(UroToday.com) In the eleventh session of the 2022 International Kidney Cancer Symposium (IKCS): Europe meeting focusing on the role of radiotherapy for kidney cancer, Dr. Scorsetti presented on the role of radiotherapy in patients with oligometastatic renal cell carcinoma (RCC).
Dr. Scorsetti began by discussing the context of the oligometastatic setting, which was first described in 1995. Since that time, there has been a burgeoning literature though there have been no agree for numerous important features. This prompted recent consensus work on oligometastatic disease. A recent consensus document from ESMO-ESTRO specifically defined oligometastatic disease was one to five metastatic lesions, with or without control of the primary tumor. Notably, the group required that all metastatic sites be amenable to safe treatment.
Despite this consensus definition, she emphasized that the oligometastatic disease setting is highly heterogeneous population including patients with solitary or multifocal disease, those with synchronous and metachronous presentations, those with oligorecurrence following prior therapy, and those with oligoprogression on therapy. To better characterize and classify oligometastatic disease, ESTRO and EORTC recently undertook a consensus process using the Delphi consensus method.
In this context, Dr. Scorsetti discussed the role of stereotactic body radiotherapy (SBRT) as an “alternative to more invasive treatment approaches”. SBRT is an external beam radiotherapy approach which precisely delivers ablative doses of radiotherapy in a limited number of fractions. Compared to conventional radiotherapy, SBRT has increased efficacy and reduced normal tissue toxicity. In the context of metastatic disease, SBRT seeks to ablate a limited burden of disease in order to either delay the onset of systemic therapy in patients with oligorecurrent disease or delay systemic therapy intensification or switch in patients with oligoprogressive disease. In the context of oligometastatic kidney cancer, there are numerous studies of this SBRT approach, though they are limited in terms of methodology.
She first emphasized data from her own center examining 73 lesions in 58 patients, the majority of which were in the lungs (53%) and lymph nodes (26%). This works showed good local control, however, most patients progressed outside the field of radiation. Both a metachronous presentation and a single site of metastasis were associated with better progression-free survival.
She highlighted two cases, including patients with a solitary lung metastasis and with abdominal lymphadenopathy. In each of these cases, she demonstrated significant and prolonged responses.
To guide selection of patients for this approach, Dr. Scorsetti’s group undertook work to define a risk classification schema, utilizing data from 129 patients treated for 242 metastatic sites. They found four risk groups defined on the basis of the disease location and a history of bony metastatic disease.
As may be expected, further work has shown that those patients who had complete SBRT (defined as treatment of all sites of disease), had significantly longer progression-free survival and cancer specific survival.
In addition to this work assessing SBRT in isolation, there have been numerous studies assessing the combination of SBRT with systemic therapy. For the most part these have been very small studies (5-50 patients) and most are retrospective. While most of these studies have examined SBRT combined with tyrosine kinase inhibitors only, a recent publication including 17 patients of whom 5 received nivolumab therapy. Overall, response rates were 76% with 5 patients having a complete response in the SBRT target. Perhaps as importantly, treatment was well tolerated. In related works from the Italian Association of Radiotherapy and Clinical Oncology, there was no correlation between the use of systemic therapy during SBRT and either acute or late toxicity. Further, overall toxicity was low.
In combination with tyrosine kinase inhibitors, a number of studies that Dr. Scorsetti highlighted have shown favourable outcomes. Not surprisingly, some of this work has shown that patients who experience a complete response following this combined treatment approach have longer progression-free and overall survival rates. Perhaps more importantly, and while limited by a retrospective methodology and small sample size, work from Dr. Liu and colleagues have shown improved median overall survival among patients who received tyrosine kinase inhibitors with TKI compared to those who received TKI alone.
Moving forward, she highlighted two prospective efforts to address this better. The RAPPORT trial is a phase I/II study of SBRT and pembrolizumab in patients with oligometastatic RCC while CYTOSHRINK is a randomized phase II comparison of nivolumab and ipilimumab with or without SBRT in patients with intermediate or poor risk RCC who are not candidates for cytoreductive nephrectomy.
Ending her presentation, Dr. Scorsetti concluded that SBRT is able to ablate a limited burden of disease safely and effectively in oligometastatic RCC. When combined with TKI, this combination approach may improve outcomes compared to systemic therapy alone. Further work will better define its role in combination with modern immunotherapy based regimes.Presented by: Marta Scorsetti, MD, Full Professor in Diagnostic Imaging and Radiotherapy, Humanitas University, Milan, Lombardy, Italy
Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2022 International Kidney Cancer Symposium (IKCS) Europe Annual Hybrid Meeting, Antwerp, Belgium, Fri, Apr 22 – Sun, Apr 24, 2022.