ORLANDO, Fla. — A large, multicenter, randomized trial presented at the American Society of Clinical Oncology's annual meeting here this week suggests that the current practice of monitoring cancer antigen 125 serum levels to predict women most at risk of relapse of ovarian cancer may be unnecessary.
The study, led by researchers at the UK's Mount Vernon Cancer Centre and the Netherlands' Erasmus MC University Medical Center, found no evidence that CA-125 monitoring made a difference in the overall survival of ovarian cancer patients who were "immediately" treated with chemotherapy based on CA-125 levels and those whose treatment was "delayed" until symptoms of recurrence showed.
"There is no survival benefit from early treatment based on a raised serum marker level alone, and therefore no value in the routine measurement of C-125 in the follow-up of ovarian cancer patients," the authors concluded in the abstract.
Separately at the meeting, in a discussion of this abstract, Beth Karlan, chair of gynecologic oncology at Cedars-Sinai Medical Center and editor-in-chief of Gynecologic Oncology, lauded the trial results for potentially affecting changes to the standard of care in the treatment of ovarian cancer.
While oncologists should not entirely stop monitoring CA-125 in their early detection and treatment strategies for ovarian cancer patients, Karlan noted that the study results do suggest more limited monitoring of CA-125 in women with asymptomatic ovarian cancer.
Given the rising cost of healthcare, Karlan expressed that the study's findings could help oncologists avoid unnecessary CA-125 monitoring. Furthermore, Karlan urged for the "strategic use" of funding under the American Recovery and Reinvestment Act to continue discoveries in personalized therapies and advance early detection strategies in cancer treatment.
CA-125 is a protein encoded by the MUC16 gene. Monitoring of CA-125 has become standard practice in oncology as a prognostic indicator of ovarian cancer recurrence.
In the study, researchers registered 1,442 women with a median age of 61 years whose ovarian cancer had gone into complete remission after receiving first-line, platinum-based chemotherapy. The participants were recruited from 59 sites in 10 countries between 1996 and 2005. The study randomized 527 patients whose CA-125 levels exceeded twice the upper limit of normal patients. All women's CA-125 levels were measured every three months but patients and investigators were blinded to the results.
Of 527 randomized patients, 264 received "immediate" chemotherapy based on CA-125 levels, while treatment for 263 was "delayed" until symptoms of cancer recurrence appeared. Patients in both arms were treated based on standard local treatment practices. Second-line chemotherapy started at a median of five months earlier in the "immediate" arm.
The study was designed to detect a 10 percent improvement in two-year overall survival in the "immediate" treatment arm with at least 85 percent power and 5 percent significance level. The primary outcome measure was overall survival.
Once the number of targeted deaths was reached, randomization was closed on March 31, 2008. As a result, 915 patients were not randomized due to: no CA-125 rise and no relapse in 48 percent of patients; relapse with or without CA-125 rise in 30 percent of patients; death in 6 percent of patients; withdrawal from the study by 14 percent of patients; or for other reasons cited by 2 percent of patients.
With a median follow-up of 49 months from randomization and a total of 351 deaths, there was no evidence of a difference in overall survival between the immediate and delayed arms, the researchers reported.
There are few marketed diagnostics for the early detection and treatment of ovarian cancer. However, there are efforts ongoing at various research organizations to identify other protein markers that can be used in conjunction with CA-125 to improve ovarian cancer monitoring.
According to the Laboratory Corporation of America, its OvaSure multiplex immunoassay interrogates six protein biomarkers, including leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, and CA-125. However, LabCorp had to stop marketing its OvaSure test after it received a warning letter from the US Food and Drug Administration last year that the test was not validated in the treatment population [see PGx Reporter 09-03-2008].