Prognostic factors for mortality in nasopharyngeal cancer: accounting for time-dependence of relative risks.

BACKGROUND: Few studies have assessed the role of prognostic factors for mortality from nasopharyngeal cancer and even fewer used multivariable methods. Most of these studies relied on the Cox model without testing the proportional hazards assumption. METHODS: A cohort of 76 cases of nasopharyngeal cancer recorded in the Rhône, France, between 1980 and 1985, was followed until 1995. Proportional hazards assumption was tested for each putative prognostic factor. Two multivariable models were built using forward selection of prognostic factors: the Cox model and a flexible model in which variables not meeting the proportional hazards assumption were represented by a time-varying hazard ratio. RESULTS: Only Epstein Barr Virus Nuclear Antigen (EBNA) serology, a marker of infection by the Epstein-Barr virus, and tumoral extent were selected in the analysis based on the Cox model. In contrast, four prognostic factors were significant at alpha = 0.05 level in the flexible model: initial EBNA serology, tumoral histology, age and tumoral extent, the last two not verifying the proportional hazards assumption. The relative risk of age increases with duration of follow-up whereas the effect of tumoral extent changes in a non-monotonic pattern. CONCLUSION: We showed the importance of taking into account the non-proportionality of hazards which can influence results and yield new insights about the role of prognostic factors in nasopharyngeal cancer. Because of the small size of our cohort, our results have to be confirmed in an independent study.