Isolated Pancreatic Metastases of Renal Cell Carcinoma—Clinical Particularities and Seed and Soil Hypothesis

Abstract

A meta-analysis of 1470 isolated pancreatic metastases of renal cell carcinoma revealed, that, in addition to the unusual exclusive occurrence of pancreatic metastases and the favourable treatment results, the isPMRCC is characterised by further peculiarities of the clinical course: The lack of prognostic significance of volume and growth rate dependent risk factors and the independence of treatment results from standard or local resections. As an explanation for all these peculiarities, according to today’s knowledge, a strong acting seed and soil mechanism can serve, which allows embolized tumour cells to grow to metastases only in the pancreas, and prevents them definitively or for years in all other organs. The good prognosis affects not only isolated PM, but also multi-organ metastases of the RCC, in which the additional occurrence of PM is also associated with a better prognosis. Genetic studies revealed specific changes in cases of PM of RCC: Lack of loss of 9p21.3 and 14q31.2, which are otherwise specific gene mutations at the onset of generalization, a low weight genome instability index, i.e., high genetic stability, and a low rate of PAB1 and a high rate of BPRM1 alterations, which signal a more favourable course. The cause of pancreatic organotropism in isPMRCC is still unclear, so only those factors that have been identified as promoting organotropism in other, more frequent tumour entities can be presented: Formation of the pre-metastatic niche, chemokine receptor–ligand mechanism, ability to metabolic adaptation, and immune surveillance.

Comments on and Illustrations of the EFSUMB CEUS Guidelines: Transabdominal and Endoscopic Ultrasound Features of Intrapancreatic Metastases and the Role of Multiparametric Imaging and EUS-Guided Sampling in Rare Pancreatic Tumors

“…The most common intrapancreatic RCC metastases are those of the clear cell subtype [45]. The striking differences between the relative frequency of RCC metastases between surgical and autopsy cohorts may be explained by their rather good prognosis and often solitary occurrence, which makes these patients more likely to qualify for pancreatic resection than those with pancreatic metastases from other primary tumors [22,39,43,46,47].…”

“…Sellner et al calculated cumulative 5-year and 10-year survival rates of 75.7% and 47.3%, respectively, from 415 casuistically reported postoperative observations in RCC pancreatic metastases [42]. According to the meta-analyses of Adler et al, Huang et al, and Sellner et al, none of the following factors significantly influence treatment outcomes: singular or multiple localization of RCC metastases; synchronous or a metachronous occurrence; the interval to nephrectomy; size of metastases [33,39,41,43,46]. Nevertheless, Rodger et al, in their most current systematic review of 35 cohort studies, reported that a metachronous presentation and a longer disease free interval before the presentation of intrapancreatic metastases were significantly associated with better survival outcomes [105].…”

“…Nevertheless, Rodger et al, in their most current systematic review of 35 cohort studies, reported that a metachronous presentation and a longer disease free interval before the presentation of intrapancreatic metastases were significantly associated with better survival outcomes [105]. Interestingly, even patients with isolated intrapancreatic RCC metastases who have foregone active therapy have a relatively favorable 3-year survival rate of 56%, although this is significantly worse compared to patients undergoing curatively intended therapy [46]. Blanco-Fernandez et al reported postoperative overall survival rates at 1, 3, and 5 years of 96%, 88%, and 83%, respectively [56].…”

Metastatic Kidney Cancer: Does the Location of the Metastases Matter? Moving towards Personalized Therapy for Metastatic Renal Cell Carcinoma

“…On the other hand, patients with metastases to the liver, bones, and brain tend to have the worst prognosis. However, patients with endocrine metastases, such as pancreatic metastases, even though rare, exhibit a significantly prolonged disease course and a better outcome [12][13][14][15].…”

Beyond the Knife in Renal Cell Carcinoma: A Systematic Review—To Ablate or Not to Ablate?

“…Side-effects of targeted agents may include, but are not limited to, diarrhoea, skin effects, and lethargy, whereas more inflammatory side-effects are seen with IO including pneumonitis, colitis, and hormone dysfunction. Furthermore, as patients are living longer, the patterns of failure have also altered with more RCC patients presenting with issues of LC from poorly responding and progressive local disease or metastasis [ 33 , 34 , 35 ]. Many patients cannot have surgical resection, due to either technical feasibility or patient factors.…”