GU Cancers 2026 | CYTOSHRINK: SBRT with ipilimumab and nivolumab in treatment-naïve mRCC
Aly-Khan Lalani, MD, McMaster University, Hamilton, Canada, discusses the CYTOSHRINK trial (NCT04090710), the first randomized study evaluating stereotactic body radiation therapy (SBRT) with ipilimumab and nivolumab versus immunotherapy alone in previously untreated metastatic renal cell carcinoma (RCC). While twelve-month progression-free survival was not improved compared to immunotherapy alone, the addition of cytoreductive SBRT was considered safe with no new safety signals, warranting further follow-up of overall survival and quality of life outcomes. This interview took place at the 2026 ASCO GU Cancers Symposium in San Francisco, CA.
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Transcript
The cytosine trial was designed back in 2019 in an era where we had come out of data from CARMENA and SURTIME, which challenged the use of routine upfront cytoreductive nephrectomy in most IMDC intermediate and poor-risk patients. So at the time, we designed a randomized phase two clinical trial evaluating the addition of stereotactic body radiation therapy, or SBRT, early as an upfront cytoreductive approach versus patients getting the standard of care immunotherapy...
The cytosine trial was designed back in 2019 in an era where we had come out of data from CARMENA and SURTIME, which challenged the use of routine upfront cytoreductive nephrectomy in most IMDC intermediate and poor-risk patients. So at the time, we designed a randomized phase two clinical trial evaluating the addition of stereotactic body radiation therapy, or SBRT, early as an upfront cytoreductive approach versus patients getting the standard of care immunotherapy. Yeah, so what we found is that, you know, at the era this trial was conducted, there were, I would say, a very high-risk population in the sense of the size of the primary renal mass, good balance between IMDC intermediate and poor-risk patients, and all the other standard features of a first-line trial. But there were more patients presenting with liver metastasis in the interventional arm, bony metastasis. And so that’s certainly in a small randomized phase two, can impact outcomes. Ultimately, we did not see the one-year PFS rate of adding SBRT to nivolumab plus ipilimumab versus nivolumab and ipilimumab improved. But we did see some interesting findings by the IMDC risk groups. And most importantly, in those who responded in both arms, the ongoing responses were better in patients who got the SBRT intervention, which tells you something about the biology that we need to uncover. In terms of radiation administered, there was no really detriment to giving SBRT in patients getting nivolumab and ipilimumab or vice versa. So the safety and delivery of both modalities was reasonable. And we kept a close eye, obviously, on kidney injury and other type of renal toxicity. But consistent with what we know about SBRT, there’s actually very good renal preservation and a safe way to deliver radiation to patients to preserve renal function. So all in all, I think we’re going to have more follow-up of overall survival, quality of life. We have patients who had treatment beyond progression in the intervention arm. We had patients who got downstream nephrectomies in the intervention arm. And we have biomarkers. We’re looking at tissue, serial blood collections, and serial gut microbiome collections.
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