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

SIMPLE SUMMARY: The occurrence of pancreatic metastases, especially isolated pancreatic metastases (PM) in metastatic renal cell carcinoma, is associated with unusual clinical features—such as favourable prognosis and ineffectiveness of tumour volume and growth rate dependent risk factors. On the other hand, it was hypothesised that the entity of isolated pancreatic metastases should be considered as a pattern of “seed and soil” mechanism. An extensive literature search was conducted to investigate whether and what mechanism links these two observations. The result of the study shows that an unusually strong seed and soil mechanism (SSM), which allows metastases settlement only in the pancreas, inevitably leads to the ineffectiveness of these risk factors in isolated PM. The hypothesis that the entity of isolated PM in renal cell carcinoma (RCC) is to be regarded as a paradigm for an SSM is thus further supported, and the interaction with the two-phased cancer evolutionary model is discussed. ABSTRACT: In metastatic renal cell carcinoma, pancreatic metastases can appear in two clinical manifestations: (a) very rarely as isolated pancreatic metastases and (b) in the context with multi-organ metastatic disease. Both courses are characterised by rare, unusual clinical features. For isolated pancreatic metastases, the literature shows no effect on survival in all 11 publications that examined the effect of singular versus multiple pancreatic metastases; a lack of effect on survival time was also present in all 8 studies on pancreatic metastases size, in 7 of 8 studies on the influence of disease-free interval (DFI), and in 6 of 7 studies on the influence of synchronous versus metachronous metastases. In multi-organ site metastases observations, on the other hand, all five available references showed significantly better results in patients with concurrent pancreatic metastases compared to those without pancreatic metastases, although the total number of affected organs in the pancreatic metastases cohort was larger. Tumour volume-dependent risk factors thus remain surprisingly ineffective in both groups, which contradicts the usual behaviour of solid tumours. The reasons for this unusual behaviour and possible relations to tumour evolution and the hypothesis of an influence of a seed and soil mechanism in the occurrence of pancreatic metastases in metastatic renal cell carcinoma are discussed.