The role of anatomic and functional staging in myeloma: Description of Durie/Salmon plus staging system

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Abstract

Staging is the cornerstone of baseline myeloma evaluation. New imaging techniques such as magnetic resonance imaging (MRI), whole body FDG-PET scanning and whole body CT (combined with PET directly or by fusion) offer the opportunity to precisely stage patients by anatomic and functional techniques. The new Durie/Salmon PLUS staging system integrates these new imaging techniques into a new generation of anatomic and functional myeloma staging. It is possible to discriminate between the impact of tumour burden (myeloma cell mass) and other prognostic factors. This refined classification by stage and prognostic category is increasingly important in clinical trials. The value of clinical staging in patient management is emphasized both in discrimination of early disease status and clearer identification of poorer risk of Stage II and III disease. Wider use of newer imaging will undoubtedly enhance analysis of new trials incorporating novel agents.

Introduction

Multiple myeloma is a heterogeneous disease, which can present with or without overt symptomatology.1 The heterogeneity relates both to the intrinsic biology of the myeloma cells and bone marrow microenvironment as well as systemic host responses to the myeloma.2 The patient age, health status and the time of presentation to the healthcare system all impact outcome.

In an effort to standardize treatment approaches it is essential to characterize the disease as clearly as possible at the time of diagnosis. The Durie/Salmon myeloma staging system was introduced in 1975 to permit easy clinical staging which correlated with measured myeloma cell mass.3 This system has been widely used over the past 30 years. Despite the fact that classification based upon the number and extent of bone lesions found on X-ray is observer-dependent, the system has proved to be remarkably reliable.4, 5 Nonetheless, the availability of much more sensitive imaging techniques has required the integration of computed tomography, magnetic resonance imaging and FDG-PET scanning into routine anatomic and functional staging.6, 7, 8, 9 This has been accomplished by the development of the Durie/Salmon PLUS myeloma staging system (Table 1). The data supporting this new Durie/Salmon PLUS myeloma staging system and ways in which it can be implemented are discussed here in detail.

Section snippets

Limitations of anatomic staging using standard radiographs

Multiple myeloma can produce both localized lytic lesions and diffuse osteopenia evident on standard radiographs. Fracture of weakened areas is common. Early myeloma may not reveal observable changes on X-ray. Other imaging techniques show evidence of active myeloma in approximately 20% of patients with negative X-rays.8, 9 In addition, osteopenia may or may not be due to myeloma and can require further characterization. In some cases it may be difficult to determine if bone collapse or

Role of computed tomography (CT)

CT is the ideal tool for detection of early bone destruction.4, 6 Use of CT has enhanced the diagnosis of localized bone problems for many years. With the more recent availability of wide field and whole body techniques,7, 8 larger screening and assessment are possible (see Table 2). The combined use with FDG-PET is discussed below.9 Incorporation of FDG-PET helps overcome the difficulty in determining the age or activity status of lesions identified on CT. Since myeloma lesions frequently

The role of magnetic resonance imaging (MRI)

The use of MRI has added enormously to the ability to identify and monitor marrow infiltration with myeloma.10, 11, 12, 13 MRI is especially helpful for the evaluation of the axial skeleton. Infiltration at the site(s) of osteopenia or questionable lytic disease is diagnostically important. However, it is important to note that the MRI predominately reflects marrow infiltration, which may or may not be associated with bone destruction. Abnormal MRIs occur in patients with early smoldering

Whole body FDG-PET

This relatively new technique has several advantages for whole body screening.7, 9, 14, 15, 16 Firstly, it is possible to scan the whole body in a reasonable time frame. Since fluro-[F18]-deoxy glucose is taken up and retained by areas of active myeloma - one can assess both the location and activity of myeloma lesions. By considering the level of FDG uptake (SUV: Standardized Uptake Values, which take into account injected FDG dose and body weight) one can generally distinguish between active

Development of the Durie/Salmon PLUS staging system (Table 1)

The new system takes advantage of currently available imaging techniques. The Durie/Salmon PLUS system overcomes two major disadvantages of the original Durie/Salmon system.

  • 1.

    Better classification of early disease. Using CT-PET and/or MRI patients with definite active myeloma are distinguished from those with MGUS or smoldering disease. This is important for individual patients and to clarify protocol design.

  • 2.

    Discrimination among patients with stage II and III disease. Using the new imaging

The need for a multifaceted approach to staging and prognostic factor classification

Myeloma is heterogeneous at both the cellular and clinical levels.23, 24, 25 Therefore, no single system can encompass all patients. Table 4 shows a comparison of staging and prognostic factor systems. Some patients are hypo or non-secretory. For such patients high tumour burden is accompanied by low serum B2 microglobulin. ISS staging can therefore be misleading. Very indolent myeloma is not FDG avid and may not be detected with FDG-PET.9 However, such disease is usually detected by MRI26

Current and future role of imaging in myeloma

It is essential to integrate new imaging technology into myeloma staging in a systematic fashion. The Durie/Salmon PLUS myeloma staging system (Table 1) provides a reliable method for both staging and prognostic classification. The anatomic/functional staging is a direct approach, which serves as a basis for immediate clinical assessment and as a basis for clinical decision-making. A single focal lesion can be irradiated. Multiple lesions require a systemic approach. Both MRI and FDG-PET are

Conflict of interest statement

None declared.

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