Recurrent Ovarian Cancer: 'Normal' CA-125 Status May Give False Reassurance
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Recurrent epithelial ovarian carcinoma is considered an incurable disease, and second-line chemotherapy is mainly considered for palliation of symptoms and extension of survival. There are a growing number of treatment options, and women are therefore living longer, despite having recurrent disease.
Standard of care for platinum-sensitive recurrent ovarian cancer now includes maintenance therapy with antiangiogenic agents and poly (ADP- ribose) polymerase ( PARP) inhibitors. Surveillance and accurate recognition of cancer recurrence is therefore important to guide timely subsequent treatment.
The cancer antigen (CA)-125 tumor marker is a glycoprotein expressed on the cell surface of epithelial ovarian cancer cells; levels are elevated in >80% of newly diagnosed ovarian carcinoma patients. In first-line treatment, changes in CA-125 levels are well correlated with response and survival.
In contrast, monitoring of CA-125 in second-line treatment is controversial. Many studies have concluded that there is a discordance between CA-125 with radiologic evaluation while on second-line chemotherapy.
A recent study in the is another analysis of three studies looking at concordance between CA-125 and RECIST assessment while on PARP inhibitor maintenance. The researchers combine four studies of relapsed platinum-sensitive ovarian cancer -- NOVA, ARIEL3, SOLO2, and Study 19. A total of 1,262 participants were eligible for the final analysis.
The results showed, as in many other studies, a concordance between CA-125 disease progression (PD) and RECIST PD while on platinum-based chemotherapy, particularly in the investigator-assessed population. Use of CA-125 for surveillance, however, showed it was not a good tool for detecting RECIST PD.
The authors did extensive and in-depth analysis. The conclusion of poor concordance between CA-125 and RECIST assessment while on maintenance treatment in the relapsed setting makes a strong case for periodic imaging to monitor the patient's disease status while on maintenance therapy. These findings are regardless of the type of PARP inhibitor or homologous recombination deficiency status.
The findings have significant clinical implications for future clinical trial designs. It's important to be aware that normal CA-125 may be a false reassurance to both the patient and the clinician. Periodic imaging may lead to discontinuation of potentially futile lengthy treatments, side effects, and needless costs associated with these treatments.
The limitation of the analysis is that it uses pooled retrospective data rather than prospective data. Hopefully, future clinical trials will look at this prospectively.
The finding also challenges the current NCCN guidelines recommending CA-125 monitoring if initially elevated and imaging if clinically indicated.
These results add to the growing evidence and emphasize the importance of surveillance imaging in addition to serum measurement of CA-125 in routine practice.
One of the unanswered questions is how long to continue surveillance imaging, especially in the few patients whose second remission is longer than the first. Further research is also necessary to determine if early intervention offered to women with early asymptomatic radiological detected PD will prolong overall survival.
Veena John, MD, is system head in Gynecologic Medical Oncology at Northwell Cancer Institute and associate professor at Zucker School of Medicine at Hofstra/Northwell Zuckerberg Cancer Center in Lake Success, New York.
Read the study here and an interview about it here.
Primary Source
Journal of Clinical Oncology
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