Staging Multiple Myeloma: Understanding DS and R-ISS Classification Systems
When a patient is diagnosed with multiple myeloma, one of the first critical steps in clinical evaluation is determining the stage of the disease. Accurate staging helps guide treatment decisions, predict outcomes, and assess overall prognosis. Currently, two widely accepted staging systems are used in clinical practice: the Durie-Salmon (DS) Staging System and the Revised International Staging System (R-ISS). Each system uses different biomarkers and criteria to classify the progression of the disease into distinct phases.
The Durie-Salmon (DS) Staging System
The DS system categorizes multiple myeloma into three stages—Stage I, Stage II, and Stage III—based on a combination of laboratory values and imaging findings. This system focuses on tumor burden and its physiological impact on the body.
Stage I Characteristics
In Stage I, the disease is considered less advanced. Key indicators include hemoglobin levels greater than 100 g/L, indicating mild or no anemia. Patients at this stage typically show no significant bone destruction on imaging scans such as X-rays or CT scans. Additionally, serum calcium levels remain within normal limits—specifically below 2.65 mmol/L. The monoclonal (M) protein levels are also relatively low: IgG concentration is usually under 50 g/L, IgA under 30 g/L, and the 24-hour urinary light chain excretion is less than 4 grams. When all these favorable markers are present, the diagnosis falls under Stage I, suggesting a lower tumor mass and better prognosis.
Stage II – An Intermediate Phase
Stage II is not defined by strict numerical thresholds but rather serves as an intermediate category between Stage I and Stage III. Patients who do not meet the full criteria for either early-stage or advanced disease are classified here. This stage often includes individuals with moderate M-protein levels, slight bone involvement, or mild anemia that doesn't qualify for Stage III. Treatment plans for Stage II patients are tailored based on individual risk factors and may involve close monitoring or initiation of therapy depending on symptoms and disease activity.
Stage III – Advanced Disease Indicators
Stage III represents more aggressive disease progression. Diagnosis at this stage requires at least one of several key abnormalities. Hemoglobin drops significantly, falling below 85 g/L, indicating severe anemia. Imaging reveals extensive skeletal damage, with lytic lesions visible in three or more areas. Elevated calcium levels exceeding 2.65 mmol/L reflect increased bone resorption. Furthermore, M-protein levels rise substantially—IgG surpasses 70 g/L, IgA exceeds 50 g/L, and 24-hour urine light chains exceed 12 grams. The presence of any one of these markers qualifies the patient for Stage III classification, which correlates with higher tumor burden and generally poorer outcomes.
The Revised International Staging System (R-ISS)
While the DS system emphasizes tumor mass and organ dysfunction, the R-ISS offers a more modern and refined approach by integrating key biochemical markers and genetic risk profiles. It divides multiple myeloma into three stages—Stage I, II, and III—based primarily on two blood tests: serum albumin and beta-2 microglobulin (β2-M).
R-ISS Stage I – Favorable Prognosis
Patients classified under R-ISS Stage I typically have a better outlook. This stage is defined by a serum albumin level greater than 35 g/L and a β2-microglobulin level below 3.5 mg/L. These values suggest preserved organ function and limited tumor spread. Individuals in this group often respond well to standard therapies and may experience longer remission periods.
R-ISS Stage II – Intermediate Risk Group
Stage II encompasses patients whose lab results fall between those of Stage I and Stage III. This intermediate category includes various combinations of albumin and β2-microglobulin levels that don't meet the strict cutoffs for either low or high risk. Because this group is heterogeneous, additional factors such as age, comorbidities, and cytogenetic abnormalities are often considered when planning treatment strategies.
R-ISS Stage III – High-Risk Classification
An R-ISS Stage III designation occurs when the β2-microglobulin level exceeds 5.5 mg/L, indicating widespread disease and likely impaired kidney function. This stage is associated with high tumor load and adverse genetic features, leading to a more aggressive clinical course. Patients in this category generally require intensive treatment approaches, including novel agents, stem cell transplantation, or enrollment in clinical trials targeting high-risk myeloma.
Both the DS and R-ISS systems play vital roles in managing multiple myeloma. While the DS model provides insight into tumor burden and physical manifestations, the R-ISS enhances prognostic accuracy by incorporating molecular and laboratory data. Clinicians often use both systems together to develop personalized care plans, monitor response to therapy, and adjust interventions over time. Early and accurate staging remains essential for optimizing survival and improving quality of life in patients battling this complex hematologic malignancy.