While it is an inexpensive, low-risk, and convenient diagnostic test for myeloma bone disease, skeletal survey has limitations, which have prompted the use of more sophisticated imaging, including CT, MRI and PET scans in certain clinical situations. Skeletal survey can miss early bony lesions and potentially underestimate the extent of myeloma. It has been shown that spine X-rays may not be able to detect an area of involvement due to myeloma unless more than half of the spongy bone component within each vertebra has been damaged. Moreover, it is difficult to assess the response to treatment with plain X-rays since the areas of bone destruction are unlikely to look substantially different after successful therapy.
MRI and low-dose CT scans have greater sensitivity in the diagnosis of myeloma bone disease. Low-dose CT scan is more sensitive in detecting spine lesions, and has the ability to detect areas of involvement outside the bone marrow. In nearly half of the patients with normal skeletal survey, an MRI could identify more areas of involvement. While an isolated spine MRI is superior to skeletal survey for disease detection, about 10% of patients with myeloma have involvement of the skeleton outside the spine and pelvis (i.e., in limbs, ribs, etc.). Therefore, a whole body (instead of axial) MRI is a superior imaging modality for defining the extent of myeloma. A spine MRI is particularly indicated if spinal cord or nerve root compression is suspected.
Screening by skeletal survey or low-dose CT scan is necessary for every myeloma patient. Low-dose CT scan is more sensitive in detecting spine lesions, and has the ability to detect areas of involvement outside the marrow. In contrast, a skeletal survey has greater ability to detect lesions in arms and legs as well as the skull.
An FDG PET scan can survey almost the entire body in one session and has the advantage of differentiating areas of active disease involvement from inactive (dormant) disease. Additionally, PET scans can detect areas of involvement outside the bone (extramedullary disease). A PET scan result can therefore impact management decisions. A major downside, however, is the limited spatial resolution of PET scans. Lesions of sizes below a centimeter may be difficult to pick up.
Combining CT scan with PET (i.e. PET-CT), however, can overcome the issue of spatial resolution. The CT part of this imaging technique allows for anatomic correlation (spatial orientation) of the area of increased activity on the PET scan. Additionally, the detection rate of bone lesions increases by performing a CT scan. The sensitivity of PET scan in catching an area of myelomatous involvement can be as high as 85%.
Although this technique increases the detection rate of lesions, the specificity is compromised. In other words, the chances of inadvertently missing the areas of involvement (lesions) are less, but unfortunately areas may be incorrectly identified as being actively involved by myeloma (false positive) as other conditions, particularly those associated with inflammation or infection, can show similar findings of increased tracer (FDG) uptake on the PET scan. A PET scan just tells us that an area is “hot”. Therefore, for “hot areas” overlying a bone, it is important to look at the CT images as well to identify any areas of bone destruction.
Needless to state that a PET/CT has been found to be superior to plain X-rays in detection of myeloma lesions!
But, because it exposes patients to more radiation, is more expensive and its costs may not be reimbursed by insurance providers, the question that needs to be addressed is whether it is required for evaluation of all myeloma patients.
In an Italian study, a PET-CT scan was able to detect areas of involvement in nearly half of the patients with newly diagnosed myeloma in whom X-rays showed either no lesions or underestimated the myeloma burden. However, in nearly one-third of the patients in that study, the PET/CT scan also failed to detect areas of involvement in the spine and pelvis that were detected by MRI. In fact, as a sole imaging modality, PET-CT could miss small lytic lesions and diffuse spine involvement compared to MRI.
On the other hand, approximately a third of patients in the Italian study had lesions that were outside the view of MRI, and were therefore detected by PET/CT scan, but not MRI. Moreover, a PET-CT scan, as opposed to an MRI, can be performed in patients with pacemakers and defibrillators.
Doctors are still learning to integrate these modalities into their practice. For example, MRI findings in smoldering myeloma patients (who by definition have no detectable areas of bone destruction on X-rays) can be predictive of outcomes as they provide additional information about the rate of progression to active myeloma. Smoldering myeloma patients with normal MRIs have a lower rate of progression to active, symptomatic disease. If more than 1 focal lesion is noted on MRI of smoldering myeloma patient, the chances of progression to active myeloma are greater. If the pattern of marrow involvement on MRI is similar to that seen in monoclonal gammopathy of undetermined significance (MGUS) patients, the chances to progressing into symptomatic multiple myeloma are lower. Importantly, areas with bone marrow abnormalities detected on MRI may not necessarily suggest increased threat to bone destruction. However, closer monitoring may be required due to higher risk of progression to active disease.
Although large studies delineating the role of PET scan in smoldering myeloma patients are unavailable, my colleagues and I have at times used PET findings to guide our management decision regarding treatment versus observation.
FDG PET-CT and MRI, when used at diagnosis, also help predict patient outcomes. A particularly hot/intensely avid area (measured as SUV of over 4.2), more than 3 focal areas of involvement, and extramedullary disease on PET scan are findings associated with worse outcomes.
Unlike MRI, a PET-CT is useful in evaluating response after treatment, particularly in the post- transplant setting. Persistently active lesions post initial (induction) treatment or after auto-stem cell transplantation are associated with unfavorable outcomes, as suggested by two large studies. The Arkansas Group has reported on the prognostic significance of early PET scan performed on day 7 of induction (initial pre-transplant) therapy. Hopefully, in the future, studies would help guide physicians in modifying therapies early on in the disease course in a non-responding patient with multiple persistent lesions on the PET scan. Information pertaining to response assessment with PET in the transplant ineligible population is scant. Another advantage of PET-CT scan, besides detecting extramedullary disease, is its potential to assess low tumor burden (minimal residual disease) after therapy.
I hope the reader is beginning to get an idea that these tools can be considered as complementary, as no single imaging modality is perfect in managing patients with multiple myeloma, and combining these tools may be appropriate, if clinically indicated. I state ‘clinically indicated’, as these are expensive tools, and will not necessarily help change our treatment approach in every patient with active myeloma.
Outside of clinical trials with mandatory scans, I typically order a PET-CT scan or an alternative sensitive imaging technique in circumstances where I feel that additional information may assist me in formulating a management plan for my patient. Some of the clinical scenarios would be:
- Managing a patient with normal plain X-rays, but with symptomatic areas (for example, presence of a lump or localized swelling or bone pain)..
- To follow a patient with non-secretory myeloma.
- As part of a diagnostic work-up of solitary plasmacytoma, in addition to spine MRI. In one study, treatment of almost 30% of the patients was directly impacted by identification of additional lesions on their PET scans.
- Evaluating a patient labeled as having ‘smoldering multiple myeloma’, but the clinical suspicion for active myeloma is high (a whole body MRI would be a good option as well).
- Discordance between the bone marrow biopsy findings and laboratory studies, where the marrow indicates a low myeloma burden, but other tests, including monoclonal protein studies, are suggestive of substantial disease. Sometimes, the biopsy sample may not be representative of the actual tumor burden due to the patchy distribution of abnormal myeloma cells, and can therefore underestimate the actual myeloma burden.
Meanwhile, physicians should exercise judgment in ordering a battery of studies, and patients should question the need for additional imaging recommended by their providers.
to that?