To Surveil or Not to Surveil
Authors: James O. Armitage, Julie M. Vose
Journal: Journal of Clinical Oncology (2015)

It is logical that for a patient with an aggressive malignancy, for whom potentially curative therapy is available after relapse, early diagnosis of relapse identified by surveillance imaging might be beneficial. Diffuse large B-cell lymphoma fits these criteria. We have known for many years that patients who experience relapse from complete remission can be cured with autologous bone marrow transplantation. However, it has been difficult to prove the benefit of surveillance imaging in this clinical setting. A study carried out by physicians at the Mayo Clinic, the University of Iowa, and the Centre Lyon Berard in Lyon, France, tried to estimate the value of postremission surveillance imaging for patients with diffuse large B-cell lymphoma in a retrospective analysis. They studied a large number of patients who achieved complete remission with a regimen containing an anthracycline and rituximab. Twenty percent of the patients experienced relapse during the period of observation, but most of the relapses were identified at a time other than a scheduled follow-up visit. Surveillance imaging uniquely detected relapse in only 1.6% of patients. There was no difference in survival in patients whose relapse was detected at a routine follow-up visit versus those detected because of the onset of new symptoms. The authors concluded that these data did not support the use of routine surveillance imaging in diffuse large B-cell lymphoma. A study from Korea evaluated routine imaging during remission in an attempt to identify early relapses. The authors found that routine imaging led to unsatisfactorily high false-positive imaging results and did not improve treatment outcome. A study from Australia found that the positive predictive value of positron emission tomography (PET)/computed tomography (CT) imaging in remission was 80% in patients with a high International Prognostic Index score, and the authors concluded that routine surveillance imaging with PET/CT scans might be reasonable in this subgroup of patients. A study by Petrausch et al from Zurich, Switzerland, found that the positive predictive value of surveillance PET scans in patients age 60 years with symptoms of relapse was sufficiently high enough to recommended surveillance imaging in this group. However, if the patient had symptoms of relapse, one might argue that this was not surveillance imaging. Physicians from Denmark found that patients who underwent routine surveillance imaging were more likely to be diagnosed with a low disease burden and have better overall survival in a retrospective analysis. It is interesting that these are the same authors whose patients were included in the article by El-Galaly et al that accompanies this editorial. It is not surprising that it has been difficult to identify a survival benefit for surveillance imaging in patients with diffuse large B-cell lymphoma. Surveillance imaging is screening for early relapse. The mathematics used to analyze screening tests take into account the sensitivity and specificity of the test being used and the prevalence of the condition for which the screening is being performed in the population being screened. Our data in Nebraska suggest that the chances of relapse for a patient with diffuse large B-cell lymphoma being detected on any particular follow-up visit are approximately one in 40 to 50. Applying these data to the formula for the positive predictive value of screening tests suggests that, given the published sensitivity and specificity of CT scans (PET scans are more sensitive but less specific), the chance that an abnormal scan would represent lymphoma would be approximately 20%. This means that 80% of patients with a positive screening CT scan would be unnecessarily exposed to biopsies and the documented anxiety associated with the procedure. Because treatment for recurrent lymphoma without histologic confirmation of diagnosis would be medically inappropriate, this would mean that all patients would be exposed to the complications associated with the biopsy necessary to make the diagnosis. The situation is even less positive, because many patients are diagnosed in between scheduled visits as a result of new symptoms. Presumably, with rapidly growing lymphoma, even those patients with relapsed disease detected by surveillance imaging would have become symptomatic within a short period of time. The best way to solve this dilemma would be a randomized trial where patients with diffuse large B-cell lymphoma felt to be at sufficiently high risk of relapse to potentially justify surveillance imaging would be randomly assigned to routine follow-up or surveillance imaging to determine whether there is survival benefit associated with surveillance imaging. It is unlikely that any such study will be completed. However, the next best approach might be the situation reported by El-Galaly et al published in Journal of Clinical Oncology. The authors took advantage of the situation where two similar countries (Denmark and Sweden) had opposite policies for surveillance imaging for patients with diffuse large B-cell lymphoma. Both employed similar follow-up visit intervals and studies, except for the fact that routine surveillance imaging was not performed in Sweden and was performed in Denmark. In Denmark, CT scans were obtained every 6 months for the first 2 years of follow-up. The authors were able to identify factors that correlated to likelihood of relapse (eg, age 60 years and elevated lactate dehydrogenase), but routine surveillance imaging had no impact on outcome for all patients or for any International Prognostic Index–specific subgroup. The authors suggested JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 34 DECEMBER 1 2015