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First Cycle CA-125 Response Predicts Favorable Outcome for Ovarian Cancer Patients
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: In a large series of ovarian cancer patients treated with chemotherapy after primary laparotomy, the fall in CA-125 during the first and second cycles was shown to provide significant prognostic value. This simple determination may prove useful in selecting patients to receive more intensive or prolonged maintenance chemotherapy after the initial induction courses are completed.
Source: Riedinger JM, et al. Change in CA 125 levels after the first cycle of induction chemotherapy is an independent predictor of epithelial ovarian tumor outcome. Ann Oncol. 2007;18:881-885.
Measurement of serum CA-125 has proven to be a useful indicator of prognosis for patients with ovarian cancer. Riedinger and colleagues in France conducted a mulitcenter retrospective analysis to assess the prognostic value of the CA-125 change after the first and second courses of induction chemotherapy. At the participating eight cancer centers there were 494 eligible stage (International Federation of Gynecology and Obstetrics [FIGO]) IIc-IV epithelial ovarian cancers treated between 1988 to 1996, and their clinical course was followed to the study end in May, 2005. All patients had a primary laparotomy followed by a minimum of six cycles of chemotherapy (cyclophosphamide and platinum; no patients in this series received taxane). CA -125 was measured before the first cycle of chemotherapy (baseline) and prior to each subsequent cycle.
At the time of primary laparotomy, 142 patients (28.7%) had no apparent residual disease, 123 (24.9%) had a residual disease of ≤ 1 cm in the largest diameter, and 229 (46.4%) had a residual disease >1cm. After six cycles of chemotherapy, a second look laparotomy was carried out in 194 stage III patients who were considered to be in clinical complete remission (cCR). Of these, 111 (57.2%) showed a pathological CR (pCR) while 83 (42.8%) showed incomplete response.
During the first cycle of chemotherapy the median change in CA-125 was a 65% decrease, but with a wide range (82% increase to 99% decrease). Similarly in the second cycle the median was a 61% decrease in CA-125 (133% increase to 98% decrease). The total change from baseline through the first two cycles was an 86% decrease (115% increase to 100% decrease).
The CA-125 level before the 3rd cycle of chemotherapy was found to bear a prognostic value for overall survival (OS): median OS was 1.9 years (1.6-2.1 years) for patients with a CA-125 > 35kU/L and 4.9 years (4.0-5.4 years) for patients with a CA-125 ≤ 35kU/L (hazard ratio [HR] = 2.7 (2.2-33.3; P < 0.0001). By univariate analysis, the changes in CA-125 during the first, second, and the sum of first and second cycles, and the absolute CA-125 level before the third cycle each had strong prognostic value for OS (all with P < 0.0001). In multivariate analysis, the change in CA-125 level during the first chemotherapy course (P < 0.0001), the absence of residual tumor mass (P < 0.003), and the CA-125 level before the second course (P = 0.037) were found to be independent prognostic variables. Furthermore, among the 194 stage III patients who underwent second look laparotomy, the frequency of pCR was 77.2% (61 of 79) in the subgroup defined by those who had a >50% reduction in CA-125 during the first cycle and a return to the normal range during the second cycle of chemotherapy. Thus, the initial change in CA-125 level after the first and second cycles of chemotherapy define a subgroup of patients with more favorable prognosis.
Serum CA-125 level has become a very useful clinical tool for those treating ovarian cancer.1,2 Just a few months ago in these pages we reviewed a retrospective analysis of maintenance chemotherapy conducted by the Southwest Oncology Group (SWOG) and the Gynecologic Oncology Group (GOG), in which the baseline CA-125 level just prior to the initiation of maintenance chemotherapy was found to strongly predict the risk of recurrence. Those with CA-125 levels ≤ 10u/mL were found to have a superior progression free survival (PFS) compared with higher CA-125 levels within the normal range.3 The current report adds yet another twist. The rapidity and magnitude of the CA-125 response to the first and second cycles of chemotherapy can be used to define subgroups with varying chances of achieving pCR and prolonged overall survival. This may prove particularly useful as cooperative groups are now exploring prolonged maintenance therapy for some patients considered at higher risk for recurrence. Factors such as the rate of decline in CA -125 during the first two cycles of initial chemotherapy and the absolute level just prior to the initiation of maintenance therapy may be useful in distinguishing those who should receive more intensive and prolonged maintenance treatment and those who might do well with lesser treatment.
One small caveat with regard to the current report is worth mentioning. Taxanes were not part of the treatment regimen at the time the data was recorded and it is possible that this active drug, now used in front line treatment for ovarian cancer, could have a different effect on CA-125 kinetics. This bears attention, and hopefully this French group, or other experts in CA-125 kinetics, will provide similar data using the more current chemotherapy combinations.
1. Gard GB, 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.
2. 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.
3. Markman M, et al. Pretreatment CA-125 and risk of relapse in advanced ovarian cancer. J Clin Oncol. 2006;24:1454-1458.