Isolated Pancreatic Metastases of Renal Cell Carcinoma—A Paradigm of a Seed and Soil Mechanism: A Literature Analysis of 1,034 Observations

Abstract

Previously documented arguments, in favor of the suspected impact of a seed and soil mechanism, in the development and progression of isolated pancreatic metastasis of renal cell carcinomas (isPM) are: (1) uniform and independent from the side of the primary tumor distribution of isPM within the pancreas and, (2) the similar survival rates for singular and multiple isPM. In addition, the present study adds new arguments that further confirm the importance of an seed and soil mechanism in isPM: (1) Within the singular isPM, the size of the metastasis does not affect the overall survival; (2) Within the group of multiple isPMs, the overall survival does not depend on the number of metastases; (3) For synchronous and metachronous isPM, survival rates are also not different, and (4) Within the group of metachronous isPM there is also no correlation between the overall survival and interval until metastases occurs. This unusual ineffectiveness of otherwise known risk factors of solid cancers can be explained plausibly by the hypothesis of a very selective seed and soil mechanism in isPM. It only allows embolized renal carcinoma cells in the pancreas to complete all steps required to grow into clinically manifest metastases. In all other organs, on the other hand, the body is able to eliminate the embolized tumor cells or at least put them into a dormant state for many years. This minimizes the risk of occult micrometastases in distant organs, which could later-after isPM treatment-grow into clinically manifest metastases, so that the prognosis of the isPM is only determined by an adequate therapy of the pancreatic foci, and prognostic factors, such as total tumor burden or interval until the occurrence of the isPM remain ineffective.

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

“…IsPMRCC are rare observations in which singular or multiple, synchronous or metachronous to the RCC distant metastases occur definitely or over a longer period exclusively in the pancreas. Since the last literature overview ( n = 1034) covering the years 1952 to 2019 [ 51 ] a further 173 isPMRCC observations could be added [ 27 , 28 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. These 1207 observations serve as a basis for a literature review with meta-analysis.…”

“…In addition to the sole occurrence of PM, the clinical course is further characterised by: (1) a long interval between primary RCC therapy and the occurrence of PM. An interval of 9.6 (SD 6.8) years was calculated from 470 individually documented observations [ 28 , 51 , 52 , 53 , 55 ]. In single institution reports [ 27 , 30 , 32 , 33 , 34 , 39 , 40 , 41 , 44 , 47 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ], values from 5.3 [ 34 ] to 14 years [ 27 ] are documented ( Table S1 ); the longest interval reported so far is 36 years [ 81 ]; (2) the frequent occurrence of multiple PM: Of 592 documented cases, 39.2% were multiple PM, with a mean of 3.1 pancreatic foci [ 82 ] and a maximum of 15 foci [ 28 ], and in large case compilations [ 27 , 30 , 33 <...>…”

“…Since these data have already been published [ 20 , 51 , 82 ] they are presented here in an abbreviated form. The exclusive occurrence of metastasis in the pancreas is difficult to reconcile with a systemic haematogenous tumour cell seeding at first glance.…”

“…To clarify the question of a greater significance of a systemic or a local MP, epidemiological investigations are suitable [ 51 ]. Since the local MP should offer for right-sided RCC a greater chance of metastasis in the near caput pancreatis, while for left-sided RCC the chance of metastasizing into the nearby corpus and cauda region is greater, a dependence of metastasis localisation in the pancreas from the RCC side should result.…”

“…Conversely, diffuse cell spread in a systemic haematogenous pathway should lead to a distribution pattern of PM independent of the RCC side. The epidemiological data demonstrate a uniform distribution of metastases in the pancreas [ 51 ] and in particular a significant independence of the distribution from the side of the primary RCC ( Table 1 ). This result has now also been confirmed in large single and multicentre studies [ 30 , 35 , 38 , 43 , 69 ].…”