CA-125 Level Predicts Outcome of Maintenance Chemotherapy for Ovarian Cancer in Remission

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: There has been a suggestion that the level of CA-125 for ovarian cancer patients who are in complete remission predicts the risk of relapse. In a retrospective analysis of maintenance chemotherapy for this disease conducted by the Southwest Oncology Group (SWOG) and the Gynecologic Oncology Group (GOG), Markman and colleagues found that the baseline CA-125 level before maintenance chemotherapy (with either three or 12 monthly cycles of paclitaxel or oral altretamine) strongly predicts the risk of recurrence. Those with CA-125 levels ≤ 10 u/mL were found to have a superior progression free survival (PFS) compared with higher CA-125 levels within the normal range. Thus the CA-125 level prior to the initiation of maintenance chemotherapy may prove a useful parameter for future clinical trials addressing a major unresolved issue in ovarian cancer: optimal treatment for maintenance of remission.

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

For patients with advanced ovarian cancer, platinum-taxane-based chemotherapy has proven successful in achieving a high level of disease remission, but, unfortunately, in the great majority, relapses occur.1 Accordingly, there has been an increased interest in developing maintenance chemotherapy strategies to enhance progression-free survival (PFS). It has been proposed that a possible predictor of successful maintenance chemotherapy is a very low level of serum CA-125 prior to the initiation of maintenance chemotherapy. Typically, one criterion for complete remission after initial chemotherapy for advanced ovarian cancer is the normalization of the CA-125 level and currently most oncologists do not choose the chemotherapy agents or duration of therapy on the basis of the CA-125 level. Thus, patients with a level of 5 u/mL will typically receive the same treatment as those with levels closer to the upper limit of normal (near 35 u/mL). In the current report, Markman and other investigators of the Southwest Oncology Group (SWOG) and the Gynecologic Oncology Group (GOG) conducted a retrospective analysis of two previously reported trials of maintenance chemotherapy (3 vs 12 monthly cycles of paclitaxel; oral altretamine). All patients were in complete remission and all had a baseline CA-125 level of less than 35 u/mL. For the purpose of analysis, patients were identified as in one of three groups based upon their pretreatment CA-125 level: A) ≤ 10 u/dL; B) 11-20 u/dL; or C) 21-35 u/dL. PFS from study entry was analyzed by the Cox regression model.

The distribution of pre-maintenance baseline CA-125 levels for 384 patients was 58% less than or equal to 10 u/mL, 34% between 11 and 20 u/mL, and 8% between 21 and 35 u/mL. The baseline CA-125 was highly significant either as a categoric variable (P < 0.001) or as a continuous variable (P < 0.0001). Median PFS was 24 months, 17 months, and 7 months for groups A, B, and C noted above respectively. Although the patients were enrolled from different trials, there was no evidence that the CA-125 level effect differed by treatment using an interaction analysis. Thus, the baseline CA-125 level before initiation of maintenance chemotherapy was found to strongly predict the risk of subsequent relapse. The patients with pre-maintenance baseline CA-125 values of ≤ 10 u/mL have a superior PFS compared with higher levels in the normal range.

Commentary

It is apparent that maintenance chemotherapy for those who achieve complete remission after primary chemotherapy for advanced ovarian cancer has a role in improving overall survival. However, it is not yet clear which drugs to use, and for how long. Furthermore, in the context of added toxicities and infringements on quality of life, it is not absolutely clear that the improvements in PFS are of sufficient magnitude to warrant uniform recommendation at this time. Thus, the availability of information relating the likelihood of relapse and expected remission duration to a pretreatment serum marker is likely to be considered valuable by both physician and patient.

The current report provides significant insight in this regard. For those who completed initial therapy and prior to maintenance were found to have a low CA-125 level (≤ 10 u/mL), the PFS was significantly longer in each of the various treatment schedules examined in this analysis. Higher pretreatment CA-125 levels were associated with shorter durations of remission. Why should this be? One likely explanation is that those with very low levels of CA-125 have a smaller tumor burden. Another is that they have more chemosensitive tumors. Of course, in a retrospective analysis such as this, it would be impossible to discern these or other explanations; perhaps this will be addressed in future investigations. Nonetheless, clinicians might find the observation of practical value while formulating post-remission plans for their patients.

Furthermore, clinical investigators attempting to define optimal maintenance chemotherapy regimens might be advised to consider and perhaps stratify on the basis of the pretreatment CA-125 level.

Reference

1. Ozols RF, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003;21:3194-3200.