Clinical Impact of Pancreatic Metastases from Renal Cell Carcinoma: A Multicenter Retrospective Analysis

Abstract

Pancreatic metastases from renal cell carcinoma are uncommon and their prognostic significance is not well defined. In this analysis we evaluated the outcome of patients with pancreatic metastases treated with either targeted therapies or local treatment to the pancreas. Patients with pancreatic metastases from renal cell carcinoma treated between 1993 and 2014 were identified from 11 European centers. Clinical records were retrospectively reviewed. Kaplan-Meier method and log-rank test were used to evaluate progression-free survival and overall survival. Cox’s proportional hazard models were used for survival analysis. In total, 276 PM patients were evaluated, including 77 (28%) patients treated by either surgery or radiotherapy to the pancreas, and 256 (93%) who received systemic therapy. Median time from nephrectomy to diagnosis of pancreatic metastases was 91 months (IQR 54–142). Disease control rate after first-line TTs was 84%, with a median progression-free survival of 12 months (95% CI 10–14). Median overall survival was 73 months (95% CI 61–86) with a 5-year OS of 58%. Median OS of patients treated with local treatment was 106 months (95% CI 78–204) with a 5-year overall survival of 75%. On multivariable analysis, nephrectomy (HR 5.31; 95%CI 2.36–11.92; p<0.0001), Memorial Sloan Kettering/International Metastatic RCC Database Consortium prognostic score (HR 1.45, 95% CI 0.94–2.23 for intermediate vs good vs risk; HR 2.76 95%, CI 1.43–5.35 for poor vs good risk p = 0.0099) and pancreatic local treatment (HR 0.48; 95%CI 0.30–0.78 p = 0.0029) were associated with overall survival. Difference in median OS between patients with PM and that reported in a matched-control group of mRCC patients with extrapancreatic metastases was statistically significant (p < .0001). Pancreatic metastases from renal cell carcinoma usually occur years after nephrectomy, are associated with an indolent behavior and a prolonged survival. Targeted therapies and locoregional approaches are active and achieve high disease control rate.

Prognostic Significance of Pancreatic Metastases from Renal Cell Carcinoma in Patients Treated with Tyrosine Kinase Inhibitors

“…The median time to PM development was almost 10 years from initial diagnosis and was peculiar to this organ. In line with other reports, patients in the PM group had a longer interval from diagnosis to TKI initiation (12), greater number of metastatic sites (12), more frequent contralateral kidney metastases (11,19) and favourable risk group assignment (10)(11)(12), but also less frequent Fuhrman grade 3-4 and bone metastases (10) (12).…”

“…As no predictive markers have been discovered for those therapies, the proper identification of baseline features independently influencing survival is essential in routine patient evaluation and fair stratification in prospective interventional trials. Within numerous factors affecting the prognosis, the presence of PM was reported to reduce the probability of death in several studies (10)(11)(12)(13). This surprising conclusion contradicts a general concept of cancer, in which greater malignant involvement of the body results in poorer outcomes.…”

“…This is obviously a rational concept that a higher burden of malignant disease usually results in faster progression and death. In contrast to this observation, a few studies reported that patients with pancreatic metastases (PM) lived significantly longer than patients with metastases at sites other than the pancreas (10)(11)(12). It was further suggested that the presence of PM may be considered as an independent factor of favourable prognosis (11)(12)(13).…”

Outcome of Patients with Renal Cell Carcinoma and Multiple Glandular Metastases Treated with Targeted Agents

“…Only limited data are available on the outcome of PM from RCC patients presenting with concomitant metastases to other glands treated with targeted agents [7] . Glands represent uncommon metastatic sites from RCC [6,9] . In the present analysis, MGM patients reported a longer survival as compared to patients in the control group.…”

“…However, due to the lack of predictive biomarkers of response, these nomograms give information of prognostic relevance but still appear incomplete and suitable for further refinement in order to provide more accurate information for patient selection. Glandular metastases (GM), in particular pancreatic metastases (PM) were reported to be associated with a more favorable outcome [3,6,7] based on retrospective data from heterogeneous patient populations. This retrospective multicenter analysis investigated the clinical outcome in a cohort of consecutive mRCC patients presenting with multiple metastases to glandular sites treated with TTs at 11 European cancer centers.…”