Urological Survey Urological Oncology: Adrenal, Renal, Ureteral and Retroperitoneal Tumors Re: ClearCode34: A Prognostic Risk Predictor for Localized Clear Cell Renal Cell Carcinoma S. A. Brooks, A. R. Brannon, J. S. Parker, J. C. Fisher, O. Sen, M. W. Kattan, A. A. Hakimi, J. J. Hsieh, T. K. Choueiri, P. Tamboli, J. K. Maranchie, P. Hinds, C. R. Miller, M. E. Nielsen and W. K. Rathmell UNC Lineberger Comprehensive Cancer Center, Department of Medicine, Division of Hematology and Oncology, and Departments of Pathology, Urology, Epidemiology and Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, New York, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, Department of Medical Oncology and Kidney Cancer Center, Dana-Farber Cancer Institute, Boston, Massachusetts, Department of Pathology, MD Anderson Cancer Center, Houston, Texas, and Department of Urologic Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania Eur Urol 2014; 66: 77e84.
Abstract available at http://jurology.com/ Editorial Comment: Following a long period of testing multiple independent biomarkers with limited applications in clinical practice, in renal cell carcinoma (RCC), as in other cancers, research moves toward developing genetic signatures based on a combination of biomarkers that can add predictive oncologic value to the pathological and clinical factors currently in use. Based on previous work that defined 2 prognostic subgroups, the authors devised a signature biomarker for clear cell (cc) RCC based on 34 biomarkers, named ClearCode34. Validation of the predictive ability of the biomarker model followed in 2 nonmetastatic ccRCC external cohorts. Finally, an integrated model including ClearCode34, tumor staging and Fuhrman grade was developed and tested in the external cohort. This integrated model could predict relapse, outperformed the UCLA Integrated Staging System and Mayo Clinic Stage, Size, Grade and Necrosis score to predict death from ccRCC, and had added value over the 2 clinicohistopathological integrated systems. Although not the first to be described, the ClearCode34 biological model was methodologically developed and properly validated. This integrated model still requires external validation. However, there is little doubt that so-called personalized medicine is the future, and that biomarker models will add prognostic value to the gross clinical and histopathological features. Costs and resources should not be an issue when weighed against followup adaptation and possibility of early therapeutic interventions. M. Pilar Laguna, MD, PhD
Suggested Reading Adamy A, Chong KT, Chade D et al: Clinical characteristics and outcomes of patients with recurrence 5 years after nephrectomy for localized renal cell carcinoma. J Urol 2011; 185: 433. Chen D, Gassenmaier M, Maruschke M et al: Expression and prognostic significance of a comprehensive epithelial-mesenchymal transition gene set in renal cell carcinoma. J Urol 2014; 191: 479. Yang XJ, Sugimura J, Schafernak KT et al: Classification of renal neoplasms based on molecular signatures. J Urol 2006; 175: 2302.
0022-5347/15/1931-0071/0 THE JOURNAL OF UROLOGY® © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2014.10.015 Vol. 193, 71-74, January 2015 Printed in U.S.A.
www.jurology.com
j
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ADRENAL, RENAL, URETERAL AND RETROPERITONEAL TUMORS
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Kim CM, Vocke C, Torres-Cabala C et al: Expression of hypoxia inducible factor-1alpha and 2alpha in genetically distinct early renal cortical tumors. J Urol 2006; 175: 1908. White NM, Bao TT, Grigull J et al: miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation. J Urol 2011; 186: 1077. Lam JS, Shvarts O, Leppert JT et al: Renal cell carcinoma 2005: new frontiers in staging, prognostication and targeted molecular therapy. J Urol 2005; 173: 1853.
Re: Hereditary-Like Urothelial Carcinomas of the Upper Urinary Tract Benefit More from Adjuvant Cisplatin-Based Chemotherapy after Radical Nephroureterectomy than do Sporadic Tumours , A. Ouzzane, C. Hollande, P. Colin, T. de La Motte Rouge, F. Audenet, D. R. Yates, V. Phe S. Droupy, A. Ruffion, A. de La Taille, L. Guy, O. Cussenot, F. Rozet, E. Xylinas, M. Zerbib, ^t; French Collaborative National J. P. Spano, D. Khayat, M. O. Bitker and M. Roupre Working-Group on UTUC Academic Department of Oncology, University Paris VI, Paris, France BJU Int 2014; 113: 574e580.
Abstract available at http://jurology.com/ Editorial Comment: The urological community is by now aware of the close relationship between hereditary nonpolyposis colorectal cancer (HNPCC, previously Lynch syndrome) and upper tract urothelial carcinoma (UTUC). Overall the syndrome should be suspected not only in the presence of colorectal carcinoma, but also with earlier age at onset of UTUC and when first or second degree relatives have a history of HNPCC related cancers. Applying these clinical criteria as a selection tool, the authors retrospectively assessed oncologic outcomes in a population of patients undergoing cisplatin based chemotherapy after nephroureterectomy for UTUC. They found a high incidence of hereditary-like UTUCs (31.3%). Overall survival and cancer specific survival were significantly higher in the hereditary-like group compared to the nonhereditary-like group, although disease-free survival was similar in both groups. The small sample of the cohort precludes any definitive conclusions. Because no genetic testing (MSI or MSH2) was performed, the high incidence of a hereditary component in this study may be merely an overestimation of the selection tool or the result of population selection, with young patients being more likely to undergo chemotherapy than older ones. The strength of the study is in directing the urological community to increase awareness of the fact that the prevalence of hereditary UTUC may be greater than suspected. As the hereditary-like group may have a better prognosis than the nonhereditary-like group, efforts regarding genetic identification will not be lost, and at the same time the hypothesis that these cases could be sensitive to other types of chemotherapy than cisplatin based, as occurs with HNPCC, deserves future investigation. M. Pilar Laguna, MD, PhD
Suggested Reading Crockett DG, Wagner DG, Holm€ang S et al: Upper urinary tract carcinoma in Lynch syndrome cases. J Urol 2011; 185: 1627. Lynch HT, Ens JA and Lynch JF: The Lynch syndrome II and urological malignancies. J Urol 1990; 143: 24.
Abstract available at http://jurology.com/ Editorial Comment: Following a long period of testing multiple independent biomarkers with limited applications in clinical practice, in renal cell carcinoma (RCC), as in other cancers, research moves toward developing genetic signatures based on a combination of biomarkers that can add predictive oncologic value to the pathological and clinical factors currently in use. Based on previous work that defined 2 prognostic subgroups, the authors devised a signature biomarker for clear cell (cc) RCC based on 34 biomarkers, named ClearCode34. Validation of the predictive ability of the biomarker model followed in 2 nonmetastatic ccRCC external cohorts. Finally, an integrated model including ClearCode34, tumor staging and Fuhrman grade was developed and tested in the external cohort. This integrated model could predict relapse, outperformed the UCLA Integrated Staging System and Mayo Clinic Stage, Size, Grade and Necrosis score to predict death from ccRCC, and had added value over the 2 clinicohistopathological integrated systems. Although not the first to be described, the ClearCode34 biological model was methodologically developed and properly validated. This integrated model still requires external validation. However, there is little doubt that so-called personalized medicine is the future, and that biomarker models will add prognostic value to the gross clinical and histopathological features. Costs and resources should not be an issue when weighed against followup adaptation and possibility of early therapeutic interventions. M. Pilar Laguna, MD, PhD
Suggested Reading Adamy A, Chong KT, Chade D et al: Clinical characteristics and outcomes of patients with recurrence 5 years after nephrectomy for localized renal cell carcinoma. J Urol 2011; 185: 433. Chen D, Gassenmaier M, Maruschke M et al: Expression and prognostic significance of a comprehensive epithelial-mesenchymal transition gene set in renal cell carcinoma. J Urol 2014; 191: 479. Yang XJ, Sugimura J, Schafernak KT et al: Classification of renal neoplasms based on molecular signatures. J Urol 2006; 175: 2302.
0022-5347/15/1931-0071/0 THE JOURNAL OF UROLOGY® © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2014.10.015 Vol. 193, 71-74, January 2015 Printed in U.S.A.
www.jurology.com
j
71
ADRENAL, RENAL, URETERAL AND RETROPERITONEAL TUMORS
72
Kim CM, Vocke C, Torres-Cabala C et al: Expression of hypoxia inducible factor-1alpha and 2alpha in genetically distinct early renal cortical tumors. J Urol 2006; 175: 1908. White NM, Bao TT, Grigull J et al: miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation. J Urol 2011; 186: 1077. Lam JS, Shvarts O, Leppert JT et al: Renal cell carcinoma 2005: new frontiers in staging, prognostication and targeted molecular therapy. J Urol 2005; 173: 1853.
Re: Hereditary-Like Urothelial Carcinomas of the Upper Urinary Tract Benefit More from Adjuvant Cisplatin-Based Chemotherapy after Radical Nephroureterectomy than do Sporadic Tumours , A. Ouzzane, C. Hollande, P. Colin, T. de La Motte Rouge, F. Audenet, D. R. Yates, V. Phe S. Droupy, A. Ruffion, A. de La Taille, L. Guy, O. Cussenot, F. Rozet, E. Xylinas, M. Zerbib, ^t; French Collaborative National J. P. Spano, D. Khayat, M. O. Bitker and M. Roupre Working-Group on UTUC Academic Department of Oncology, University Paris VI, Paris, France BJU Int 2014; 113: 574e580.
Abstract available at http://jurology.com/ Editorial Comment: The urological community is by now aware of the close relationship between hereditary nonpolyposis colorectal cancer (HNPCC, previously Lynch syndrome) and upper tract urothelial carcinoma (UTUC). Overall the syndrome should be suspected not only in the presence of colorectal carcinoma, but also with earlier age at onset of UTUC and when first or second degree relatives have a history of HNPCC related cancers. Applying these clinical criteria as a selection tool, the authors retrospectively assessed oncologic outcomes in a population of patients undergoing cisplatin based chemotherapy after nephroureterectomy for UTUC. They found a high incidence of hereditary-like UTUCs (31.3%). Overall survival and cancer specific survival were significantly higher in the hereditary-like group compared to the nonhereditary-like group, although disease-free survival was similar in both groups. The small sample of the cohort precludes any definitive conclusions. Because no genetic testing (MSI or MSH2) was performed, the high incidence of a hereditary component in this study may be merely an overestimation of the selection tool or the result of population selection, with young patients being more likely to undergo chemotherapy than older ones. The strength of the study is in directing the urological community to increase awareness of the fact that the prevalence of hereditary UTUC may be greater than suspected. As the hereditary-like group may have a better prognosis than the nonhereditary-like group, efforts regarding genetic identification will not be lost, and at the same time the hypothesis that these cases could be sensitive to other types of chemotherapy than cisplatin based, as occurs with HNPCC, deserves future investigation. M. Pilar Laguna, MD, PhD
Suggested Reading Crockett DG, Wagner DG, Holm€ang S et al: Upper urinary tract carcinoma in Lynch syndrome cases. J Urol 2011; 185: 1627. Lynch HT, Ens JA and Lynch JF: The Lynch syndrome II and urological malignancies. J Urol 1990; 143: 24.
