Multiple myeloma is a type of cancer affecting plasma cells, a component of the immune system found primarily in the bone marrow. Staging is the process doctors use to classify the disease, which helps in determining a patient’s general outlook and creating an effective care plan. For multiple myeloma, the most current and comprehensive method is the Revised International Staging System (R-ISS).
It was introduced in 2015 to build upon a previous system by incorporating more advanced knowledge of the disease’s biology. This system gives clinicians a refined tool to assess the potential course of the disease by combining information from blood tests with genetic details from the cancer cells.
The R-ISS Staging Criteria
The Revised International Staging System (R-ISS) is built upon three specific indicators found in the blood and the genetic profile of the myeloma cells. Two of these blood markers, Beta-2 microglobulin (B2M) and lactate dehydrogenase (LDH), serve as measures of the tumor’s size and activity. B2M is a protein found on the surface of many cells, including myeloma cells, and higher levels in the blood suggest a larger amount of myeloma. A B2M level greater than 5.5 mg/L is associated with a less favorable prognosis.
LDH is an enzyme released into the bloodstream when cells are damaged or destroyed, so an elevated level can indicate a high tumor burden and rapid cell turnover. The third blood marker is serum albumin, a protein made by the liver. In myeloma, chemical signals from the cancer cells can suppress albumin production, so a lower level, specifically below 3.5 g/dL, points to more advanced disease and reflects the patient’s overall health.
Beyond blood tests, the R-ISS incorporates the analysis of cytogenetic abnormalities. These are specific changes or mutations within the chromosomes of the cancer cells. These abnormalities are detected through specialized laboratory tests performed on a bone marrow sample, most commonly a technique called fluorescence in situ hybridization (FISH).
Certain genetic changes are associated with a more aggressive form of myeloma and are categorized as “high-risk.” These include the deletion of a part of chromosome 17, known as del(17p), or the swapping of genetic material between two chromosomes, a process called translocation, such as t(4;14) or t(14;16). The absence of these specific high-risk markers categorizes the cytogenetics as “standard-risk,” providing insight into the cancer’s potential behavior.
Defining the R-ISS Stages
The criteria from blood tests and genetic analysis are combined to classify multiple myeloma into one of three stages. Each stage represents a distinct combination of these factors, providing a framework for understanding the disease’s status at diagnosis. This classification helps standardize how the disease is described among healthcare professionals.
R-ISS Stage I
Stage I represents the least aggressive form of the disease. A patient is classified as Stage I if their Beta-2 microglobulin (B2M) level is less than 3.5 mg/L and their serum albumin level is normal (≥3.5 g/dL). They must also have standard-risk cytogenetics and a normal lactate dehydrogenase (LDH) level.
R-ISS Stage III
Stage III indicates a more aggressive disease and is defined by a high B2M level (≥5.5 mg/L). This must also be accompanied by either the presence of high-risk cytogenetic abnormalities or an elevated LDH level in the blood.
R-ISS Stage II
R-ISS Stage II serves as the intermediate category. A patient is classified as Stage II if their disease characteristics do not fit the precise criteria for either Stage I or Stage III.
Prognostic Significance of Each Stage
Each R-ISS stage provides a general forecast, or prognosis, based on data from large populations of patients. It is important to understand that these are statistical averages and not a definitive prediction for any single person. An individual’s journey with myeloma is also influenced by their overall health and how their disease responds to therapy.
For individuals diagnosed with R-ISS Stage I, the general outlook is the most favorable. This classification suggests the myeloma is biologically less aggressive and the tumor burden is lower. Patients in this group, on average, have a longer period before the disease progresses and a longer overall survival.
R-ISS Stage III is associated with a less favorable prognosis. This stage signifies a high tumor burden combined with biological features, like high-risk genetics, that indicate a more aggressive form of myeloma. Consequently, the disease may progress more quickly, and survival expectations are statistically shorter than for Stages I and II.
R-ISS Stage II encompasses patients who fall between the definitions of Stage I and Stage III, and the prognosis for this group is intermediate. The outcomes for individuals in Stage II are better than those in Stage III but not as favorable as those in Stage I. The wide variability within this group means that individual outcomes can differ.
How Staging Influences Treatment Pathways
A patient’s R-ISS stage is a factor oncologists use to develop a personalized treatment strategy. The stage helps to quantify the risk associated with the myeloma, guiding decisions about the intensity and nature of the recommended therapy. This helps match the treatment plan to the biological behavior of the cancer.
For patients with a higher R-ISS stage, such as Stage III or some with Stage II, doctors might recommend a more intensive initial treatment regimen. This could involve using a combination of different therapeutic agents to control the disease more aggressively from the start. The goal is to achieve a deep and durable response, given the more challenging nature of the myeloma.
Staging also plays a part in determining eligibility for procedures like an autologous stem cell transplant. A transplant is a physically demanding procedure, and its suitability is based on a comprehensive evaluation of a patient’s overall health, age, and disease risk. A patient’s R-ISS stage is one element considered in this process.
The treatment landscape for multiple myeloma is constantly evolving, with new therapies emerging. While staging provides a foundational guide, the final treatment plan is highly individualized. Doctors consider the stage alongside a patient’s specific symptoms, kidney function, other medical conditions, and personal preferences.