Management of Localized-Stage Follicular Lymphoma: Changing the Paradigm?
Authors: Silvia Montoto
Journal: Journal of Clinical Oncology (2012)

For decades, the management of patients with follicular lymphoma (FL) has been guided by a series of premises that have been almost dogmatically accepted but which may need to be re-examined. One premise is that FL is an incurable disease, and thus, expectant management is an appropriate option in asymptomatic patients because immediate treatment does not prolong survival. The exception to this statement is the small proportion of patients with localized disease at diagnosis who can be cured with involved-field radiotherapy (IF-RT). The corollary to the latter statement is that it is not appropriate to manage these patients expectantly. Another classic axiom (the outcome of patients with FL has not improved over time) has been already contested with the publication of several articles that showed that the overall survival of patients diagnosed with FL in recent years is significantly longer than in the past. Has the time come for a paradigm shift in the management of patients with localized FL? In the article that accompanies this editorial, Friedberg et al challenge the widespread notion that the standard treatment for patients with localized FL is IF-RT. Both American (the National Comprehensive Cancer Network) and European (the European Society for Medical Oncology) guidelines recommend IF-RT as the preferred option for stage I and II FL. Despite this recommendation, fewer than one in four patients in the Friedberg et al study received local radiotherapy (RT). Moreover, the most commonly used management approach was observation. This discrepancy between guideline recommendations and real-world management is of concern. Guidelines are produced to ensure that patients are managed in a standardized fashion so that they receive the best care with the most-appropriate management for a given condition, regardless of where they are treated and who treats them. In contrast, Friedberg et al report a significant heterogeneity in the management of patients with localized FL. Does this discrepancy suggest that experts who write guidelines ignore crucial factors that patients and practicing physicians take into account when making a management decision? Alternatively, are the decisions taken by patients and doctors based on their own beliefs, regardless of what evidence-based guidelines recommend? In the LymphoCare study, approximately one third of patients were managed expectantly, one third of patients received rituximabbased treatment, and one quarter of patients were treated with the standard RT. Because of the nature of the study, the authors could not provide any information behind the reasons for patients and doctors to choose a specific treatment. As the reason for expectant management, one can speculate a nihilistic approach on the basis of the (pessimistic) belief that patients with FL cannot be cured; hence, watchful wait is bound to cause less harm than any treatment. On the otherextreme, theexcellentresultsachievedwith immunochemotherapy and the undoubted impact rituximab has made in the outcome of patients with FL might have led many (optimistic) patients and doctors to choose this option over the potentially curative RT. Rightly or wrongly, local RT is (was?) considered by most experts to be the standard treatment for localized FL precisely because of its potential curative effect. If the evidence for this statement is not strong enough, as discussed by Friedberg et al, there is even less evidence to support other approaches. In addition to the heterogeneous therapeutic approach to the management of patients with localized FL, the LymphoCare study also demonstrated considerable flexibility among treating physicians to follow the recommended standard staging investigations; in the study of Friedberg et al, fewer than one half of patients were appropriately staged (of note, the term “rigorously” that was used by the authors gives the impression of unnecessary and demanding investigations). It is important to emphasize that appropriately staged patients in this study had a better outcome than the remainder of patients, which underlines the importance of correct staging to be able to compare the results of different studies and for prognostic purposes and also in terms of the actual outcome of patients. This is especially relevant at a time when the management of patients with lymphoma has been revolutionized by the introduction of [F]fluorodeoxyglucose positron emission tomography (FDG-PET). The incurability of FL was the reason for the initial limited interest in the use of FDG-PET in the management of FL. However, a recent study has demonstrated a high predictive value of the response to initial therapy assessed by FDGPET in patients with advanced FL. If this result is confirmed in additional studies, and FDG-PET becomes the standard tool to assess the response at the end of treatment, a baseline FDG-PET will be essential to accurately assess the effect of therapy. In the study of Friedberg et al, the outcome of patients with stage I FL who had an FDG-PET as part of the initial staging did not differ from that of patients who had conventional imaging, which suggests, from the point of view of the authors, that FDG-PET does not offer any advantage in the management of patients with FL. The crucial question, however, is how the outcome of patients with stage 0-I FL by using conventional staging, but upstaged by FDG-PET, compares to that of patients with actual stage 0-I FL both by using conventional imaging and FDG-PET. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 27 SEPTEMBER 2