Originally published as JCO Early Release 10.1200/JCO.2003.01.094 on October 14 2003

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vergouwe, Y. Articles by Habbema, J. D. F. Search for Related Content PubMed PubMed Citation Articles by Vergouwe, Y. Articles by Habbema, J. D. F. Social Bookmarking                            What's this?

Predictors of Occult Metastasis in Clinical Stage I Nonseminoma: A Systematic Review

Yvonne Vergouwe, Ewout W. Steyerberg, Marinus J.C. Eijkemans, Peter Albers, J. Dik F. Habbema

From the Center for Clinical Decision Sciences, Department of Public Health, Erasmus MC, Rotterdam, The Netherlands; and the Department of Urology, Bonn University, Bonn, Germany.

Address reprint requests to Yvonne Vergouwe, PhD, Center for Clinical Decision Sciences, Department of Public Health, Ee20-33, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, The Netherlands; e-mail: y.vergouwe{at}erasmusmc.nl.

Purpose: Patients with clinical stage I nonseminomatous testicular germ cell tumor should ideally receive adjuvant therapy only when they are at high risk for occult metastasis. We aimed to quantify the importance of predictors for occult metastasis by performing a systematic review of the relevant literature. In addition, we reviewed published multivariable models and risk-adapted treatment policies.

Patients and Methods: We identified 23 publications between 1979 and 2001, reporting a total of 2,587 patients. Twenty-nine percent of the patients (759 of 2,587 patients) had occult metastases, which was diagnosed either at retroperitoneal lymph node dissection (n = 193) or during follow-up (n = 566). Odds ratios (OR) were pooled using meta-analysis techniques.

Results: The presence of vascular invasion of the primary tumor cells had the strongest effect (OR, 5.2; 95% CI, 4.0 to 6.8). Immunohistochemical staining of the primary tumor cells with the MIB-1 monoclonal antibody showing proliferative activity was a promising predictor (OR, 4.7; 95% CI, 2.0 to 11). Intermediate effects were found for embryonal carcinoma in the primary tumor (OR, 2.9; 95% CI, 2.0 to 4.4) and a high pathologic stage of the tumor (OR, 2.6; 95% CI, 1.8 to 3.8). Size of the primary tumor and age of the patient had weaker though also statistically significant associations with occult metastasis. Until now, multivariable models often included vascular invasion and embryonal carcinoma with one or two weaker predictors. None of the published risk-adapted treatment policies included MIB-1 staining.

Conclusion: Several strong predictors for occult metastasis were identified. A risk-adapted treatment policy should be developed that incorporates all relevant predictors so that adjuvant therapy is targeted better to those with occult metastases.

Supported by the Netherlands Organization for Scientific Research (Y.V.) and a fellowship from the Royal Netherlands Academy of Arts and Sciences (E.W.).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. Kollmannsberger, C. Moore, K. N. Chi, N. Murray, S. Daneshmand, M. Gleave, B. Hayes-Lattin, and C.R. Nichols Non-risk-adapted surveillance for patients with stage I nonseminomatous testicular germ-cell tumors: diminishing treatment-related morbidity while maintaining efficacy Ann. Onc., October 29, 2009; (2009) mdp473v1. [Abstract] [Full Text] [PDF]

				T. Tandstad, O. Dahl, G. Cohn-Cedermark, E. Cavallin-Stahl, U. Stierner, A. Solberg, C. Langberg, R. M. Bremnes, A. Laurell, H. Wijkstrom, et al. Risk-Adapted Treatment in Clinical Stage I Nonseminomatous Germ Cell Testicular Cancer: The SWENOTECA Management Program J. Clin. Oncol., May 1, 2009; 27(13): 2122 - 2128. [Abstract] [Full Text] [PDF]

				C. J. Pezaro, G. Mallesara, and G. C. Toner Late Relapsing Stage I Nonseminoma J. Clin. Oncol., December 1, 2008; 26(34): 5647 - 5648. [Full Text] [PDF]

				C. M. Sturgeon, M. J. Duffy, U.-H. Stenman, H. Lilja, N. Brunner, D. W. Chan, R. Babaian, R. C. Bast Jr., B. Dowell, F. J. Esteva, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Testicular, Prostate, Colorectal, Breast, and Ovarian Cancers Clin. Chem., December 1, 2008; 54(12): e11 - e79. [Abstract] [Full Text] [PDF]

				P. Albers, R. Siener, S. Krege, H.-U. Schmelz, K.-P. Dieckmann, A. Heidenreich, P. Kwasny, M. Pechoel, J. Lehmann, S. Kliesch, et al. Randomized Phase III Trial Comparing Retroperitoneal Lymph Node Dissection With One Course of Bleomycin and Etoposide Plus Cisplatin Chemotherapy in the Adjuvant Treatment of Clinical Stage I Nonseminomatous Testicular Germ Cell Tumors: AUO Trial AH 01/94 by the German Testicular Cancer Study Group J. Clin. Oncol., June 20, 2008; 26(18): 2966 - 2972. [Abstract] [Full Text] [PDF]

				J. Sheinfeld and R. J. Motzer Stage I Testicular Cancer Management and Necessity for Surgical Expertise J. Clin. Oncol., June 20, 2008; 26(18): 2934 - 2936. [Full Text] [PDF]

				G. J. Rustin, G. M. Mead, S. P. Stenning, P. A. Vasey, N. Aass, R. A. Huddart, M. P. Sokal, J. K. Joffe, S. J. Harland, and S. J. Kirk Randomized Trial of Two or Five Computed Tomography Scans in the Surveillance of Patients With Stage I Nonseminomatous Germ Cell Tumors of the Testis: Medical Research Council Trial TE08, ISRCTN56475197--The National Cancer Research Institute Testis Cancer Clinical Studies Group J. Clin. Oncol., April 10, 2007; 25(11): 1310 - 1315. [Abstract] [Full Text] [PDF]

				R. de Wit and K. Fizazi Controversies in the Management of Clinical Stage I Testis Cancer J. Clin. Oncol., December 10, 2006; 24(35): 5482 - 5492. [Abstract] [Full Text] [PDF]

				J. Oldenburg, J. M. Martin, and S. D. Fossa Late Relapses of Germ Cell Malignancies: Incidence, Management, and Prognosis J. Clin. Oncol., December 10, 2006; 24(35): 5503 - 5511. [Abstract] [Full Text] [PDF]

				P. Maroto, X. G. del Muro, J. Aparicio, L. Paz-Ares, J. A. Arranz, J. Guma, J. Terrassa, J. Barnadas, J. Dorta, and J. R. Germa-Lluch Multicentre risk-adapted management for stage I non-seminomatous germ cell tumours Ann. Onc., December 1, 2005; 16(12): 1915 - 1920. [Abstract] [Full Text] [PDF]

				D. Raghavan New Prognostic Factors for Stage I Testicular Cancer: But Will They Make It to Broadway? J. Clin. Oncol., November 15, 2003; 21(22): 4075 - 4076. [Full Text] [PDF]