Primary cutaneous melanoma. Optimized cutoff points of tumor thickness and importance of clark's level for prognostic classification

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Abstract
Background. Maximum tumor thickness and level of invasion are known to be the most important prognostic factors for patients with primary cutaneous melanoma. However, the classification of tumor thickness and the question of whether the combination of tumor thickness and level of invasion provides a better prognostic classification than tumor thickness alone are still matters of debate. The present study examined the relationship between tumor thickness and survival probability to define cutoff points of tumor thickness. Secondly, it investigated the prognostic value of the combination of tumor thickness and level of invasion as proposed in the current TNM classification system. Methods. A series of 5093 patients with invasive primary cutaneous melanoma followed from 1970 to 1988 at four University centers in Germany (Departments of Dermatology in Tübingen, Würzburg, Berlin-Steglitz, and at the Fachklinik) were analyzed by multivariate Cox models. Results. The relationship between tumor thickness and relative risk of death caused by melanoma was found to be almost linear to a tumor thickness of 6 mm. For tumors greater than 6 mm, no further marked increase in relative risk was observed. The stratification of tumor thickness with endpoints at 1,2, and 4 mm resulted in the best fit to the authors' data among all classifications with three endpoints, but differences were only slight. By multivariate analysis, the combination of tumor thickness and level of invasion as proposed by the current TNM classification were found to be prognostically less significant than tumor thickness alone. The prognostic influence of level of invasion was proved statistically only for tumor thickness less than or equal to 1 mm. Conclusions. The proposed stratification of tumor thickness with cutoff points at 1, 2, and 4 mm was supported by multivariate statistical analysis. The analysis of the current TNM staging system indicates the precedence of tumor thickness for the staging of patients with primary cutaneous melanoma in the case of discordance between tumor thickness and level of invasion.