met, and the median PFS was 4.1 months, which was not
improved from a prior study, CheckMate 025, in which
patients receiving nivolumab alone (without SBRT) experienced
a median PFS of 4.6 months.31 Given that approximately
half of the patients harbored 3 or more sites
of metastatic disease and that the dose of radiation (30
Gy in 3 fractions) was on the conservative side of that in
the aforementioned studies, improved clinical outcomes
may be observed in a study population with a more limited
volume of disease (3 sites) with a more aggressive
radiation regimen was utilized. The RADVAX trial evaluated
the combination nivolumab and ipilimumab with
SBRT at a higher dose (50 Gy in 5 fractions) than that
used in NIVES. The ORR of 56%, median PFS of 8.21
months, and the acceptable safety profile of the treatment
combination are promising.32 Further studies are
necessary to understand how to optimize immunotherapy
with SBRT to improve clinical outcomes.
In addition irradiation of metastatic sites, the utilization
of SBRT to the primary site of disease is growing.
Multiple studies have suggested high local control rates
(90-100%) with acceptable toxicity (grade 3 toxicity
<5%).33-36 The largest study published from the International
Radiosurgery Oncology Consortium for Kidney
(IROCK) included 223 patients who underwent SBRT to
the primary site only. 2- and 4y local control rates were
97.8%. A small decrease in kidney function was observed
with a mean decrease in GFR of 5.5 +/- 13.3
ml/min.36 A major limitation of these studies is the limited
follow-up time.
Conclusion
Treatment of oligometastatic RCC has evolved rapidly
and new treatment paradigms have emerged. In appropriately
selected patients, the use of SBRT has gained support
and has been integrated into widely accepted
guidelines for the treatment of oligometastases, such as
those by the National Comprehensive Cancer Network.
Nevertheless decisions need to be individualized to
achieve optimal local control based on consideration of
IMDC risk factors and an approach reflecting multimodal
treatments. Careful patient selection for surgical
metastasectomy is essential. Patients with a good indication
for surgical metastasectomy include those with solitary
or oligometastatic lesions, symptomatic metastases
deteriorating quality of life, resistance to radiotherapy
and/or systemic therapies, and easy surgical accessibility
and resectability with a lower rate of complications.
There is growing evidence supporting the use of active
surveillance in a well-selected subset of patients with indolent,
asymptomatic, and good-risk mRCC, thus mitigating
the need in some cases for immediate aggressive
treatment.
References
1. Palma DA, Louie AV, Rodrigues B. New strategies in stereotactic radiotherapy
for oligometastases. Clin Can Res. 20155;21:5198-5204.
2. Huang F, Wu G, Yang K. Oligometastasis and oligo-recurrence: more than
a mirage. Radiat Oncol. 2014;9:230.
3. Weichselbaum RR, Hellman. Oligometastasis revisited. Nat reviews
Clinical Oncology. 2011;8:3788-382.
4. Turajlic, Xu, Litchfield et al: Tracking Cancer Evolution Reveals Constrained
Routes to Metastases: TRACERx Renal. Cell, 173:581-594, 2018.
5. La Rochelle J, Klatte T, Dastane A, Rao PN, Seligson D, Said J, Shuch
48 Kidney Cancer Journal
B, Zomorodian N, Kabbinavar F, Belldegrun A, Pantuck AJ: Chromosome
9p deletions identify an aggressive phenotype of localized clear
cell renal cell carcinoma: implications for pre-operative biopsy and active
surveillance of small renal tumors. Cancer, 116:4696-702, 2010.
6. Kroeger N, Klatte T, Chamie K, Rao PN, Birkhäuser FD, Sonn GA, Riss
J, Kabbinavar FF, Belldegrun AS, Pantuck AJ. Deletions of chromosomes
3p and 14q molecularly subclassify clear cell renal cell carcinoma. Cancer.
2013 Apr 15;119(8):1547-54
7. Zisman A, Pantuck AJ, Wieder J, et al. Risk group assessment and
clinical outcome algorithm to predict the natural history off patients
with surgically resected renal cell carcinoma. J Clin Oncol. 202;20:4559-
4566.
8. Pantuck A, Zisman A, Belldegrun AS. The changing natural history
of renal cell carcinoma. J Urol. 2001;166:1611-123.
9. Han K-R, Pantuck AJ, Bui MHT, et al. Number of metastatic sites
rather than location dictates overall survival of patients with node-negative
metastatic renal cell carcinoma. Urol. 61:314-319.
10. Lyon TD, Thompson RH, Shah PH, et al. Complete surgical metastatectomy
of renal cell carcinoma in the post-cytokine era. J Urol.
2020;203:275-282.
11. Kato S, Demura S, Murakami H, et al. Surgical metastasectomy for
renal cell carcinoma: which patients are the real candidates for surgery?
Ann Translational Med. 2019;(Suppl 8):S273.
12. Palumbo C, Pecoraro A, Knipper S, et al. Survival and complication
rates of metastasectomy in patients with metastatic renal cell carcinoma
treated exclusively with targeted therapy: a combined population
based analysis. Anticancer Res. 2019;39:357-4361.
13. Meyer CP, Sun M, Karam JA, et al. Complicati0ons after metastasectomy
for renal cell carcinoma—a population-based assessment. Eur
Urol. 2017;772:1771-174.
14. Beuselinck B, Oudard S, Rixe O, et al. Negative impact of bone
metastasis on outcome in clear-cell renal cell carcinoma treated with
sunitinib. Ann Oncol. 2011;22:794-800.
15. Leibovich BC, Cheville JC, Lohse CM et al. A scoring algorithm to
predict survival for patients with metastatic clear cell renal cell carcinoma:
a stratification tool for prospective clinical trials. J Urol. 2005;
174:1759-1763.
16. Yuasa T, Inoshita N, Saiura A, et al: Clinical Outcomes of patients
with pancreatic metastases from renal cell carcinoma. BMC Cancer,
15:46, 2015.
17. Ouzaid I, Capitanio U, Staehler M, et al. Surgical metastasectomy
in renal cell carcinoma: a systematic review. Eur Urol Oncol. 2019;2:141-
149.
18. Pierorazio PM, McKiernan JM, McCann TR, et al. Outcome after cytoreductive
nephrectomy for metastatic renal cell carcinoma is predicted
by fractional percentage of tumour volume removed. BJU Int.
2007;100:755-759.
19. Rini BI, Dorff TB, Elson P, et al. Active surveillance in metastatic
renal-cell carcinoma: a prospective, phase 2 trial. Lancet Oncol. 2016;
17:13177-1324.
20. Escudier B, Porta C, Schmidinger M, et al. Renal cell carcinoma:
ESMO Clinical Practice Guidelines for diagnosis, treatment and followup.
Ann Oncol. 2019;30:706-720.
21. Woldu SL, Matulay JT, Clinton TN, et al. Incidence and outcomes
of delayed targeted therapy after cytoreductive nephrectomy for
metastatic renal-cell carcinoma: a nationwide cancer registry study.
Clin Genitourin Cancer. 2018;1:1221-1235.
22. Bimbatti D, Ciccarese C, Fantinel E, et al. Predictive role of changes
in the tumor burden and International Metastatic Renal Cell Carinoma
Data Base Consortium class during active surveillance for metastatic
renal cell carcinoma. Urol. Oncol. 2018;3:526.
23. Ficarra V, Mosca A, Rossanese M, et al. Is active surveillance an option
for metachronous metastatic renal cell carcinoma. Ann Transl Med.
2019;7: 84.
24. Beckham TH, Imber BS, Simone CB. Stereotactic body radiation
therapy for oligometastatic renal cell carcinoma: improving outcomes
in an otherwise radioresistant malignancy. Ann Transl Med. 2019;
7(Suppl):S98.
25. Zaorsky NG, Lehrer E, Kothan G, et al. Stereotactic ablative radiation
therapy for oligometastatic renal cell carcinoma (SABR ORCA): a
meta-analysis of 28 studies. Eur Urol Oncol. 2019;2:515-523.
26. Dengina N, Mitin T, Gamayunov S, et al. Stereotactic body radiation
therapy in combination with systemic therapy for metastatic renal cell
carcinoma: a prospective multicenter study. ESMO Open. 2019;
4:e000535.
27. Hoerner-Riber, Duma M, Blanck O, et al. Stereotactic body radiotherapy
(SBRT) for pulmonary metastases from renal cell carcinoma—
a multicenter analysis of the German working group “Stereotactic
Radiotherapy.” Journal of Thoracic Disease. 2017;9:4512-4522.
(continued on page 62)