Contrary to popular belief, starting chemotherapy early does not improve survival or quality of life compared with postponing treatment until clinical symptoms of relapse are evident in women with ovarian cancer. These are the findings of the first randomised trial to investigate timing of treatment for relapsed ovarian cancer published in an Article in this week's Cancer Special Issue of The Lancet.
The level of the CA125 protein produced by ovarian cancer cells in the blood often increases several months before signs or symptoms of relapse appear in women with ovarian cancer. Current practices concerning whether or not regular CA125 tests are done and when to start second-line chemotherapy vary widely. Additionally, concerns about CA125 testing and the implications of positive results can cause patients considerable anxiety.
The Medical Research Council (MRC) OV05 and European Organisation for Research and Treatment of Cancer (EORTC) 55955 trials were established to compare the benefits of early treatment on the basis of rising CA125 levels versus delaying treatment until clinical or symptomatic relapse.
1442 women in complete remission with ovarian cancer were enrolled in the trial. Clinical examinations and a CA125 blood test were done every 3 months. If CA125 level increased to twice the upper limit of normal, patients were randomly assigned to early (treatment starting as soon as possible) or delayed (treatment starting when signs or symptoms of relapse were detected) chemotherapy. A total of 529 women were randomly assigned to treatment—265 to early and 264 to delayed.
After a median follow-up of 56•9 months, no difference in overall survival was shown between early and delayed treatment—370 women died, 186 in the early treatment group and 184 in the delayed group.
Median survival after randomisation was 25•7 months for patients having early treatment and 27•1 months for those having delayed treatment.
Additionally, quality of life deteriorated sooner in patients being treated earlier, with significant disadvantages for role, emotional, social, and fatigue associated with early treatment.
The authors say: "Women should be informed that there is no evidence of a benefit from early treatment on the basis of rising CA125 concentration, and no deterioration in quality of life by delaying chemotherapy. If CA125 concentration rises during follow-up, chemotherapy can be safely delayed until symptoms or signs of tumour recurrence develop."
They conclude: "For the first time women can be given evidence-based advice and can make informed choices about follow-up…The results of this trial suggest that they can opt to forgo routine CA125 monitoring if their disease is in complete remission after first-line treatment."
In a Comment, Robert Morris from Wayne State University in Detroit and Bradley Monk from Creighton University School of Medicine in Arizona, USA, say: "This clinical trial should be appreciated for its bold challenge to the assumption that early treatment of relapsed disease must be better than delayed treatment. Indeed, the article provides some evidence that early retreatment might be detrimental. Rustin and colleagues should be commended on this endeavour, which, like other provocative studies, begs more questions than it answers. From their study, principles that we have considered fundamental are deservedly brought into question."
Cathy Beveridge, Medical Research Council Senior Press Officer, London, UK. T) +44 (0)20 7670 5138 E) catherine.beveridge@headoffice.mrc.ac.uk
Dr Robert Morris, Wayne State University, Detroit, USA. T) +1 313 576 9435 E) rmorris@med.wayne.edu
For full Article and Comment see: http://press.thelancet.com/ovar.pdf
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Journal
The Lancet