Abstract

Surveillance schedules in patients with cutaneous melanoma (CM) aim to detect metastatic spread in an early phase of development. Few studies investigated whether detection in an early phase is associated with prolonged survival and whether the observed longer survival times are a mere consequence of detection at an earlier time point (lead time bias). This is a long-term survival analysis of 1969 patients with stage I-III CM documented during 1996-1998 in the frame of a prospective surveillance study. Development of metastatic spread was detected in 112 patients during this period and classified as early phase or advanced phase based on tumor load and operability. The impact of lead time bias on differences in survival probabilities was examined using different statistical approaches. Of 59 patients with metastases detected in an early phase of development, 64.4% died of CM, of 43 patients with advanced phase metastases 86% died (P=0.013). The 10-year overall survival probability was 42.6% for early and 25.6% for advanced phase metastases (P=0.012). This comparison remained significant after adjustment for sojourn time. Multivariate analysis identified detection of early phase metastases (P=0.022) and stage at primary diagnosis (P<0.0001) as independent prognostic factors. In conclusion, this long-term follow-up study showed a factual gain in survival time for the detection of metastasis in an early phase of development beyond lead time bias. The classification of metastasis detected in early and advanced phase may be used in future studies aiming to improve melanoma surveillance.

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