Prognosis of patients with metastatic renal cell carcinoma and pancreatic metastases Sarathi Kalra*, Bradley J. Atkinson*, Marc Ryan Matrana†, Surena F. Matin*, Christopher G. Wood*, Jose A. Karam*, Pheroze Tamboli*, Kanishka Sircar*, Priya Rao*, Paul G. Corn*, Nizar M. Tannir* and Eric Jonasch* *University of Texas MD Anderson Cancer Center, Houston, TX, USA, and †Ochsner Medical Center, New Orleans, LA, USA

Objectives To identify the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) with pancreatic metastases (PM) treated with either pazopanib or sunitinib and assess whether PM is an independent prognostic variable in the current therapeutic environment.

Patients and Methods A retrospective review of patients with mRCC in an outpatient clinic was carried out for the period January 2006 to November 2011. Patient characteristics, including demographics, laboratory data and outcomes, were analysed. Baseline characteristics were compared using chi-squared and t-tests and overall survival (OS) and cancer-specific survival (CSS) rates were estimated using Kaplan–Meier methods. Predictors of OS were analysed using Cox regression.

Results A total of 228 patients were reviewed, of whom 44 (19.3%) had PM and 184 (81.7%) had metastases to sites other than the pancreas. The distribution of baseline characteristics was equal in both groups, with the exception of a higher incidence of previous nephrectomy, diabetes and number of

metastatic sites in the PM group. Four patients had isolated PM, but the majority of patients (68%) with PM had at least three different organ sites of metastases, as compared with 29% in patients without PM (P < 0.01). The distribution of organ sites of metastases was similar, excluding the pancreas, in those with and those without PM (P > 0.05). The median OS was 39 months (95% confidence interval [CI] 24–57, hazard ratio 0.66, 95% CI 0.42–0.94; P = 0.02) for patients with PM, compared with 26 months (95% CI 21–31) for patients without PM (P < 0.01). CSS was 42 months (95% CI 30–57) in the PM group and 27 months (95% CI 22–33) in the control group (P = 0.05).

Conclusions Despite a higher number of affected organ sites in the PM cohort, mRCC behaviour in this cohort appears to be more indolent, as demonstrated by a higher median OS. These findings suggest that host or tumour features associated with PM may represent a less aggressive tumour phenotype.

Keywords carcinoma, renal cell, pancreatic metastases, overall survival, cancer specific survival, kidney, outcomes

The incidence of cancers arising from the kidney or the renal pelvis is ~65 000 new cases per year, accounting for 3–6% of all cancers in the USA, with RCC being the most common subtype [1–3]. The 5-year survival rate for patients with RCC confined to the kidney is ~95%; however, metastases are known to occur in ~30% of cases, which confers a 5-year survival rate ranging from 0 to 20% for patients with metastatic disease [3,4].

(MSKCC) risk criteria and the Heng criteria categorize patients into good, intermediate and poor risk groups [5,6]. Unfortunately, at this time there is limited insight into the molecular drivers of this clinical heterogeneity. Identifying unique disease subgroups with recognizable biological characteristics will provide an ideal starting point from which to perform comparative genomic, transcriptomic and proteomic assessments of both the tumour and the host, and will provide valuable information on the molecular drivers of tumour prognosis.

Validated algorithms that assess patient-specific clinical and laboratory characteristics to define prognosis for patients with metastatic RCC (mRCC) are currently used in clinical practice: the Memorial Sloan Kettering Cancer Center

In an effort to develop a biologically actionable categorization of patients with mRCC, we assessed patients with pancreatic metastases (PM) at our institution. Of the primary tumours that can metastasize to the pancreas, RCC is the most

Introduction

© 2015 The Authors BJU International © 2015 BJU International | doi:10.1111/bju.13185 Published by John Wiley & Sons Ltd. www.bjui.org

BJU Int 2016; 117: 761–765 wileyonlinelibrary.com

Kalra et al.

common, followed by lung and breast cancer [7–9]. PM are seen in a relatively small percentage of patients with mRCC, with published incidence ranging between 2 and 11% [4,10,11]. Approximately 22% of the PM cases are identified at the time of their primary tumour diagnosis [8]. Although PM are commonly associated with disseminated and advanced systemic disease for most cancers, nearly two-thirds of mRCC cases have been associated with an isolated spread to the pancreas [12,13]. RCC can behave in a variable manner, with up to 20% of cases having periods of slow growth or stability lasting for many years. The pancreas is frequently the only mRCC site and metastases have been reported to occur a long time after nephrectomy [14–16]. In the past decade, multiple targeted therapies received US Food and Drug Administration regulatory approval for mRCC. This evolving treatment armamentarium has improved patient outcomes, with lengthened progression-free survival and overall survival (OS). Currently, it is unknown how these agents have affected the clinical outcome of patients with PM. A few case series and retrospective studies, which were largely compiled in the pre-tyrosine kinase inhibitor era, have documented longer OS in patients with mRCC and PM. In the present study, we sought to identify the clinical outcomes of patients with mRCC and PM who were treated with either pazopanib or sunitinib, to assess whether PM is an independent prognostic variable in the current therapeutic environment, and to determine whether they are appropriate candidates for detailed molecular characterization to identify tumour and host-specific determinants of disease indolence and therapeutic response.

Patients and Methods After receiving institutional review board approval, we conducted a retrospective evaluation of patients diagnosed with mRCC at the University Of Texas MD Anderson Cancer Center between January 2006 and November 2011. Patients aged ≥18 years with clear-cell mRCC, who received first-line anti-angiogenic therapy with sunitinib or pazopanib, and who were available for adequate follow-up (at least one clinic visit at the MD Anderson Cancer Center within 3 months of treatment initiation), were included. Patients were stratified according to the presence or absence of PM at the time of presentation or during the course of their disease. Institutional electronic medical records were used to extract patient information. A formal review of radiological scans and reports was conducted for the identification of PM. Statistical Analysis Patient characteristics were summarized using medians and ranges for continuous variables and frequency and percentages for categorical variables. All statistical tests were two-sided and a P value ULN, n (%) 25 (57) LDH > 1.5 ULN, n (%) 18 (41) ANC > ULN, n (%) 11 (25) Diagnosis to treatment 21 (48) ULN Platelets > ULN LDH > 1.5 ULN ANC > ULN Diagnosis to treatment

Prognosis of patients with metastatic renal cell carcinoma and pancreatic metastases.

To identify the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) with pancreatic metastases (PM) treated with either pazopani...
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