abstr 613. http://dx.doi. org/10.1200/JCO.2020.38.6_suppl.613
10. Spartalis E, Drikos I, Ioannidis A, Chrysikos D, Athanasiadis DI, Spartalis M, et al. Metastatic carcinomas of the adrenal glands: From diagnosis to treatment. Anticancer Res. 2019;39(6):2699–710. anticanres.13395
11. Welch BT, Callstrom MR, Carpenter PC, WassCT, Welch TL, BoorjianSA, et al. A single-institution experience in image-guided thermal ablation of adrenal gland metastases. J VascInterv Radiol. 2014;25(4):593–8. http://dx.doi. org/10.1016/j.jvir.2013.12.013
12. Scorsetti M, Alongi F, Filippi AR, Pentimalli S, Navarria P, ClericiE, et al. Long-term local control achieved after hypofractionated stereotactic body radiotherapy for adrenal gland metastases: A retrospective analysis of 34 patients. Acta Oncol. 2012;51(5):618–23. 86X.2011.652738
13. Bang HJ, Littrup PJ, Goodrich DJ, Currier BP, Aoun HD, Heilbrun LK, et al. Percutaneous cryoablation of metastatic renal cell carcinoma for local tumor control: Feasibility, outcomes, and estimated cost-effectiveness for palliation. J VascInterv Radiol. 2012;23(6):770–7. jvir.2012.03.002
14. Huang ZM, Li HZ, Xiao H, Ji ZG. Melanoma adrenal metastasis: Report of 3 cases and literature review. Zhonghua Yi Xue Za Zhi. 2010;90(16):1123–5.
15. Nguyen MC, Shah MH, Liebner DA, Backes FJ, Phay J, Shirley LA. The adrenal gland as a sanctuary site of metastases after pembrolizumabtreatment: A case series. J Natl Compr. Canc Netw. 2018;16(11):1279–83. jnccn.2018.7059
16. Tan MH, IyengarR, Mizokami-Stout K, YentzS, MacEachernMP, Shen LY, et al. Spectrum of immune check-point inhibitors induced endocrinopathies in cancer patients: A scoping review of case reports. Clin Diabetes Endocrinol. 2019;5:117.
17. Miao D, Margolis CA, Gao W, Voss MH, Li W, Martini DJ, et al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science. 2018 Feb 16;359(6377):801–6.
18. Clark DJ, Dhanasekaran SM, Petralia F, Pan J, Song X, Hu Y, et al. Integrated proteogenomic characterization of clear cell renal cell carcinoma. Cell. 2019;179:964–83. http://dx.doi. org/10.1016/j.cell.2019.10.007
19. Byeon KY, Ha YS, Choi SH, Kim BS, Kim HT, YooES, et al. Predictive factors for adrenal metastasis in extra-adrenal malignancy patients with solitary adrenal mass. J SurgOncol. 2018;118:1271–6.
20. Uryvaev A, Passhak M, Hershkovits D, Sabo E, Bar-Sela G. The role of tumor-infiltrating lymphocytes (TILs) as a predictive biomarker of response to anti-PD1 therapy in patients with metastatic non-small cell lung cancer or metastatic mela-noma. Med Oncol. 2018;35(3):25. s12032-018-1080-0