Prognostic Significance of Pancreatic Metastases in Patients With Advanced Renal Cell Carcinoma Treated With Systemic Therapy

Shaya, Justin; Lin, Xun; Weise, Nicole; Cabal, Angelo; Panian, Justine; Derweesh, Ithaar; McKay, Rana R.

doi:10.1016/j.clgc.2021.04.006

Cited by 6 publications

(5 citation statements)

References 20 publications

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“…However, not only isolated PM of the RCC is characterized by a protracted course with a favourable prognosis. Additionally, in multiple organ site metastases of the RCC, the presence of PM signals a more favourable course, as Grassi et al [261] pointed out for the first time and as confirmed by several studies [238,[262][263][264][265][266][267],. Whether the favourable results in isolated PM and in PM in the course of generalization stages are based on the same pathomechanism in different degrees of severity is currently unclear.…”

Section: Genetics/epigenetics Of Ispmrccmentioning

confidence: 68%

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

Sellner

Thalhammer

Klimpfinger

2023

Cancers

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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.

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Section: Genetics/epigenetics Of Ispmrccmentioning

confidence: 68%

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

Sellner

Thalhammer

Klimpfinger

2023

Cancers

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“…Prolonged OS of mRCC to the pancreas is well documented with previous reports of OS of 42–106 months. 5 , 8 , 18 , 19 This is in contrast with shorter OS for mRCC patients in general, with the longest median OS currently reported at 57.7 months. 2 , 3 , 20 …”

Section: Discussionmentioning

confidence: 92%

“… 2 , 3 Renal cell carcinoma (RCC) patients with endocrine metastases, specifically pancreatic disease, have prolonged OS compared to patients with non-endocrine metastases. 1 , 4 , 5 Pancreatic metastases are uncommon, seen in only two to five percent of all malignancies including RCC, melanomas, colorectal carcinomas, breast cancers, and sarcomas. 6 , 7 RCC is the most common primary tumor leading to pancreatic metastases, with pancreatic metastases found in three to ten percent of metastatic RCC cases.…”

Section: Introductionmentioning

confidence: 99%

Metastatic renal cell carcinoma to the pancreas and other sites—a multicenter retrospective study

Duarte,

Hu,

Beuselinck

et al. 2023

eClinicalMedicine

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“…PBRM1 is the most frequently mutated gene after VHL [84,92] and mutations acquired in this gene largely do not overlap with loss of function mutations in BAP1 [58,88,90,92,96]. PBRM1 mutations are associated with improved outcome in ccRCC [95,97] and do not correlate with decreased survival [88], whereas the absence of mutations of PBRM1 resulted in worse outcome [90]. KDM5C mutations have also been associated with improved clinical outcome in clinical reports [88,94].…”

Section: Genetic Characteristics and Peculiarities Of The Ispmrcc 21 ...mentioning

confidence: 99%

“…The isPMRCC showed an independent genetic profile characterized by the absence of 9p loss and a significantly lower genome instability index: Despite a 15-year and 8-year interval between primary ccRCC and clinical manifestation of PM, only one additional driver mutation was observed in two cases (mTor and SETD2, respectively) and in the third case, even after 17 years, there was no additional driver event to prove. (b) Based on the improved prognosis of multiorgan metastases of ccRCC with concurrent PM compared to cases without PM, as shown by Grassi [105], and since repeatedly confirmed [11,91,97,[106][107][108][109][110], Singla and colleagues in 2020 focused on the question of genetic characteristics of PM in mRCC [91]. (Their study group included 31 patients, but only a subgroup of just 10 (32%) met the isPMRCC criteria.…”

Section: Genetic Profile Of Ispmrccmentioning

confidence: 99%

Genetic and Epigenetic Characteristics in Isolated Pancreatic Metastases of Clear-Cell Renal Cell Carcinoma

Sellner,

Compérat,

Klimpfinger

2023

IJMS

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Isolated pancreatic metastases of renal cell carcinoma (IsPMRCC) are a rare manifestation of metastatic, clear-cell renal cell carcinoma (RCC) in which distant metastases occur exclusively in the pancreas. In addition to the main symptom of the isolated occurrence of pancreatic metastases, the entity surprises with additional clinical peculiarities: (a) the unusually long interval of about 9 years between the primary RCC and the onset of pancreatic metastases; (b) multiple pancreatic metastases occurring in 36% of cases; (c) favourable treatment outcomes with a 75% 5-year survival rate; and (d) volume and growth-rate dependent risk factors generally accepted to be relevant for overall survival in metastatic surgery are insignificant in isPMRCC. The genetic and epigenetic causes of exclusive pancreatic involvement have not yet been investigated and are currently unknown. Conversely, according to the few available data in the literature, the following genetic and epigenetic peculiarities can already be identified as the cause of the protracted course: 1. high genetic stability of the tumour cell clones in both the primary tumour and the pancreatic metastases; 2. a low frequency of copy number variants associated with aggressiveness, such as 9p, 14q and 4q loss; 3. in the chromatin-modifying genes, a decreased rate of PAB1 (3%) and an increased rate of PBRM1 (77%) defects are seen, a profile associated with a favourable course; 4. an increased incidence of KDM5C mutations, which, in common with increased PBRM1 alterations, is also associated with a favourable outcome; and 5. angiogenetic biomarkers are increased in tumour tissue, while inflammatory biomarkers are decreased, which explains the good response to TKI therapy and lack of sensitivity to IT.

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Prognostic Significance of Pancreatic Metastases in Patients With Advanced Renal Cell Carcinoma Treated With Systemic Therapy

Cited by 6 publications

References 20 publications

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

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

Metastatic renal cell carcinoma to the pancreas and other sites—a multicenter retrospective study

Genetic and Epigenetic Characteristics in Isolated Pancreatic Metastases of Clear-Cell Renal Cell Carcinoma

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