Exploration of interactions between prognostic factors of stage I malignant melanoma

While many studies have sought prognostic factors of malignant melanoma using multivariate survival models, the interaction between predictors has been much less studied. We have studied data from 1,560 patients with stage I melanoma collected at the Cancer Registry of the Canton of Zurich over the period 1980-1990 and explored interactions between predictors by identifying two separate multivariate Cox models for men and women and investigating two-way interactions between predictors in each model. Considerable differences between models for man and women were observed. In particular, in women a pronounced interaction between 'histology' and 'Clark level' was identified. Without this interaction 'histology' and 'Clark level' are not significant but when the interaction term was included both predictors become significant. Thus, omission of an interaction term may preclude the recognition of main effects ('masking'). For female patients with nodular tumours prognosis is essentially independent of Clark level. In contrast, for female patients with non-nodular tumours, prognosis was found to be strongly dependent on Clark level. In the case of Clark level 2 prognosis was extremely good: no patient was observed to die from melanoma. We conclude that it may be worth considering interaction terms. With large enough sample sizes it may be preferable to stratify patients into subgroups and to identify separate models for each stratum instead of having to cope with interactions of higher order.