SAN ANTONIO — Elevated cancer antigen 125 levels measured after surgery but before chemotherapy are an independent prognostic indicator of recurrence and worse survival in women with high-risk, early-stage epithelial ovarian cancer, according to results of a Gynecologic Oncology Group study.
Moreover, the highest recurrence and worst 5-year survival rates were seen in a subgroup of women whose high postsurgery CA 125 levels persisted after they started treatment, perhaps suggesting a poor response to chemotherapy, Dr. Joshua P. Kesterson reported at the annual meeting of the Society of Gynecologic Oncologists.
Serum CA 125 levels are used to assess response to therapy and to detect recurrences, mainly in advanced epithelial ovarian cancer. Some studies have looked at CA 125 levels before chemotherapy in stage I disease. The current study, in 350 women, is the first to look at CA 125 levels after surgery but before chemotherapy, said Dr. Kesterson of a cancer research and treatment center in Buffalo, N.Y.
Looking at the primary end points, Dr. Kesterson reported 5-year recurrence-free survival rates of 86% in women who had normal CA 125 levels after surgery, and 75% in those with high levels at that point. The 5-year overall survival rate was likewise higher when women had normal CA 125 levels before chemotherapy, compared with those who had high levels (88% vs. 82%).
Information for the current analysis came from a phase III clinical trial (GOG-157) that compared three vs. six cycles of adjuvant chemotherapy with paclitaxel and carboplatin in surgically staged women with stage IA/B grade 3 or stage IC or stage II epithelial ovarian cancer. Investigators deemed CA 125 levels that were 35 U/mL or lower to be normal.
Preclinical data were available on 350 of 427 eligible patients: 110 women (31%) who had a normal CA 125 level before chemotherapy, and 240 (69%) with elevated CA 125 at that point. The median level was 65 U/mL after primary surgery.
White women were more likely to have elevated CA 125 than were nonwhites, but this difference was not statistically significant. Nor were any significant differences observed in comparisons by performance status grade (0 vs. 1 or 2), tumor stage (I vs. II), cell type, cytology, rupture, or patient age.
Ascites was associated with a trend toward elevated CA 125 after surgery; it was present in 76% of women with elevated levels vs. 24% with normal levels.
The investigators observed that about three-fourths of patients had normal CA 125 levels after the first cycle of chemotherapy. This led to a stratification of the population into the following three groups based on CA 125 levels:
▸ Normal before and after chemotherapy. The best outcomes were seen in women who had normal levels before and after one cycle of chemotherapy; in all, 87% were recurrence free, and 92% were alive 5 years later.
▸ Elevated before and normal after chemotherapy. In comparison, the women who had elevated levels and fell into the normal range after one cycle fared not quite as well, with 5-year recurrence and overall survival rates of 80% and 88%, respectively.
▸ Elevated before and after chemotherapy. When high CA 125 levels remained elevated after the start of chemotherapy, only 68% of women stayed recurrence free, and just 77% were alive 5 years later. These differences were statistically significant.
Dr. Kesterson said the study's limitations included a lack of information on how recurrences were treated and possible selection bias in that all cases were high risk. Among its strengths was that all patients were treated by gynecologic oncologists with comprehensive staging, central pathology review, standardized adjuvant treatment, and extended follow-up of a large number of patients.
In response to questions, he said the researchers found that whether patients received three or six cycles of chemotherapy did not affect the conclusion that an elevated CA 125 level after surgery is a significant prognostic factor for recurrence and for survival. Still to be examined, he said, is whether the interval between surgery and the start of chemotherapy could have influenced the findings.
The study was funded by the Society of Gynecologic Oncologists and the Ovarian Cancer Research Foundation.
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