Improved Survival for Patients With Follicular Lymphoma
Authors: T. Andrew Lister
Journal: Journal of Clinical Oncology (2005)

It is claimed by Swenson et al in this issue that survival for patients with follicular lymphoma improved during the last quarter of the last century. Despite the fact that the improvement is modest, this observation is intriguing, particularly considering similar results from both a single center and a cooperative group presented during this past year. The findings should be considered in light of our previous knowledge of the natural history of this disease and the impact on it of both irradiation and chemotherapy. There is a relative paucity of information about the natural history of follicular lymphoma because a large proportion of patients, even in the earliest series, received at least irradiation at some point. However, it is undoubtedly a relatively indolent condition in which spontaneous regression may occur and in which, in a proportion of patients, progression may be slow. Transformation to a more aggressive histologic type may occur and usually carries a poor prognosis. The clinical course of the disease (ie, the natural history modified by therapy) in the 20th century was largely that of a remitting recurring disease, with death usually resulting from the illness after several years. Responsiveness to therapy was the rule rather than the exception, with responders living longer than nonresponders but cure being rare. The median survival, which was reported in large series from major centers during the time when irradiation was almost the only treatment, was 5 years. Subsequently, with the demonstration of the potential role of chlorambucil, chemotherapy became the treatment of choice for advanced disease at the initial presentation, with irradiation reserved for local or locoregional disease. In the setting of trials of initial therapy designed to test the curability of the disease (which failed) with alkylating agent– based combinations with or without anthracyclines and re-treatment at recurrence (usually with chemotherapy), it was established that the median survival time was approximately 10 years, with the average patient having had three episodes of therapy at approximately 3-year intervals. Thus, it might be argued that between the mid-1960s and the mid-1980s, chemotherapy had led to a doubling of the median survival time, even if resulting in few cures. In their article, Swenson et al present the outcome for several thousand patients with follicular lymphoma reported from nine population-based Surveillance, Epidemiology, and End Results cancer registries between 1978 and 1999. Attractively, the results are not only presented in terms of overall survival of cohorts of patients in sequential time periods, but they are also presented in terms of reduction in the risk of dying relative to the normal population. Detailed analysis of a subset of patients for whom staging was considered adequate suggests that the improvement occurs mainly in patients presenting with advanced disease. What were the differences in the management of follicular lymphoma between the 1970s and the 1990s that could account for an improvement, albeit of less than a year, in survival? One possibility that was not considered is that, with increasing awareness of the curability of some types of lymphoma, painless adenopathy, which might otherwise have been ignored, might have been brought to the attention of the physician and, thus, the diagnosis made sooner, giving a lead time effect. If, as is likely, this is not the case and the improvement is real, what is new? Without doubt, newer chemotherapy regimens, including drugs such as fludarabine, are effective when alkylating agent– based treatments fail. Newer regimens have resulted in high complete remission rates with longer progression-free survival from first-line therapy and have also attained molecular remissions, which may confer a survival advantage. Myeloablative consolidation therapy of second remission induces long responses and, in a small randomized trial, resulted in an improvement in overall survival. Interferon alone induces remissions and, in a meta-analysis, has been JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 22 AUGUST 1 2005