A recent study in Leukemia compared two staging systems that are commonly used to predict outcome in multiple myeloma patients: the Durie-Salmon staging system (DSS) and the International Staging System (ISS).

In patients who underwent autologous stem cell transplantation (ASCT), neither proved to be significantly more predictive than the other in outcome.

Staging systems are used by physicians in an attempt to predict outcome in myeloma patients at diagnosis. The traditionally used staging system, first published in 1975, is the DSS. The more recent ISS, published in 2005, has superseded the DSS because of its simplicity. It is the first alternative to the DSS to gain wide acceptance.

The two systems do not overlap in the parameters they measure. The DSS predicts tumor mass and estimates survival by using levels of immunoglobin proteins, hemoglobin and calcium concentrations, and number of bone lesions. The ISS, on the other hand, is based on levels of serum ß-2 microglobulin and albumin proteins.

The researchers analyzed the outcomes of 729 patients who underwent an autologous stem cell transplantation between 1995 and 2002.

The study showed agreement between the two staging systems to be 36 percent, a low correlation according to the study’s authors. For instance, among the 449 patients designated at diagnosis as DSS stage III, 29 percent were in ISS stage III, 41 percent in ISS stage II, and 30 percent in ISS stage I. Among the 170 patients designated as ISS Stage III, 78 percent were in DSS stage III, 20 percent in DSS stage II, and two percent in DSS stage I.

The differences in staging are apparent when looking at patient outcomes. The median progression-free survival for patients in DSS stages I, II, and III was 58, 31, and 24 months, respectively. For patients in ISS stages I, II, and III, progression-free survival was 33, 27, and 23 months, respectively.

The median overall survival for patients in DSS stages I, II, and III was 82, 68, and 50 months. For ISS stages I, II, and III, overall survival was 64, 68, 45 months, respectively.

The researchers then modeled the predictive value of both staging systems and analyzed the results using Brier scores, which measure inaccuracy, and R2 values, which measure how much variability in outcome is explained by the model. Lower Brier and higher R2 values indicate stronger predictive capability.

While both systems were somewhat predictive of progression-free survival and overall survival, the DSS was slightly superior in a formal statistical comparison. For example, overall survival for all patients at five years, or 60 months, was 52 percent. The DSS better predicted this value with an R2 value of 3.8 compared to an R2 value of 0.7 for the ISS.

However, neither staging system was strongly predictive of outcome. The authors acknowledge that for a biologically complex disease such as multiple myeloma it is unlikely that any one clinical staging system can fully accommodate all factors that affect outcome. They suggest the need for new staging system that would incorporate other predictive factors. These might include chromosomal studies, gene expression profiling (measurements of gene activity), or magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging studies.

For more information, see the article in Leukemia.