Routine follow-up scanning of patients with lymphoma: who, when, how, and why?

In this issue of Leukemia and Lymphoma, Dr. El-Galaly and colleagues present the results of a single-center experience with positron emission tomography/computed tomography (PET/CT) in the routine post-treatment surveillance of patients with aggressive non-Hodgkin lymphoma (NHL) [1]. They looked exclusively at follow-up scans performed in patients with no suspicion of relapse, and showed that routine PET/CT detects a relapse prior to clinical symptoms in a small number of patients. Four relapses were discovered in 52 patients who were scanned 138 times for a median surveillance period of 18 months. More than 10% of all scans were false-positive, according to biopsies, repeat scans, and the clinical follow-up. Three of the four relapses found preclinically with PET/CT were also detectable with CT alone. In other words, the benefit of adding PET/CT to the routine surveillance regimen was the early detection of one single relapse. The authors have performed an interesting cost analysis, which, not surprisingly, shows a very high price for the detection of the very rare preclinical relapse detectable only by PET/CT.

The results of the present study confirm the findings of Zinzani and co-workers, who performed 1789 follow-up PET/CT scans in a prospectively studied cohort of 421 patients with lymphoma, the majority of whom had aggressive NHL or Hodgkin lymphoma (HL). PET/CT detected 34 relapses earlier than CT would have done. So in that study, it took 50 PET/CT scans to speed up the detection of one relapse [2]. A number of recent studies also show a high number of false-positive results, high costs, and limited added value when PET/CT is used routinely in the follow-up of patients with HL [3,4].

Chest X-ray and later CT scans were introduced into the routine surveillance of patients with lymphoma based on little evidence. Radford et al. studied 210 patients with HL and found that the vast majority of relapses were symptomatic, and the chest X-ray and blood tests only added minimal value [5]. Later, Guppy et al. followed a cohort of patients with diffuse large B-cell lymphoma and found the same thing: The large majority of relapsing patients had symptoms, and only 5.7% of relapses were detected in asymptomatic patients using surveillance CT scans [6]. Nevertheless, blood tests, X-ray, and CT are parts of the standard inventory for routine follow-up in lymphoma. Perhaps PET/CT is about to sneak in through the back door as well?

When considering the role of imaging in our routine surveillance strategies, two questions readily emerge. (1) What is the purpose of routine scanning? (2) Do patients benefit from having a relapse detected prior to the occurrence of symptoms and signs? While there are many possible answers to the first question: patient reassurance, monitoring of late effects, detection of second tumors, etc., early diagnosis of relapsing patients is probably the most important motivation for most clinicians. However, the honest answer to the second question is: we do not know. Although tumor burden is a prognostic factor, there is no evidence that relapsing patients with minimal, asymptomatic disease do better after salvage therapy than patients with low tumor burden and discrete symptoms.

In most patients with aggressive NHL and HL, it seems reasonable to stop performing routine CT after 2 years, when more than 90% of first relapses have occurred. For indolent lymphomas, there is little reason for routine follow-up imaging at all, considering that the indication for treatment of a preclinical relapse is far from absolute. There is no available evidence to support the use of PET/CT in the routine follow-up of patients with lymphoma. On the other hand, both CT and PET/CT may have relevance in certain high-risk patient groups. According to two recent studies, the risk of an early PET/CT-detected relapse is clearly increased in patients with a positive interim PET/CT [2] or a residual mass at the end of treatment [7]. El-Galaly and colleagues wisely suggest that it may be time for a more individualized and risk-adapted approach to follow-up schemes. Such an approach could relevantly include more systematic late monitoring of treatment-related morbidity, particularly in patients treated at a young age.

Large multicenter prospective studies are warranted to illuminate this subject, which is relevant to any lymphoma clinic. A desirable design would include a randomization of patients not otherwise on a clinical trial into a low-intensity versus a more traditional high-intensity surveillance arm. Provided there are sufficient numbers for stratification according to disease entities and risk groups, such a trial would perhaps answer some of the above questions which remain open.

Potential conflict of interest: A disclosure form provided by the author is available with the full text of this article at www.informahealthcare.com/lal.