Pancreatic tropism of metastatic renal cell carcinoma

IMPORTANCE There exists considerable biological and clinical variability between histologic variants of metastatic renal cell carcinoma (mRCC). Data reporting on patterns of metastasis in histologic variants of mRCC are sparse.OBJECTIVE To characterize sites of metastasis and their association with survival across the 3 most common histologic variants of mRCC: clear cell (ccRCC), papillary (pRCC), and chromophobe (chrRCC). DESIGN, SETTING, AND PARTICIPANTSIn this multicenter, international cohort study, the International mRCC Database Consortium (IMDC) database was used to identify consecutive patients starting systemic therapy for mRCC between 2002 and 2019. Patients with mixed histologic subtype were excluded. Statistical analysis was performed from February to June 2020. EXPOSURES Data regarding histologic subtype and sites of metastatic involvement at the time of first systemic therapy initiation were collected. MAIN OUTCOMES AND MEASURESThe primary outcomes were prevalence of metastatic site involvement and overall survival (OS) from time of systemic therapy initiation. Patients with multiple sites of metastatic involvement were included in analyses of all groups to which they had metastases. RESULTS A total of 10 105 patients were eligible for analysis. Median (interquartile range) age at diagnosis was 60 (53-67) years, 7310 (72.4%) were men and 8526 (84.5%) underwent nephrectomy. Of these, 9252 (92%) had ccRCC, 667 (7%) had pRCC, and 186 (2%) had chrRCC. The median number of sites of metastasis was 2 (range, 0-7). In ccRCC, the most common sites of metastasis were lung (70%; 6189 of 8804 patients [448 missing]), lymph nodes (45%; 3874 of 8655 patients [597 missing]), bone (32%; 2847 of 8817 patients [435 missing]), liver (18%; 1560 of 8804 [448 missing]), and adrenal gland (10%; 678 of 6673 patients [2579 missing]). Sites of metastasis varied between subtypes. Lung, adrenal, brain, and pancreatic metastases were more frequent in ccRCC, lymph node involvement was more common in pRCC, and liver metastases were more frequent in chrRCC. Median OS for ccRCC varied by site of metastatic involvement, ranging between 16 months (95% CI, 13.7-18.8 months) for the pleura and 50 months (95% CI, 41.1-55.5 months) for the pancreas. Compared with ccRCC, patients with pRCC tended to have lower OS, regardless of metastatic site. CONCLUSIONS AND RELEVANCESites of metastatic involvement differ according to histologic subtype in mRCC and are associated with OS. These data highlight the clinical and biological variability between histologic subtypes of mRCC. Patterns of metastatic spread may reflect (continued) Key Points Question In metastatic renal cell carcinoma (RCC), do patterns of metastasis differ between histologic subtypes and are sites of metastasis associated with survival? Findings In this cohort studyincluding 10 105 patients, patterns of metastasis varied significantly between metastatic clear cell RCC, papillary RCC, and chromophobe RCC. Sites of metastasis were associated with survival in all histologic subtype...

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“…Other groups have also reported on the unique biological profile of ccRCC that has metastasized to the pancreas. 28 …”

Section: Discussionmentioning

confidence: 99%

Evaluation of Clear Cell, Papillary, and Chromophobe Renal Cell Carcinoma Metastasis Sites and Association With Survival

et al. 2021

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“…[21][22][23] Such a long tumor latency may be due to different mutational landscapes and angiogenesis mechanisms relative to metastases at typical sites (lung, bone, liver, and lymph nodes), that mostly occur within 5 years. 16 The available data from patients undergoing surgical resection for PM report favorable outcomes, with 5-year survival rates up to 72%. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] Assuming 10-year survival is a more pertinent outcome measure, given that the disease course is often indolent, we enrolled patients up to 2008 and made sure that all the subjects still living had an adequately updated recurrence and vital information at the time of data lock.…”

Section: Discussionmentioning

confidence: 99%

“…1 The current treatment options include surgical resection [1][2][3][4][5][6][7][8][9][10][11][12][13][14] or newly introduced biologic agents directed at vascular endothelial growth factor receptor (VEGF-R), tyrosine kinases (TK), or mammalian target of rapamycin (mTOR). [15][16][17] Because of the infrequency of PM, it has been particularly challenging to accrue clinical data supporting one strategy over the other, with no randomized trials of resection versus targeted therapy having been conducted to date. When resection is undertaken, the extent depends on the size and the number of metastases.…”

mentioning

confidence: 99%

Long-term Outcomes After Surgical Resection of Pancreatic Metastases from Renal Clear-Cell Carcinoma

et al. 2021

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Background Pancreatic metastases (PM) from renal cell carcinoma (RCC) are uncommon. We herein describe the long-term outcomes associated with pancreatectomy at two academic institutions, with a specific focus on 10-year survival. Methods This investigation was limited to patients undergoing pancreatectomy for PM between 2000 and 2008 at the University of Verona and Memorial Sloan Kettering Cancer Center, allowing a potential for 10 years of surveillance. The probabilities of further RCC recurrence and RCC-related death were estimated using a competing risk analysis (method of Fine and Gray) to account for patients who died of other causes during follow-up. Results The study population consisted of 69 patients, mostly with isolated metachronous PM (77%). The median interval from nephrectomy to pancreatic metastasectomy was 109 months, whereas the median post-pancreatectomy follow-up was 141 months. The 10-year cumulative incidence of new RCC recurrence was 62.7%. In the adjusted analysis, the relative risk of repeated recurrence was significantly higher in PM synchronous to the primary RCC (sHR = 1.27) and in patients receiving extended pancreatectomy (sHR = 3.05). The 10-year cumulative incidence of disease-specific death was 25.5%. The only variable with an influence on disease-specific death was the recurrence-free interval following metastasectomy (sHR = 0.98). In patients with repeated recurrence, the 10-year cumulative incidence of RCC-related death was 35.4%. Conclusion In a selected group of patients followed for a median of 141 months and mostly with isolated metachronous PM, resection was associated with a high possibility of long-term disease control in surgically fit patients with metastases confined to the pancreas.

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“…Gene expression data from IMmotion150, TCGA, and the International Cancer Genome Consortium showed increased angiogenesis signatures among patients with PBRM1 mutations from all three cohorts [ 49 ]. Clinical data from mRCC patients with pancreatic metastases demonstrated PBRM1 mutations were associated with improved response to anti-VEGF therapy, supporting that PBRM1 mutant tumors may have a more angiogenic phenotype [ 50 ]. Additionally, biomarker data from CheckMate 214 presented at ASCO 2020 showed no significant difference in PFS or OS between PBRM1 wild type or mutant within either the nivolumab plus ipilimumab arm or in the sunitinib arm [ 23 ].…”

Section: Polybromo-1 Mutationsmentioning

confidence: 99%

Predicting Response to Immunotherapy in Metastatic Renal Cell Carcinoma

Tucker

Rini

2020

Cancers

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Immunotherapy-based combinations, driven by PD-1, PD-L1, and CTLA-4 inhibitors, has altered the treatment landscape for metastatic renal cell carcinoma (RCC). Despite significant improvements in clinical outcomes, many patients do not experience deep or lasting benefits. Recent efforts to determine which patients are most likely to benefit from immunotherapy and immunotherapy-based combinations have shown promise but have not yet affected clinical practice. PD-L1 expression via immunohistochemistry (IHC) has shown promise in a few clinical trials, although variations in the IHC assays as well as the use of different values for positivity presents unique challenges for this potential biomarker. Several other candidate biomarkers were investigated including tumor mutational burden, gene expression signatures, single gene mutations, human endogenous retroviruses, the gastrointestinal microbiome, and peripheral blood laboratory markers. While individually these biomarkers have yet to explain the heterogeneity of treatment response to immunotherapy, using aggregate information from these biomarkers may inform clinically useful predictive biomarkers.

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Pancreatic tropism of metastatic renal cell carcinoma

Cited by 67 publications

References 64 publications

Evaluation of Clear Cell, Papillary, and Chromophobe Renal Cell Carcinoma Metastasis Sites and Association With Survival

Evaluation of Clear Cell, Papillary, and Chromophobe Renal Cell Carcinoma Metastasis Sites and Association With Survival

Long-term Outcomes After Surgical Resection of Pancreatic Metastases from Renal Clear-Cell Carcinoma

Predicting Response to Immunotherapy in Metastatic Renal Cell Carcinoma

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