How would you approach adjuvant systemic therapy for an isolated, oligometastatic CNS recurrence of RCC that was treated with SBRT?

I tend not to treat patients with resected/irradiated CNS lesion(s) if there is no disease elsewhere. Such patients were not included in the adjuvant pembro study, the activity of any systemic therapy for CNS disease is not well-established, and in general, I worry single agent pembro is undertreatment for M1 disease. Also, this is due to the fact that there is no way to assess whether the systemic therapy is helping the patient. The good news is that local control of CNS mets is 90% after SBRT so monitoring with appropriate doublet therapy upon further progression is reasonable.

KEYNOTE-564 study led to the approval of adjuvant pembrolizumab in patients with high-risk RCC, including those who had metastatectomy (M1-NED) (Choueiri et al., PMID 34407342). But, the trial excluded patients with brain and bone metastases. Therefore, there is no evidence-based guidance in this scenario. Brain metastasis is a poor prognostic marker in RCC and often predicts recurrence in other sites. Although locally ablative therapy is considered a standard of care in many RCC patients with oligometastatic recurrence, the outcome is generally worse for CNS metastases compared to other sites and progression is likely (Mikhail et al., PMID 35965871).

I therefore prefer to treat those patients with systemic therapy taking into consideration...

Brain metastases (BM) are a challenging manifestation of renal cell carcinoma and patients with brain metastases from renal cell carcinoma (RCC) have been underrepresented in clinical trials. In the absence of consensus guidelines and prospective data, one has to rely on retrospective experience.

For patients who have single or multiple small BMs (all amenable to locoregional therapy) and no evidence of disease outside the CNS, such as a patient who is several years out from nephrectomy with an isolated recurrence in the CNS, it is reasonable to consider monitoring with interval imaging alone, without systemic therapy, after the completion of locoregional therapy. On the contrary, for patients with excellent performance status who develop BM...