Can we now agree to use the same definition to measure response according to CA-125?

Abstract

Oncologists use measurement of response as an indicator that the therapy they are administering is effective. This information can then be used to decide whether to continue, change, or stop therapy and may also be used as a surrogate end point in a clinical trial. The Response Evaluation Criteria in Solid Tumors (RECIST) 1 have been accepted as the standard methodology for measuring response. Many patients with ovarian cancer do not have measurable disease, so response cannot often be measured using RECIST criteria. Oncologists have therefore considered using the tumor marker CA-125 as an alternative method for monitoring the treatment of patients with ovarian carcinoma. Serum levels of CA-125 are elevated in more than 90% of patients with advanced epithelial ovarian cancer. 2,3 Several different definitions of response based on CA-125 have been proposed, which has led to a variation in the response rate to a particular agent from 10% to 62% in the same group of patients, depending on which definition is used. 4 The Gynecologic Cancer Intergroup (GCIG) consists of representatives from the major gynecologic cancer trial groups around the world. After considerable debate—and after several versions—the GCIG has proposed a precise but simple definition for response according to CA-125, based on a 50% reduction in CA-125 levels that is confirmed and maintained for at least 28 days. 5 This definition, with examples demonstrating its implementation, is posted on the GCIG Web site (http://ctep.info.nih.gov/ resources/gcig/index.html). There are difficulties in validating a new response definition based on a tumor marker, as some patients are only assessable by scans and some are only assessable by the tumor marker. In some patients, scans might classify the response differently from the tumor marker. If a patient is classified as having stable disease by scans but as a responder according to the tumor marker, which is correct? The simplest method used to validate definitions of response based on CA-125 has been to compare response rates according to CA-125 with response rates according to standard criteria and calculate the proportion of patients in whom the CA-125 prediction agrees or differs with the response determined by standard criteria. 6 The accuracy of the definition for response according to CA-125 has also been determined by examining how accurate the CA125‐ defined response was in predicting the activity of drugs in phase II trials, compared with response rates obtained by standard criteria. 7