CA125 Kinetics: Prognostic Value for Patients with Advanced Ovarian Cancer

Abstract & Commentary

By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.

Synopsis: A multicenter study of serial CA125 levels during chemotherapy for advanced ovarian cancer demonstrates that half-life and nadir concentration are strong and independent predictors of disease-free and overall survival.

Source: Riedinger JM, et al. CA 125 half-life and CA 125 nadir during induction chemotherapy are independent predictors of epithelial ovarian cancer outcome: results of a French multicentric study. Ann Oncol. 2006;17:1234-1238.

The tumor marker CA125 is elevated in approximately 90% of patients with epithelial ovarian cancer. The level of CA125 prior to initiation of chemotherapy for women with advanced disease has been shown to have prognostic value.1,2 In a French multicenter study investigators examined the changes in CA125 level after chemotherapy to determine if additional prognostic information could be gained. The CA125 half-life (calculated by mono-compartmental logarithmic expression), nadir CA125 concentration, and time to nadir were determined. Of the 553 patients with stage IIC to IV ovarian cancer, 459 (83%) relapsed and 444 (80.3%) died from their malignancy. The median follow-up time was 32 months (2-214 months). Prior to the first course of chemotherapy, the median CA125 level was 253 kU/L (5-52,000 kU/L) and the half-life for CA125 for this entire population was determined to be 15.8 days (4.5-417.9 days). The nadir level of CA125 was 16 (3-2610 kU/L) and the length of time to reach the nadir was 85 days (0-361 days). In univariate analysis, the pre-chemotherapy CA125 level, its half-life, the nadir concentration, and the time to nadir all had prognostic value for disease-free survival and overall survival (P < 0.0001). In Cox models, CA125 half-life, residual tumor, nadir concentration, and stage were the most powerful prognostic factors for disease-free survival. For overall survival, the significant variables were similar, but also included patient age. Thus, among the well-established prognostic factors for ovarian cancer, CA125 responses as measured by half-life and nadir concentration were shown to be of independent prognostic value.

Commentary

Assessing chemotherapy response in patients with ovarian cancer is sometimes challenging for oncologists for lack of measurable disease. However, for most patients serum level of CA125 has proven a reliable indicator of disease presence and activity.1,2 In fact, several investigators have shown that pre-treatment CA125 levels correlate with treatment response and earlier studies had suggested that serum half-life of CA1253-5 and nadir level6 were of prognostic value. Furthermore, a recent report7 demonstrated the nadir level during initial chemotherapy had predictive value with regard to the success of maintenance chemotherapy for those who were in remission.

The current French center study, by virtue of its multi-center design and number of patients, adds more. The rate of fall (half-life) and the absolute nadir of serum CA125 reached during induction chemotherapy were clearly shown to have strong and independent predictive value with regard to disease-free and overall survival. For clinical investigators, this information might prove useful in designing trials for remission maintenance upon completion of the initial course of chemotherapy. For example, one could imagine in future trials of maintenance therapy, stratifying enrolled patients on the basis of their CA 125 kinetic pattern or nadir during induction chemotherapy. Indeed, a recent report7 demonstrated the nadir level during initial chemotherapy had predictive value with regard to the success of maintenance chemotherapy for those who were in remission.

The data presented may also be useful for physicians in the community who oftentimes are faced with off-trial decisions. Patients with a sluggish CA125 response during initial therapy or a disappointing nadir level might be considered at higher risk for relapse and maintenance treatments might be designed accordingly. Data derived from aforementioned trials in which such parameters are included will ultimately lend confidence to these empiric decisions, which, for the time being, are based solely on clinician judgment.

References

1. Makar AP, et al. Prognostic value of pre- and postoperative serum CA 125 levels in ovarian cancer: new aspects and multivariate analysis. Obstet Gynecol. 1992;79:1002-1010.

2. Gard GP, Houghton CR. An assessment of the value of serum CA 125 measurements in the management of epithelial ovarian carcinoma. Gynecol Oncol. 1994;53:283-289.

3. Hawkins RE, et al. The prognostic significance of the half-life of serum CA 125 in patients responding to chemotherapy for epithelial ovarian carcinoma. Br J Obstet Gynaecol. 1989;96:1395-1399.

4. Buller RE, et al. CA 125 kinetics: a cost-effective clinical tool to evaluate clinical trial outcomes in the 1990s. Am J Obstet Gynecol. 1996;174:1241-1245.

5. Gadducci A, et al. The predictive and prognostic value of serum CA 125 half-life during paclitaxel/platinum-based chemotherapy in patients with advanced ovarian carcinoma. Gynecol Oncol. 2004;93:131-136.

6. Frasci G, et al. A risk model for ovarian carcinoma patients using CA 125: time to normalization renders second-look laparotomy redundant. Cancer. 1996;77:1122-1130.

7. Markman M, et al. Pretreatment CA-125 and risk of relapse in advanced ovarian cancer. J Clin Oncol. 2006;24:1454-1458.