(UroToday.com) In the fourteenth session of the 2022 International Kidney Cancer Symposium (IKCS): Europe meeting focusing on treatment approaches for patient with non-clear cell renal cell carcinoma (nccRCC), Dr. Giuseppe Procopio discussed treatment approaches for collecting duct and renal medullary carcinoma.
He began by discussing collecting duct carcinoma, a relatively rare (1-3% of all renal neoplasms) tumor arising from the epithelial cells of the collecting duct. Based on genetic profiling, collecting duct carcinoma appears to be a unique entity, distinct from renal cell carcinoma and upper tract urothelial disease. Due to the rarity of this entity, clinical data are scarce and guidance for treatment decisions are limited as they are typically excluded from large randomized controlled trials. As a result, he emphasized that there is a large knowledge gap for the care of patients with these tumors.
Currently, for patients with localized disease, radical nephrectomy is the recommended treatment approach. In contrast, for patients with advanced disease, platinum-based chemotherapy has been the standard of care since 2007 while the role of cytoreductive nephrectomy is relatively controversial. Despite being the standard of care, responses to platinum-based chemotherapy are relatively poor with objective response rates of approximately 25%, median progression-free survival of 7 months, and median overall survival of 10 months.
In contrast to the rapid evolution in treatment options that we have seen for patients with clear cell renal cell carcinoma over the past 15 years, there has been a relative paucity for patients with collecting duct carcinoma.
However, just published in 2022, the BONSAI trial provided phase II single arm prospective data supporting the role of frontline cabozantinib in patients with metastatic collecting duct carcinoma. Accrued between January 2018 and November 2020, this trial demonstrated an objective response rate of 35%. To highlight the clinical value of these data, Dr. Procopio presented a clinical case in which cabozantinib provided a 10 month progression-free survival benefit and the patient lived approximately 3 years from the time of diagnosis of metastatic collecting duct carcinoma. Moving forward, he emphasized the need for prospective trials to better define treatment according to tumor signatures.
He then transitioned to discussion renal medullary carcinoma, another rare cancer (accounting for 0.1% of all renal tumors). Renal medullary carcinoma has an even worse prognosis, with a median overall survival of 4 to 5 months. This condition was first described among young patients with sickle cell disease. Current treatments to date including platinum-based chemotherapy though the evidence base is relatively poor.
Interestingly, as with collecting duct carcinoma, genomic alterations in renal medullary carcinoma differ substantially from clear cell RCC with few target alterations in tyrosine kinase receptor or mTOR pathways. Further, relatively low tumor mutational burden and the absence of microsatellite instability suggest an intrinsic resistance to immunotherapy.
However, these tumors may have SMARCB1 mutations which lead to high MYC expression and replicative stress that may sensitize them to PARP inhibition. To date, h
Contrasting his opinions with the 2019 ESMO guidelines, he suggested that cabozantinib (for collecting duct) and platinum based chemotherapy (for both entities) should be considered for patients with collecting duct and renal medullary carcinomas. However, the evidentiary base for this is relatively poor and there remain few therapeutic options for patients with these aggressive tumors.Presented by: Giuseppe Procopio, MD, Fondazione IRCCS Istituto Nazionale dei Tumori
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.