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      Barriers to pre-treatment genomic characterization of the small renal mass

      editorial
      , ,
      Oncotarget
      Impact Journals LLC
      RCC, genomics, biopsy, kidney cancer, active surveillance

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          Abstract

          Small renal mass clinical challenge The widespread availability of cross-sectional imaging has led to a rise in incidentally detected small renal masses (≤ 4 cm). Stage 1 tumors are now found in 60-70% of all new kidney cancer diagnoses [1, 2]. Most small renal tumors will remain indolent after detection and it has been consistently shown that the vast majority are not destined for metastatic spread. With a slow growth rate and low potential for stage progression in the small renal mass, the role of active surveillance for these tumors has expanded. The median age of diagnosis for kidney cancer is 64 years and many of these patients have significant competitive comorbidities. Surgery may expose these patients to possible unnecessary treatment or overtreatment for benign and indolent tumors [3]. As such, the American Urologic Association recommends active surveillance for small renal masses detected in the elderly and infirm patients. Although active surveillance is an adequate option for certain patient populations, it is not a guarantee that treatment will be avoided indefinitely as patients may undergo delayed treatment due to tumor growth kinetics or even patient anxiety. As it remains, there are no universally accepted guidelines for determining the need for upfront or delayed intervention in the small renal mass. Thus, there remains a need to better identify patients at highest risk in hopes of avoiding unnecessary over-treatment and maximizing survival. Issues with molecular profiling in kidney cancer Renal cell carcinoma represents a genetically diverse population of cancers. Despite our knowledge of adverse pathologic features which portend to worse survival in the small renal mass such as nuclear grade [4], histology alone may not fully characterize the risk of progression and metastasis. With the introduction of clinical cancer genetics in the realm of kidney cancer, there has been an opportunity to correlate altered genomic events and expression patterns to progression and survival after surgical resection. For patients with small renal masses, molecular profiling with a percutaneous biopsy represents a modality that can be potentially utilized for stratifying disease risk prior to treatment. A perceived obstacle to this is the concern for tumor heterogeneity. As opposed to a large renal mass where multiple biopsies can be easily obtained for adequate characterization of subclonal events, the small renal mass may only be able to accommodate a single biopsy and there is concern that clinically meaningful driver alterations may go undetected given tumor heterogeneity. A homogenous tumor profile To address the issue of genomic heterogeneity in the small renal mass (SRMs) Ueno et al. compared 23 small (< 4 cm) and 24 large (> 7 cm) renal masses [5]. The study is the largest of its type to date (n = 47) and analyzed three ≥ 1 cm apart designated regions from each tumor. Genomic heterogeneity was assessed through 3 methods: DNA copy number variation (CNV), and mRNA gene expression by 2 transcriptomic RNA classifiers: the clear-cell A and B system and the CCP Score. From CNV, small renal masses were found to have significantly less subclonal events when compared to large tumors. On gene expression profiling, 4.7% (1/21) vs. 23.8% (5/21) had mixed clear-cell A and B classifications in the SRMs and large masses, respectively. While median CCP scores did not differ between the SRMs and large masses, there was an increased variance found for large masses. Implications to management The findings demonstrate that SRMs had limited copy number variation and transcriptomic heterogeneity. The homogeneous expression profile would theoretically strengthen the argument that an enhanced renal mass biopsy, a standard biopsy plus incorporation of genomic profiling, may be useful for patients with a small renal mass as the limitations of tumor heterogeneity may not be as pronounced as they are in larger tumors. The incorporation of such a tool clinically has the potential to shift the diagnostic paradigm for patients with SRMs and help decide who may benefit most from early intervention. While this approach is now technically feasible, high cost and the lack of clinical utility studies may prevent widespread adoption. Our center is currently developing assays to lower the cost of assessment and evaluating the clinical utility in the management of the SRM.

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          Renal cell cancer stage migration: analysis of the National Cancer Data Base.

          Evidence exists to suggest a pattern of increasing early diagnosis of renal cell carcinoma (RCC). The aim of the study was to analyze patterns of disease presentation and outcome of RCC by AJCC stage using data from the National Cancer Data Base (NCDB) over a 12-year period. The NCDB was queried for adults diagnosed between 1993 and 2004 presenting with ICD-O-2 of 3 renal cell tumors arising in the kidney. Cases were classified by demographics, 2002 AJCC stage (6th edition), and histology. The Cochran-Armitage Test for Trend was used to determine statistical significance of trends over time. Cox regression multivariate analysis was used to evaluate the impact of stage and histology on relative survival. SPSS 14.0 was used for analyses. Between 1993 and 2004 a total of 205,963 patients from the NCDB fit our case definition of RCC. Comparisons between 1993 and 2004 data show an increase in stage I disease and decrease in stage II, III, and IV disease (P < or = .001). The size of stage I tumors also decreased from a mean of 4.1 cm in 1993 to 3.6 cm in 2003. In multivariate analysis, stage, but not histology, predicted relative survival. A 3.3% increase in survival was found for patients diagnosed in 1998 compared with patients diagnosed in 1993. A greater proportion of newly diagnosed patients with RCC currently present with stage I disease compared with earlier years. Stage predicts relative survival for patients with kidney cancer. More recently diagnosed patients have improved relative survival. (Copyright) 2008 American Cancer Society.
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            Author and article information

            Journal
            Oncotarget
            Oncotarget
            Oncotarget
            ImpactJ
            Oncotarget
            Impact Journals LLC
            1949-2553
            1 March 2019
            1 March 2019
            : 10
            : 18
            : 1667-1668
            Affiliations
            Department of Urology, Institute of Urologic Oncology (IUO), David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
            Author notes
            Correspondence to: Brian Shuch, bshuch@ 123456m ednet.ucla.com
            Article
            26756
            10.18632/oncotarget.26756
            6422204
            d3e40a6c-ae48-4b0c-ae46-a961e8c6db09
            Copyright: © 2019 Syed et al.

            This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

            History
            : 11 November 2018
            : 23 February 2019
            Categories
            Editorial

            Oncology & Radiotherapy
            rcc,genomics,biopsy,kidney cancer,active surveillance
            Oncology & Radiotherapy
            rcc, genomics, biopsy, kidney cancer, active surveillance

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