The Role of SBRT and Metastasis-Directed Therapy for RCC Treatment, Variant Histology Considerations

A roundtable discussion, moderated by Rana McKay, MD, discussed the latest updates in frontline treatment for renal cell carcinoma, including how data from the American Society of Clinical Oncology Genitourinary Cancers Symposium 2024 alters the treatment paradigm. Dr. McKay was joined by Nizar Tannir, MD; Hans Hammers, MD; and Katy Beckermann, MD.

In the second segment of the roundtable series, the panel considered the role of SBRT as well as metastasis-directed therapy in RCC. They also weighed in on various variant histology considerations.

Watch the next segment in this series.

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Dr. McKay: Dr. Hammers, you brought up metastasis-directed therapy and SBRT. How do you integrate that into your practice currently?

Dr. Hammers: Our institution, like MD Anderson, has done significant work with oligoprogressive disease. Dr. Tan, for instance, has contributed to this area. I believe this is a crucial concept. When administering immunotherapy, the challenge we often face is the heterogeneity of the disease. While many lesions may respond well, some may continue to progress. Metastasis-directed therapies such as SBRT offer a real opportunity for curative intent. SBRT is equivalent to surgery but is outpatient-based, with high tolerance and effectiveness in controlling the disease. Even if not curative, it can provide a long treatment-free interval, delaying the need for systemic therapies that impact quality of life. I avidly utilize it in various scenarios, such as in patients with progressing lesions while on TKI or HIF2 inhibitors. I collaborate closely with my radiation oncology colleagues for optimal patient care.

Dr. McKay: It is good to hear that. There are multiple opportunities, from oligometastatic to oligoprogressive scenarios.

Dr. Hammers: Indeed, for instance, in cases of oligometastatic disease where only 1 or 2 lesions appear after years of being free of metastatic disease post-nephrectomy, especially in elderly patients, stereotactic radiation alone may be sufficient without initiating systemic therapy immediately.

Dr. Tannir: Most clinical trials mandate discontinuation of therapy upon disease progression, which can be challenging when only a few sites are affected. Incorporating metastasis-directed therapy like SBRT enables continuation of systemic therapy, even when there’s localized progression. For example, in patients responding well to nivo/ipi but showing growth in specific sites, SBRT can be directed to those areas while maintaining systemic therapy. Similarly, for patients with resolved metastatic sites but with a primary tumor, surgery might be considered, recognizing the different responses between primary and metastatic lesions. Collaboration among specialties is essential in such cases.

Dr. McKay: Informative insights. Prospective data on SBRT utilization is much needed. Now, regarding variant histologies and non-clear-cell tumors, how do you factor histology into decision-making for IO/IO or IO/TKI?

Dr. Beckermann: Sarcomatoid features serve as a crucial biomarker for IO/IO use. When encountering such features in pathology, initiating IO/IO therapy is a priority. However, the challenge lies in the heterogeneous nature of various histologies. Ideally, we would tailor treatments based on molecular profiles, but this remains a challenge due to the diverse biology of these tumors. Currently, in papillary histology, TKI/IO regimens hold the highest level of evidence, especially in cases with a high disease burden.

Dr. Hammers: Histology plays a significant role in treatment decisions. For instance, in chromophobe carcinoma, which typically does not respond well to immunotherapy, I may still consider it if sarcomatoid differentiation is present. While it is encouraging that some non-clear-cell tumors respond reasonably well to clear-cell targeted therapies, there is a need for more tailored approaches.

Dr. Tannir: It’s time to shift towards referring to these tumors as variant histologies rather than non-clear-cell, acknowledging their distinct identities. Designing trials grounded in the biology of each tumor type is crucial. By collaborating with industry and patient advocacy groups, we can develop targeted therapies and conduct trials specific to these histologies. This approach has shown success, even with rare tumors like renal medulla carcinoma, where trials have led to significant enrollment and promising outcomes. This can happen when, as they say, build it and they will come.