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

Abstract

Abstract. Aim: The study aimed to define the true impact of pancreatic metastases (PM) from renal cell carcinoma on overall survival (OS) in patients treated with first-line tyrosine kinase inhibitors. Patients and Methods: Overall, 321 consecutive patients were analysed. The influence of PM on OS was assessed using the Kaplan-Meier estimator and the logrank test (unadjusted and adjusted) and two multivariabe Cox proportional hazards regressions (CPHR =0.84, p=0.603, and HR=0.66, p=0.098). Conclusion: The presence of PM was not an independent prognostic factor, but was rather an indicator of an indolent course of the disease.Renal cell carcinoma (RCC) is the most frequent type of kidney cancer and accounts for 3% of malignancies in adults. About 20% of patients with RCC have metastases at the initial diagnosis and up to half of patients develop recurrence after complete resection of the primary tumour (1-4). Nowadays, these patients are treated with systemic molecular targeted therapies (MTT) that include tyrosine kinase inhibitors (TKI) as the standard of care in first-line therapy and subsequent lines (5-6). Despite the significant improvement in efficacy of this type of drug compared to cytokine-based regimens, the treatment remains palliative in nature, i.e. aims to maximally increase patient survival with having little curative potential. Moreover, there are still no factors possessing predictive value for MTT, thus patient evaluation and prognosis is made using selected baseline characteristics. The most commonly used and validated tool for survival prediction in patients with metastatic RCC is the International Metastatic Renal Cell Database Consortium (IMDC) model. It consists of six factors independently associated with poor outcome: Karnofsky performance status (KPS) less than 80%, time from diagnosis to start of systemic treatment less than 12 months, haemoglobin level less than the lower limit of normal (LLN), serum corrected calcium level, neutrophil count and platelet count greater than the upper limit of normal (ULN). Patients are stratified into favourable-, intermediate-and poor-risk groups according to the total number of factors (0, 1-2 and 3-6, respectively) (7). Other researchers concluded that the involvement of the metastatic process in specific organs, e.g. liver or bone, as well as an increasing number of metastatic sites may be additional features of reduced survival (8,9). 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 (10-12). It was further suggested that the presence of PM may be considered as an independent factor of favourable prognosis (11-13). This means that PM may increase the probability of survival regardless of the status of other criteria known to have an impact on the prognosis (e.g. those included in t...

Metastatic Tumor Burden and Loci as Predictors of First Line Sunitinib Treatment Efficacy in Patients with Renal Cell Carcinoma

“…It has even been proposed that pancreatic location of metastases is characteristic for RCC tumors with a less aggressive phenotype. We have previously shown that the presence of pancreatic metastases was not an independent prognostic factor in multivariate analysis, but it was an indicator of an indolent course of the disease in the general RCC population 42 .…”

“…In contrast to patients with liver metastases, patients with pancreatic metastases are known to have indolent disease and longer median OS. Reported median OS for patients with pancreatic metastases is 39–46.1 months, while for patients without pancreatic metastases it is 23.1–26 months, but with all other secondary tumor locations 40–42 . It has even been proposed that pancreatic location of metastases is characteristic for RCC tumors with a less aggressive phenotype.…”

Resection of pancreatic metastatic renal cell carcinoma: experience and long-term survival outcome from a large center in China

“…This example illustrates that by closely monitoring blood glucose and providing extra trypsin after total pancreatectomy, the patient could have a better quality of life. In addition to the widely used prognostic factor model from the Memorial Sloan Kettering Cancer Center [ 31 – 33 ], vascular invasion [ 2 ], presence of symptoms [ 34 ], and tumor size more than 3 cm [ 35 ] may be associated with an increased risk of death. However, the localization and number of metastatic lesions have no effect on the site of metastases [ 34 ], which is in line with our current results.…”

Tumour Evolution and Seed and Soil Mechanism in Pancreatic Metastases of Renal Cell Carcinoma

“…In summary, the literature review confirms that clinical prognostic factors that reflect tumour burden and tumour growth rate, such as size, occurrence of multiple metastases, DFI, or synchronous occurrence of PM, which are generally relevant in metastasis surgery of solid carcinomas [136][137][138], remain ineffective with isPMRCC. In particular, the complete lack of influence of the tumour volume on survival contradicts a general concept of cancer, in which a greater tumour burden of the body results in a poorer outcome [139].…”