Defining progression of ovarian carcinoma during follow-up according to CA 125: A North Thames Ovary Group study

Summary Background: Many studies have shown that CA 125 levels frequently rise prior to clinical evidence of progression of ovarian cancer. For clinical trials an accepted definition of progression according to CA 125 is required. We therefore determined what change in CA 125 level was the most accurate predictor of relapse in patients on follow up after therapy for ovarian cancer. Patients and methods: Serial CA 125 levels were studied from 255 patients entering the North Thames Ovary Trial of 5 versus 8 courses of chemotherapy. An initial analysis was made 2 months after closure of the trial, a more detailed analysis was made after 81 confirmed relapses among evaluable patients and a final analysis was made one year later with longer follow-up. Results: On the basis of the results from the interim analyses and the cut-off level of 22-35 U/ml used by different laboratories, 30 U/ml was chosen as the upper limit of normal. In the final analysis a doubling of CA 125 from the upper limit of normal was defined as progression. Using this method sensitivity was 85.9%, specificity 91.3%, positive predictive value 94.8%, and negative predictive value was 77.8%. Insisting on a confirmatory elevated CA 125 level reduced the false positive rate to <2% with a sensitivity of 83.9%. The median lead-time prior to clinical progression was 63 days. Conclusion: A confirmed rise of serum CA 125 level to more than twice the upper limit of normal during follow up after first line chemotherapy accurately predicts tumour relapse.