Defining the Optimal Window for Cytoreductive SABR in Metastatic Kidney Cancer

In an interview with CancerNetwork®, at the 2026 European Society for Medical Oncology (ESMO) Congress,Shankar Siva, MBBS, PhD, FRANZCR, a professor and radiation oncologist who leads the stereotactic ablative body radiotherapy (SABR) program at the Peter MacCallum Cancer Centre in Melbourne, Australia, explained how clinicians may time local therapy to the primary tumor in patients with metastatic renal cell carcinoma (RCC) receiving immune checkpoint inhibitor (ICI)– or tyrosine kinase inhibitor (TKI)–based combinations.

Siva noted that emerging biomarkers, including circulating tumor DNA and functional PET imaging, may eventually help guide these decisions, but that timing remains clinically driven. He pointed to long-term data from the phase 3 CheckMate 214 trial (NCT02231749), in which nivolumab (Opdivo) plus ipilimumab (Yervoy) continued to improve overall survival vs sunitinib (Sutent) in the intent-to-treat population at a median follow-up of 8 years (HR, 0.72; 95% CI, 0.62-0.83), as support for considering intervention around 12 months into a response.¹

He also highlighted 2 ongoing randomized trials evaluating earlier local therapy in the ICI era. The phase 3 PROBE/SWOG S1931 trial (NCT04510597) randomly assigns patients after 10 to 14 weeks of ICI-based combination therapy to cytoreductive nephrectomy followed by systemic therapy or continued systemic therapy alone, with overall survival as the primary end point.² The phase 2 SAMURAI/NRG-GU012 trial (NCT05327686) is evaluating SABR to the primary tumor plus immunotherapy vs immunotherapy alone in patients who are not recommended for or decline nephrectomy, with nephrectomy and radiographic progression-free survival as the primary end point.³

Transcript:

CancerNetwork: How do you define the optimal window and biomarker criteria for determining whether a patient with primary metastatic kidney cancer should undergo cytoreductive SABR vs continuing with an immune checkpoint inhibitor doublet or TKI-based combination?

Siva: Response-based adaptive treatment in kidney cancer is an evolving space, whether we are talking about stereotactic radiation delivered to the primary or metastatic sites or about alternative local therapies like surgery. Both were discussed in the educational session today at ESMO. The idea of response-based adaptation is either escalation or de-escalation of treatment, and that can include the systemic therapy or the local therapies.

We discussed the opportunity of using novel biomarkers, such as circulating tumor DNA [ctDNA] in the blood, or imaging biomarkers, specifically functional imaging with fluorodeoxyglucose [FDG] PET, prostate-specific membrane antigen [PSMA] PET, and carbonic anhydrase IX [CAIX] PET scans, as a window to assess when to adapt treatment strategies. At the moment, however, it is still clinically driven.

When we think about using radiation or surgery to the primary kidney in a patient who is responding to systemic therapy, we typically consider it around the 12-month time point. There is some variability around this, and it can be as long as 2 years. However, data from the [phase 3 CheckMate 214 trial] indicate that most patients who are responding will plateau at around 12 to 24 months. Rather than intervening up front, the intervention could come at the 12-month time point.

There are, of course, ongoing randomized trials, such as [the phase 3 PROBE/SWOG S1931 trial] and the [phase 2 SAMURAI/NRG-GU012 trial], which are investigating nephrectomy and SABR, respectively. But they are doing it up front, so we will soon find out whether early intervention is better or whether it should be delayed to 12 months after initial response to systemic therapy.

References

1. Tannir NM, Albigès L, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 8-year follow-up results of efficacy and safety from the phase III CheckMate 214 trial. Ann Oncol. 2024;35(11):1026-1038. doi:10.1016/j.annonc.2024.07.727
2. Vaishampayan UN, Tangen C, Tripathi A, et al. SWOG S1931 (PROBE): phase III randomized trial of immune checkpoint inhibitor (ICI) combination regimen with or without cytoreductive nephrectomy (CN) in advanced renal cancer. J Clin Oncol. 2022;40(suppl 6):TPS402 doi:10.1200/JCO.2022.40.6_suppl.TPS402
3. Hall WA, Karrison T, McGregor BA, et al. NRG-GU012: randomized phase II stereotactic ablative radiation therapy (SABR) for metastatic unresected renal cell carcinoma (RCC) receiving immunotherapy (SAMURAI). J Clin Oncol. 2024;42(suppl 16):TPS4613. doi:10.1093/oncolo/oyad216.020