First line treatment of pancreatic metastases in metastatic renal cell carcinoma: Insights from the UK Renal Oncology Collaborative (UK ROC)—Tyrosine kinase inhibitors time to shine?
Authors: Crosby Ben , Frazer Ricky Dylan , McGrane John , Challapalli Amarnath , Charnley Natalie , Jiang Xue Yan , Malik Jahangeer , Sharma Anand , Liu Justin , Parslow Dominique , Geldart Tom , Dyke Claire Louise , Tuthill Mark H. , Melendez-Torres G.J. , Mohamed Wael , Moon Niall , Forde Caroline , Jones Eleanor , Ford Victoria , Bahl Amit 
Published: February 2025

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Background:
Pancreatic metastases (PM) are a rare site of spread in metastatic renal cell carcinoma (mRCC). It has been suggested that patients with PM have improved survival outcomes and more angiogenic driven biology than other metastatic sites. We sought to define these outcomes and determine if TKI based combination is the preferred option in the first line treatment approach.
Methods:
UK ROC is a RWE multicentre study from patients starting SACT for mRCC in 17 UK centres. Retrospective analysis of patients with and without PM was performed. Survival data were compared using Kaplan–Meier curves, and the statistical significance of differences in outcome between the groups was assessed with the log‐rank test. Progression-free survival (PFS) and Overall Survival (OS) from the start of first-line therapy and initial diagnosis was assessed using Cox regression analysis comparing single agent TKI, IO/TKI and IO/IO combinations.
Results:
1319 patients were identified, median age of 65. 90 (6.8%) patients within the cohort had PM. Of these 90, 11 patients had pancreatic only metastatic disease. There were no statistical differences in the distribution of the IMDC prognostic group (p=0.194), type of first-line treatment (IO/IO, TKI or TKI/IO) (p=0.189) or age (p=0.079) in patients with and without PM. Interestingly there was a significantly greater proportion of females in the PM group (37.8% vs 28.2%) (p=0.02). Patients with PM had a significantly greater interval from primary diagnosis to the date of first systemic treatment as compared to those without (median: 44 vs 5 months) (p<0.001). As expected, patients with PM in the overall population had improved OS from the primary diagnosis compared to non-PM [70 vs 28 months (HR 0.51, p<0.01)]. Similarly, PFS from diagnosis was significantly prolonged in those with PM (68 vs 19 months, HR 0.44, p<0.01). Importantly patients who have PM who receive either single agent TKI or IO/TKI have a significant improvement in survival compared to those without PM. The same significant improvement is not seen in PM patients who receive IO/IO combinations first line.
Conclusions:
As predicted based upon previous publications, our study demonstrated that patients with PM from RCC have relatively longer survival times than patients with metastatic RCC of other sites. More importantly though for decision making, patients who receive TKI based treatment have an improvement in outcome in patients with PM compared to treatments that do not contain a TKI. This would advocate TKI monotherapy or IO/TKI regimens in this patient group. Clinical trial information:
(REC reference 24/SC/0038) IRAS project ID 338935
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