BETHESDA, MD — The National Comprehensive Cancer Network (NCCN) Guidelines continue to recommend conducting a skeletal survey or whole-body radiography as the first step in identifying osteolytic bone lesions and distinguishing between smoldering multiple myeloma (SMM) and multiple myeloma (MM). The International Myeloma Working Group recommends whole body computerized tomography (CT) or positron emission tomography (PET)/CT scan as the first imaging choice. Who’s right?

A team of federal researchers including scientists from the Walter Reed National Military Medical Center and the National Cancer Institute, both in Bethesda, MD, and the U.S. Food and Drug Administration in Silver Spring, MD, contend that skeletal surveys do more harm than good. That conclusion is based on a study they presented in a poster at the 2020 American Society of Clinical Oncologists Annual Meeting held May 29-31.1

The researchers noted that the false-negative rate of skeletal surveys is known to be quite high, in the range of 30% to 70%. That high rate underlies the NCCN recommendation to conduct more sensitive screening such as F-FDG-PET/CT(PET/CT), magnetic resonance imaging (MRI), or low dose CT, if a skeletal scan is negative.

To better understand the value of the skeletal survey with the availability of more precise imaging, the team sought to determine the frequency of false positives associated with the older technology.

They examined records of 144 patients sequentially referred from the community to the National Institutes of Health Myeloma Program; all patients had a presumed diagnosis of SMM between April 2010 and January 2020. The 76 patients included in the final analysis had both skeletal survey and PET/CT performed within 30 days.

The team used findings on the PET/CT scan as the reference test, with the skeletal survey and PET/CT scan having consistent results in 64 (84.2%) of the patients.

Among the 12 with conflicting results, the skeletal survey missed lesions in three (false negatives) and produced falsely positive results in nine cases. The study found the skeletal survey had a sensitivity of just 57.1% and a specificity of 86.9%.

Because smoldering multiple myeloma patients typically have a low burden of disease, ruling out bone disease requires a highly sensitive imaging modality, the researchers said. Skeletal survey, with its low sensitivity, does not rise to the challenge.

Further, they argued, the low specificity of the survey overestimates the disease. Patients run the risk of unnecessary treatment with implications for both physical and financial toxicity.

The researchers recommended that if skeletal surveys are used as a first-line imaging modality, positive findings should be discussed with a radiologist and physicians should consider confirmatory testing just as they do with negative results. Having to conduct a second imaging study, however, effectively negates any advantage provided by the survey’s relatively low cost and widespread availability.

  1. Hill EM, Dew A, Morrison C, Choyke PL, Mena E, Lindenberg L, Kazandjian DG. “Diagnostic performance of skeletal survey versus 18F-FDG-PET/CT for detecting lytic lesions in smoldering multiple myeloma.” Abstract 8532. Poster 432. 2020 ASCO Virtual Scientific Program. May 29-31, 2020.