Breslow thickness of 1.00mm or more or of Clark level IV or V with any Breslow thickness were eligible for inclusion, but patients with intermediate thickness melanoma (1.20 to 3.50mm) were the primary study group. Two thousand and one patients were registered and enrollment closed in 2002. The randomisation process assigned 60% of patients to the wide excision and sentinel node biopsy group and 40% of patients to the wide excision and nodal observation group. In the intermediate thickness group there were 1347 patients with 814 in the sentinel node biopsy group and 533 in the nodal observation group. There was just over 4% cross over from each arm with 35 patients in the sentinel node biopsy group actually undergoing observation and 22 patients in the nodal observation group actually having sentinel node biopsy. Sentinel node biopsy was shown to accurately detect occult nodal disease in 96% of cases and sentinel node status was confirmed as the most powerful predictor of survival in the study population. The 10-year melanoma-specific survival rate (mean +/- standard error) for the biopsy group was 81.4+/-1.5% versus 78.3+/-2.0% for the observation group. This difference was not statistically significant. One of the problems with this trial was that the ideal comparison groups (sentinel node positive patients versus patients who develop nodal recurrence in the observation group) could not be identified prior to the point of randomisation and so statistical comparison of melanoma-specific survival for these two groups could be affected by bias. In order to compare these two groups and to account for potential bias the authors employed a statistical method called latent subgroup analysis and found that the melanoma-specific survival time for sentinel node positive patients in the sentinel node biopsy group was double that of patients who developed nodal recurrence in the nodal observation group. This finding was the case only in the intermediate thickness melanoma group. In the thick melanoma group (>3.50mm) there was no significant difference in survival and in the thin melanoma group (<1.20mm) there were relatively few cases with nodal disease and so statistical analysis was not reported. THE SIGNIFICANCE OF NODAL METASTASIS BEYOND SENTINEL NODES
Breslow thickness of 1.00mm or more or of Clark level IV or V with any Breslow thickness were eligible for inclusion, but patients with intermediate thickness melanoma (1.20 to 3.50mm) were the primary study group. Two thousand and one patients were registered and enrollment closed in 2002. The randomisation process assigned 60% of patients to the wide excision and sentinel node biopsy group and 40% of patients to the wide excision and nodal observation group. In the intermediate thickness group there were 1347 patients with 814 in the sentinel node biopsy group and 533 in the nodal observation group. There was just over 4% cross over from each arm with 35 patients in the sentinel node biopsy group actually undergoing observation and 22 patients in the nodal observation group actually having sentinel node biopsy. Sentinel node biopsy was shown to accurately detect occult nodal disease in 96% of cases and sentinel node status was confirmed as the most powerful predictor of survival in the study population. The 10-year melanoma-specific survival rate (mean +/- standard error) for the biopsy group was 81.4+/-1.5% versus 78.3+/-2.0% for the observation group. This difference was not statistically significant. One of the problems with this trial was that the ideal comparison groups (sentinel node positive patients versus patients who develop nodal recurrence in the observation group) could not be identified prior to the point of randomisation and so statistical comparison of melanoma-specific survival for these two groups could be affected by bias. In order to compare these two groups and to account for potential bias the authors employed a statistical method called latent subgroup analysis and found that the melanoma-specific survival time for sentinel node positive patients in the sentinel node biopsy group was double that of patients who developed nodal recurrence in the nodal observation group. This finding was the case only in the intermediate thickness melanoma group. In the thick melanoma group (>3.50mm) there was no significant difference in survival and in the thin melanoma group (<1.20mm) there were relatively few cases with nodal disease and so statistical analysis was not reported. THE SIGNIFICANCE OF NODAL METASTASIS BEYOND SENTINEL NODES