Clinical Impact of Pancreatic Metastases from Renal Cell Carcinoma: A Multicenter Retrospective Analysis

Paolo Grassi, Ludovic Doucet, Palma Giglione, Viktor Grünwald, Bohuslav Melichar, Luca Galli, Ugo De Giorgi, Roberto Sabbatini, Cinzia Ortega, Matteo Santoni, Aristotelis Bamias, Elena Verzoni, Lisa Derosa, Hana Studentova, Monica Pacifici, Jorgelina Coppa, Vincenzo Mazzaferro, Filippo de Braud, Camillo Porta, Bernard Escudier, Giuseppe Procopio, Paolo Grassi, Ludovic Doucet, Palma Giglione, Viktor Grünwald, Bohuslav Melichar, Luca Galli, Ugo De Giorgi, Roberto Sabbatini, Cinzia Ortega, Matteo Santoni, Aristotelis Bamias, Elena Verzoni, Lisa Derosa, Hana Studentova, Monica Pacifici, Jorgelina Coppa, Vincenzo Mazzaferro, Filippo de Braud, Camillo Porta, Bernard Escudier, Giuseppe Procopio

Abstract

Pancreatic metastases from renal cell carcinoma are uncommon and their prognostic significance is not well defined. In this analysis we evaluated the outcome of patients with pancreatic metastases treated with either targeted therapies or local treatment to the pancreas. Patients with pancreatic metastases from renal cell carcinoma treated between 1993 and 2014 were identified from 11 European centers. Clinical records were retrospectively reviewed. Kaplan-Meier method and log-rank test were used to evaluate progression-free survival and overall survival. Cox's proportional hazard models were used for survival analysis. In total, 276 PM patients were evaluated, including 77 (28%) patients treated by either surgery or radiotherapy to the pancreas, and 256 (93%) who received systemic therapy. Median time from nephrectomy to diagnosis of pancreatic metastases was 91 months (IQR 54-142). Disease control rate after first-line TTs was 84%, with a median progression-free survival of 12 months (95% CI 10-14). Median overall survival was 73 months (95% CI 61-86) with a 5-year OS of 58%. Median OS of patients treated with local treatment was 106 months (95% CI 78-204) with a 5-year overall survival of 75%. On multivariable analysis, nephrectomy (HR 5.31; 95%CI 2.36-11.92; p<0.0001), Memorial Sloan Kettering/International Metastatic RCC Database Consortium prognostic score (HR 1.45, 95% CI 0.94-2.23 for intermediate vs good vs risk; HR 2.76 95%, CI 1.43-5.35 for poor vs good risk p = 0.0099) and pancreatic local treatment (HR 0.48; 95%CI 0.30-0.78 p = 0.0029) were associated with overall survival. Difference in median OS between patients with PM and that reported in a matched-control group of mRCC patients with extrapancreatic metastases was statistically significant (p < .0001). Pancreatic metastases from renal cell carcinoma usually occur years after nephrectomy, are associated with an indolent behavior and a prolonged survival. Targeted therapies and locoregional approaches are active and achieve high disease control rate.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Overall survival calculated from PM…
Fig 1. Overall survival calculated from PM manifestation to death.
Fig 2. Overall survival calculated from initiation…
Fig 2. Overall survival calculated from initiation of first-line TTs for PM patients and the control group.
Fig 3. Overall survival in the entire…
Fig 3. Overall survival in the entire study population according to Memorial Sloan Kettering Cancer Center prognostic risk score.
Fig 4. Overall survival for patients who…
Fig 4. Overall survival for patients who underwent pancreatic local treatment (surgery or radiation therapy) and in those who received TTs only.

References

    1. Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. New England Journal of Medicine. 1996; 335 (12): 865–875.
    1. Sohn TA, Yeo CJ, Cameron JL, Nakeeb A, Lillemoe KD. Renal cell carcinoma metastatic to the pancreas: results of surgical management. Journal of Gastrointestinal Surgery. 2001; 5: 346–351.
    1. Ballarin R, Spaggiari M, Cautero N De Ruvo N, Montalti R, Longo C et al. Pancreatic metastases from renal cell carcinoma: the state of the art. World Journal of Gastroenterology 2011; 17:4747–4756. 10.3748/wjg.v17.i43.4747
    1. Wente MN, Kleeff J, Esposito I, Hartel M, Müller MW, Fröhlich BE, et al. Renal cancer cell metastasis into the pancreas: a single-center experience and overview of the literature. Pancreas 2005; 30:218–222.
    1. Thompson LD, Heffess CS. Renal cell carcinoma to the pancreas in surgical pathology material. Cancer 2000; 89:1076–1088.
    1. Law CH, Wei AC, Hanna SS, Al-Zahrani M, Taylor BR, Greig PD, et al. Pancreatic resection for metastatic renal cell carcinoma: presentation, treatment, and outcome. Annals of Surgical Oncology 2003; 10:922–926.
    1. Sellner F, Tykalsky N, De Santis M, Pont J, Klimpfinger M. Solitary and multiple isolated metastases of clear cell renal carcinoma to the pancreas: an indication for pancreatic surgery. Annals of Surgical Oncology 2006; 13:75–85.
    1. Grassi P, Verzoni E, Mariani L De Braud F, Coppa J, Mazzaferro V, et al. Prognostic role of pancreatic metastases from renal cell carcinoma: results from an Italian center. Clinical Genitourinary Cancer 2013; 11:484–488. 10.1016/j.clgc.2013.04.022
    1. Bassi C, Butturini G, Falconi M, Sargenti M, Mantovani W, Pederzoli P. High recurrence rate after atypical resection for pancreatic metastases from renal cell carcinoma. British Journal of Surgery 2003; 90: 555–559.
    1. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. New England Journal of Medicine 2007; 356: 115–124.
    1. Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. TARGET Study Group. TARGET Study Group Sorafenib in advanced clear-cell renal-cell carcinoma. New England Journal of Medicine 2007; 356: 125–134.
    1. Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. Journal of Clinical Oncology 2010; 28:1061–1068. 10.1200/JCO.2009.23.9764
    1. Rini BI, Escudier B, Tomczak P Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase III trial. Lancet 2011; 378:1931–1939. 10.1016/S0140-6736(11)61613-9
    1. Hudes G, Carducci M, Tomczak P Dutcher J, Figlin R, Kapoor A, et al. (2007). Global ARCC Trial. Global ARCC Trial Temsirolimus, interferon alfa or both for advanced renal-cell carcinoma. New England Journal of Medicine 2007; 356:2271–2281.
    1. Motzer RJ, Escudier B, Oudard S Hutson TE, Porta C, Bracarda S, et al. RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008; 372:449–456. 10.1016/S0140-6736(08)61039-9
    1. Escudier B, Pluzanska A, Koralewski P Ravaud A, Bracarda S, Szczylik C et al. AVOREN Trial investigators. Bevacizumab plus interferon alfa-2 for treatment of metastaic renal cell carcinoma: a randomised, double blind phase III trial. Lancet 2007; 370:2103–2111.
    1. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. Journal of Clinical Oncology 1999; 17:2530–2540.
    1. Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. Journal of Clinical Oncology 2009; 27:5794–5799. 10.1200/JCO.2008.21.4809
    1. McKay RR, Kroeger N, Xie W, Lee JL, Knox JJ, Bjarnason GA, et al. Impact of bone and liver metastases on patients with renal cell carcinoma treated with targeted therapy. European Urology 2014; 65:577–584. 10.1016/j.eururo.2013.08.012
    1. Grassi P, Verzoni E, Porcu L, Testa I, Iacovelli R, Torri V, et al. Targeted therapies in advanced renal cell carcinoma: the role of metastatic sites as a prognostic factor. Future Oncology 2014; 10:1361–1372. 10.2217/fon.14.69
    1. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. New England Journal of Medicine 2012; 366:883–892. 10.1056/NEJMoa1113205
    1. Ghavamian R, Klein KA, Stephens DH, Welch TJ, LeRoy AJ, Richardson RL, et al. Renal cell carcinoma metastatic to the pancreas: clinical and radiological features. 2000; 75:581–585.
    1. Santoni M, Conti A, Procopio G, Porta C, Ibrahim T, Barni S, et al. Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis? Journal of Expert Clinical Cancer Research 2015; 34:10
    1. Beuselinck B, Oudard S, Rixe O Wolter P, Blesius A, Ayllon J, et al. Negative impact of bone metastasis on outcome in clear-cell renal cell carcinoma treated with sunitinib. Annals of Oncology 2011; 22:794–800. 10.1093/annonc/mdq554
    1. Albiges L, Choueiri T, Escudier B, Galsky M, George D, Hofmann F, et al. A systematic review of sequencing and combinations of systemic therapy in metastatic renal cancer. European Urology 2015; 67:100–110. 10.1016/j.eururo.2014.04.006
    1. Santoni M, Conti A, Partelli S, Porta C, Sternberg CN, Procopio G, et al. Surgical Resection Does Not Improve Survival in Patients with Renal Metastases to the Pancreas in the Era of Tyrosine Kinase Inhibitors. Annals of Surgical Oncology 2014l; 22(6): 2094–2100.
    1. Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nature Reviews Cancer 2002; 2:563–572.
    1. Zerbi A, Ortolano E, Balzano G, Borri A, Beneduce AA, Di Carlo V. Pancreatic metastasis from renal cell carcinoma: which patients benefit from surgical resection? Annals of Surgical Oncology 2008; 15:1161–68. 10.1245/s10434-007-9782-0
    1. Tanis PJ, van der Gaag NA, Busch OR, van Gulik TM, Gouma DJ. Systematic review of pancreatic surgery for metastatic renal cell carcinoma. British Journal of Surgery 2009; 96:579–592. 10.1002/bjs.6606
    1. Kalra S, Atkinson BJ, Matrana MR, Matin SF, Wood CG, Karam JA, et al. Prognosis of patients with metastatic renal cell carcinoma and pancreatic metastases. British Journal of Urology International 2015. June 1; 10.1111/bju.13185 [Epub ahead of print].

Source: PubMed

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