The trial by Rustin et al in women with ovarian cancer in complete clinical remission following primary treatment, found no evidence that early initiation of chemotherapy for recurrence based on rising CA125 concentrations improves survival or quality of life, compared with delaying chemotherapy until clinical or symptomatic recurrence is evident (median follow-up of 57 months from randomisation).22
In this multicentre study of over 1,400 women recruited from the UK, Europe and South Africa between 1995–2005, clinical examination and CA125 measurement was undertaken every three months. The strength of this study was that it was a prospective randomised trial, however some limitations of the study have been noted.23-25 Patients and clinicians were blinded to CA125 results which were monitored by coordinating centres. Once CA125 levels were elevated beyond twice the upper limit of normal, 529 patients were randomised to either early treatment (n=265) or treatment delayed until clinical or symptomatic recurrence was evident (n=264).
Fifty three percent and 79% of women were recruited within 12 and 24 months of completion of first line chemotherapy respectively. Nineteen percent of the study population had originally been diagnosed with early stage disease (FIGO I or II). Data on optimal debulking rates from primary surgery were not provided. Subgroup analysis adjusted for stratification and prognostic factors showed no difference in treatment effect by treatment group. However the study was not sufficiently powered to analyse the effect of time from first-line treatment to randomisation, or timing to second-line treatment.
In assessing quality of life, the study by Rustin et al22 found that women in the delayed treatment arm reported good global health scores for longer than those in the early treatment arm (for 9.2 months compared to 7.2 months). Subgroup analyses using components of the EORTC QLQ-C30 subscales showed deterioration in scores for almost all subscales occurred sooner for women in the early treatment arm compared to the delayed group. There was evidence of significant disadvantage for role, emotional, social and fatigue measures for women in the early treatment arm compared to women in the delayed treatment arm.22
The routine measurement of CA125 during follow-up for all women treated for ovarian cancer has pros and cons. Rustin’s study22 questions the routine use of CA125 in surveillance, and challenges the widespread belief that early treatment of recurrent disease must be better. For women who encounter early relapse of their cancer, routine CA125 measurement is not beneficial. There are however concerns that it is premature to conclude that surveillance of all women using CA125 should be abandoned.25 It is suggested that some women with ovarian cancer may benefit from the detection of subclinical recurrence, particularly those who are eligible for secondary cytoreductive surgery.
The key findings of the Rustin study include:
- There is no evidence of survival benefit for women who commenced early chemotherapy for first relapse based on raised CA125 levels alone
- Less deterioration in quality of life was reported among women who delayed chemotherapy until clinical or symptomatic recurrence was evident
Complete cytoreduction at the time of surgery for recurrence is strongly linked to improved survival.26,27 The Desktop II study prospectively validated a scoring system predicting complete secondary cytoreduction in women with recurrent ovarian cancer. Predictive factors included women with platinum sensitive recurrent disease, without ascites, in whom complete resection of disease was obtained at first line surgery and who have a good performance status.28 The AGO-OVAR Desktop III randomised trial aims to evaluate the role of secondary cytoreductive surgery for recurrent ovarian cancer.
The key findings of the Desktop II study support that:
- Some women may benefit from routine measurement of CA125, including those who are eligible for secondary cytoreductive surgery,
Defining women who are likely to benefit from measurement of CA125 is challenging and in the absence of data it is suggested women who are eligible for secondary cytoreductive surgery at relapse, should continue to be offered CA125 follow-up. Other women who may benefit from routine CA125 measurement are those taking part in clinical trials and those for whom intensive clinical follow-up is not practical.25
A qualitative study of 20 Australian women with advanced ovarian cancer found that women apply different meanings to CA125 surveillance results, including as an indicator of cancer recurrence; as an indicator of the effectiveness of treatment and/or self-care; and as an indicator of wellness. These meanings may support or challenge the woman’s experience of her symptoms, and may complicate communication and decision-making about resuming treatment.3
Jordens et al noted the psychological burden of awareness of subclinical recurrent disease. Delaying subsequent chemotherapy until clinical or symptomatic recurrence is evident enables the woman to extend her experience of remission and delay her experience of recurrence.3
- The decision to initiate re-treatment requires careful consideration based on the individual woman’s situation, and factors including the nature of the recurrence and the wishes of the woman.
- Women should be fully informed of the pros and cons of routine measurement of CA125 during follow-up and supported to make an informed decision, considering the findings of the randomised controlled trial on follow-up after ovarian cancer.