Pretreatment CA125 and Risk of Relapse in Advance Ovarian Cancer

Abstract & Commentary

By Robert L. Coleman, MD, Associate Professor, University of Texas; M.D. Anderson Cancer Center, Houston, is Associate Editor for OB/GYN Clinical Alert.

Dr. Coleman is on the speaker’s bureau for GlaxoSmithKline, Bristol-Myers Squibb, and Ortho Biotech.

Synopsis: The baseline CA125 level before initiation of maintenance chemotherapy strongly predicts the risk of subsequent relapse.

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

It has been recently identified that NADIR values in serial CA125 values during adjuvant primary post-operative chemotherapy are prognostic even within the normal range (less than 35). Markman and colleagues set out to determine if a similar finding might be observed in evaluating the outcomes of patients entered into clinical trials evaluating the efficacy of maintenance therapy. Two trials were included in the current report: GOG-178/SWOG-9701, a phase III randomized study which evaluated paclitaxel (3 vs 12 cycles) and SWOG-9386, a single-arm open-label phase II trial that evaluated altretamine in patients with complete clinical response.

Consistent with the adjuvant study, the authors of the current study defined 3 categories of CA125 (≤ 10 u/mL, 11-20 u/mL and 21 to 35 u/mL). In addition to CA125, residual disease and age were considered in the final analysis. Similar to the previous report, patients with pre-registration CA125 values of 10 or less were associated with the best survival. This was observed in each of the 3 cohorts and in both studies. Overall, median PFS was 24 months, 17 months, and 7 months in the three CA125 groups. Of interest, in the randomized trial (GOG-178/SWOG-9701), the effect amounted to an improvement (12 cycles vs 3 cycles) of 9 months, 4 months, and 0 months in the 3 CA125 groups. The authors concluded that pre-treatment CA125 strongly predicts relapse in patients with complete clinical response following primary adjuvant chemotherapy.

Commentary

Most patients and clinicians are acutely aware of the prognostic significance a normal CA125 implies following therapy. It has also been recognized that patients will typically manifest a nadir value from which serial determinations are compared in estimating recurrence. Sequentially doubling of these values even within the normal range (35 u/mL or lower) has been used as a surrogate of disease recurrence even in the absence of measurable disease. In addition, a provocative recent finding is that the value of this nadir is prognostic of recurrence.

The current trial expands this line of investigation by documenting a similar prognostic effect in pre-treatment CA125 values for patients with a clinical complete response undergoing maintenance chemotherapy. No difference in effect was observed between agents or among the treatment arms. The magnitude of the observed differences by CA125 category was impressive and amounted to nearly a year and a half. Perhaps even more provocative, in the randomized trial, the observations in PFS demonstrated that no difference was observed between the 12-month and 3-month arms for patients with CA125 values of 21-35 u/mL.

While the data are retrospective and not properly powered to determine the effect, they provides some insight into a potentially important factor by which patients may be identified who could benefit most from the maintenance strategy. Prospective trials with defined CA125 stratification will help to shed light on this important prognostic variable. Since maintenance therapy is not without complication, improving the precision of therapy will be a welcomed clinical finding.