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CA125 as a Marker for Ovarian Cancer Progression During Maintenance Treatment

A cutoff value of 20 U/mL for CA125 reliably predicted which women with ovarian cancer in remission would develop progressive disease.

The Gynecologic Cancer Intergroup (GCIG) has established criteria to measure disease progression in ovarian cancer patients who are undergoing treatment. The cancer antigen (CA)125 criterion defines progression as a CA125 level >2x the upper limit of normal (ULN is 35 U/mL) for patients with normal baseline CA125 levels or for those whose CA125 levels have normalized during treatment; disease progression is defined as CA125 level >2x nadir value (on 2 successive occasions) for patients whose CA125 levels have not normalized. Several investigators have reported that patients whose CA125 nadir levels are in the single digits have longer progression-free and overall survival than do patients whose nadir levels are >10 U/mL (J Clin Oncol 2006; 24:1454; J Clin Oncol 2006; 24:suppl:5059; and J Clin Oncol 2006; 24:suppl:5060). Because different "normal" CA125 nadir levels might engender different prognoses, investigators examined whether early indications of disease activity, based on nadir CA125 levels, would predict actual progression.

Researchers retrospectively evaluated data from a trial of maintenance therapy with paclitaxel in 288 patients who had achieved complete clinical response to induction therapy (J Clin Oncol 2003; 21:2460). For the retrospective analysis, they defined early progressive disease (EPD) criterion as:

• A confirmed value of >20 U/mL, if CA125 nadir <10 U/mL
  
• A confirmed value of >2x the nadir value, if CA125 nadir was >10 U/mL
  

When the EPD criterion was compared with actual progression (defined by GCIG and other criteria), the EPD predicted recurrence (median difference, 56 days before the GCIG recurrence criterion was met). Among 204 patients who developed progressive disease, 31% of patients reached the EPD criterion by <60 days before the date of progression, 15% reached it by 61 to 180 days before progression, and 10% of the patients reached it by >180 days before progression. Among 84 patients who did not develop progression, 9 reached the EPD criterion. The EPD criterion’s positive predictive value was 93% (95% confidence interval, 88%–97%). The authors concluded that the EPD criterion reflects the onset of disease progression before the GCIG criterion is met and that its use might improve early detection of progressive disease.

Comment: The authors of this study propose a criterion that could identify disease progression earlier than the currently employed criteria for progressive disease. Before validation of the EPD criterion is attempted, we must consider its clinical relevance. Currently, considerable debate continues about whether defining progression early, in the absence of symptoms or radiographic findings, is meaningful. To date, no studies have shown that early identification of disease progression and subsequent treatment lengthens survival or improves quality of life. Two ongoing clinical trials are being conducted to explore whether therapy at the time of biochemical progression improves outcomes: a Medical Research Council/European Organisation for Research and Treatment of Cancer study and a Gynecologic Oncology Group trial. In the absence of data showing that early treatment is useful and because most experts believe that recurrent ovarian cancer is incurable, immediate incorporation of the EPD criterion into clinical practice is premature. However, it could be beneficial for defining progression in clinical trial settings (e.g., comparison of different induction therapies).

— Susana M. Campos, MD, MPH

Dr. Campos is an Instructor in the Department of Medicine at Harvard Medical School and the Dana-Farber Cancer Institute in Boston, MA.

Published in Journal Watch Oncology and Hematology September 25, 2007

Citation(s):

Liu P-Y et al. An early signal of CA-125 progression for ovarian cancer in patients receiving maintenance treatment after complete clinical response to primary therapy. J Clin Oncol 2007 Aug 20; 25:3615.

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