Multiple Myeloma Staging: Understanding DS, ISS, and R-ISS Systems for Better Prognosis

Multiple myeloma, a type of blood cancer affecting plasma cells, is classified using several staging systems that help doctors assess disease severity, predict outcomes, and tailor treatment plans. Over the decades, advancements in medical understanding and diagnostic technology have led to the development of three primary staging models: the Durie-Salmon (DS) system, the International Staging System (ISS), and the revised version known as the Revised International Staging System (R-ISS). Each offers unique insights into tumor burden, patient prognosis, and survival expectations.

Durie-Salmon (DS) Staging System: Assessing Tumor Burden

The Durie-Salmon staging system was first introduced in the 1960s and remains one of the earliest frameworks used to evaluate multiple myeloma. This model primarily focuses on tumor mass or disease burden within the body, relying heavily on clinical and laboratory markers collected at diagnosis.

In the DS system, hemoglobin levels play a crucial role in determining the stage. A hemoglobin level below 85 g/L typically indicates Stage III, reflecting significant anemia caused by extensive bone marrow involvement. Conversely, patients with hemoglobin above 100 g/L are classified as Stage I, suggesting lower tumor activity. Those falling between these values are categorized as Stage II.

Besides hematologic parameters, the DS system also considers the extent of bone destruction, assessed through skeletal surveys or imaging techniques like X-rays. Widespread lytic lesions correlate with higher stages, reinforcing the link between structural damage and overall tumor load. While this system provides valuable insight into physical disease burden, it has limitations in predicting long-term survival due to its lack of molecular and genetic data.

International Staging System (ISS): Focusing on Prognosis

Introduced around 2005, the International Staging System (ISS) marked a shift from assessing tumor volume to predicting patient outcomes. Unlike the DS model, the ISS relies solely on two key serum biomarkers: beta-2 microglobulin (β2-M) and serum albumin.

Elevated β2-M levels indicate increased tumor activity and impaired kidney function, while low albumin reflects systemic inflammation and poor nutritional status—both linked to worse prognosis. In the ISS framework:

• Stage I: β2-M < 3.5 mg/L and albumin ≥ 35 g/L
• Stage II: Values that don't meet Stage I or III criteria
• Stage III: β2-M > 5.5 mg/L

Patients in Stage I generally experience more favorable outcomes, with a median survival exceeding five years. In contrast, those diagnosed at Stage III face a significantly shorter median survival—often less than two years—highlighting the system's strength in forecasting disease progression and mortality risk.

Revised International Staging System (R-ISS): Integrating Genetic Risk Factors

As genomic research advanced, clinicians recognized the need to refine prognostic tools beyond biochemical markers alone. The Revised International Staging System (R-ISS), introduced in 2015, builds upon the ISS by incorporating critical cytogenetic abnormalities and lactate dehydrogenase (LDH) levels—factors proven to influence survival.

Key Components of the R-ISS Model

The R-ISS integrates three essential elements for improved accuracy:

1. ISS stage (based on β2-M and albumin)
2. High-risk chromosomal abnormalities detected via fluorescence in situ hybridization (FISH), including del(17p), t(4;14), and t(14;16)
3. Elevated LDH levels, which signal aggressive disease and tissue turnover

Patients without high-risk genetic features and normal LDH fall into R-ISS Stage I, associated with the best prognosis. Those exhibiting any high-risk marker or elevated LDH are staged accordingly, with R-ISS Stage III representing the highest risk group and poorest survival outlook.

This modernized approach allows oncologists to stratify patients more precisely, enabling personalized therapy decisions such as early consideration of stem cell transplantation or enrollment in clinical trials targeting specific mutations.

Why Staging Matters in Multiple Myeloma Management

Accurate staging is vital not only for estimating life expectancy but also for guiding therapeutic strategies and monitoring response over time. While the DS system laid the foundation by linking clinical findings to tumor burden, the ISS and especially the R-ISS offer superior predictive power by integrating biology-driven metrics.

Today, most healthcare providers use the R-ISS as the gold standard due to its comprehensive nature and alignment with current treatment paradigms. However, all three systems continue to contribute to a fuller understanding of disease dynamics, particularly when used together in complex cases.

For patients and caregivers, understanding these staging systems can empower informed discussions with medical teams, improve awareness of disease trajectory, and support proactive decision-making throughout the treatment journey.