When and how to perform surveillance imaging in patients with lymphoma, and is it worth it?

Why, when and how to perform surveillance imaging in lymphoma patients has been a debated topic for a long time. More than 25 years after the introduction of computed tomography (CT) and more than 10 years after the introduction of positron emission tomography (PET)/CT, there is still no substantial evidence supporting the widespread use of routine imaging in patients who achieve a good remission after therapy. Even though routine scans detect some relapses prior to the development of symptoms, it has not yet been demonstrated that detecting the relapse at a subclinical stage will in fact improve the eventual outcome [1].

In this issue of Leukemia and Lymphoma, Abel and colleagues report their findings gathered from a multi-institutional survey of the patterns and significance of surveillance imaging of patients in remission after treatment for diffuse large B-cell lymphoma (DLBCL) [2]. With the participation and cooperation of seven different academic lymphoma treatment centers, they identified a cohort of 845 patients treated between 2000 and 2008 who were all in remission for at least 3 months post-therapy and had a minimum of least 2 years of follow-up. After the exclusion of 220 patients who had died, developed a second cancer or were lost to follow-up during the first 2 years, they were finally left with a cohort of 625 patients. In the analysis of imaging frequency, the authors focused on the use of surveillance imaging during the first 2 years post-treatment. Twenty-two patients who relapsed less than 6 months after therapy were excluded from this analysis in order to avoid the counting of frequent re-imaging of patients in questionable remission after therapy. Since the authors had also excluded patients with an unsatisfactory remission status and patients who died and/or relapsed very early after therapy, the remainder must be regarded as a “good-risk“ group of patients. Nevertheless, among the remaining 603 patients, they found that the median number of imaging studies was 2.5 per year per patient. There was wide variation between centers, with mean numbers of imaging studies per patient ranging from 0.5 to 3.5 per year. This supports the suspicion that surveillance imaging strategies are founded on local preferences and habits rather than evidence-based medicine.

Just over 50% of the patients had PET or PET/CT performed at some stage during the first 2 years of follow-up [2]. Fifty of the 625 patients relapsed during a median follow-up of 5 years, and no more than a quarter of those relapses were identified by routine imaging of asymptomatic patients. This implies that more than 120 scans had in fact been performed to identify one patient with asymptomatic relapse.

In 2003, Guppy et al. published results from a cohort of patients with DLBCL and found that the large majority of relapsing patients had symptoms, while only 5.7% of relapses were detected in asymptomatic patients using surveillance CT scans [3]. Zinzani and co-workers performed 1789 follow-up PET/CT scans in a prospectively studied cohort of 421 patients with lymphoma, the majority of whom had aggressive non-Hodgkin lymphoma or Hodgkin lymphoma. PET/CT detected some relapses earlier than CT would have done, but in that study it also took 50–100 PET/CT scans to speed up the detection of one relapse [4]. More recent studies also show an unexpectedly 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 both Hodgkin and non-Hodgkin lymphomas [5,6].

Routine imaging is associated with high costs, and the imaging studies may be a source of patient anxiety as well as patient reassurance, and may also result in considerable radiation exposure over the long term. Furthermore, the frequent false positive results, particularly with PET/CT, result in a large number of unnecessary and potentially harmful diagnostic procedures being performed in the wake of results received [7]. Indeed there is little evidence to support the use of routine follow-up imaging in patients with DLBCL who achieve a complete remission after first-line therapy. El-Galaly and colleagues suggested that it may be time for a more individualized and risk-adapted approach to follow-up schemes [6]. Such an approach could include more systematic late monitoring of treatment-related morbidity, particularly in patients treated at a young age. Large multicenter prospective studies are warranted to shed more light on this subject. A currently ongoing trial randomizes patients to low-intensity surveillance imaging versus more traditional high-intensity surveillance imaging after completion of adjuvant chemotherapy for colon cancer [8]. Those patients have a risk of relapse comparable to patients with DLBCL in remission after chemotherapy. A similar study of patients with DLBCL and Hodgkin lymphoma is warranted in the near future.

Potential conflict of interest:

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