UK Collaborative Trial of Ovarian Cancer Screening
Does screening for ovarian cancer help save lives by detecting the disease earlier?
What is this study about?
Ovarian and tubal cancers are the leading cause of death from gynaecological cancers in the UK. This is related to diagnosis at advanced stage. When women are diagnosed earlier, they have a much better survival – over 90% of Stage I patients are alive five years after diagnosis compared to 4% of Stage IV patients. This suggests that screening may help save lives by detecting the disease earlier.
The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) was designed to test this hypothesis. Between April 2001 and September 2005, 202,638 postmenopausal women, aged 50-74 years were recruited through 13 trial centres in England, Wales and Northern Ireland. Women were randomly allocated to one of three groups (i) no screening or control (C) - no screening (ii) multimodal screening (MMS) - annual blood test for serum CA125 measurement. The results were interpreted using the ‘Risk of Ovarian Cancer Algorithm’, with women undergoing repeat blood tests for CA125 and transvaginal ultrasound if results were not normal (iii) ultrasound screening (USS) – annual transvaginal (internal) ultrasound scan with the scan repeated if results were not normal.
Women were linked via their individual NHS numbers to national cancer and death registries in England, Wales and Northern Ireland as well as administrative databases such as Hospital Episode Statistics and National Cancer Intelligence Network. Records of women identified as having a possible ovarian cancer based on a specified list of disease codes were retrieved and reviewed by an independent outcomes committee who confirmed the final outcome.
Women in the screen arms underwent 673,765 annual screens till 31 December 2011. For every woman found to have ovarian or tubal cancer on screening, 2 additional women in the multimodal group and 10 additional women in the ultrasound group had surgery where the ovaries were only found to have benign lesions or were normal. The surgical complication rate of these additional operations was around 3.1% (multimodal) and 3.5% (ultrasound) which matches the standard complication rate for such surgery. In addition, while screening did not raise anxiety, levels of worry were higher in women who had abnormal results at the annual screen and required additional tests. Rarely women had complications related to having a blood test or an internal scan such as pain, bruising or cystitis.
On 31st Dec 2015 at a median follow-up of 11.1 years per woman, the initial mortality analysis was undertaken and the results published in The Lancet. Compared to the no screening group, there was significant increase in number of women diagnosed with stage I and II ovarian and tubal cancer in the multimodal but not in the ultrasound group. The average reduction in ovarian and tubal cancer deaths was 15% in multimodal group and 11% in ultrasound group compared to control group but this was not definitive (statistically significant). The final extent of reduction was uncertain as the ovarian cancer death rates seemed to be increasing in the no screening group and levelling off in the multimodal and ultrasound groups.
Following censorship on 30 June 2020, at a median follow-up of 16.3 years per woman, the final mortality analysis was undertaken. The final results published in The Lancet showed that compared to the no screening group, there was a 39% increase in the incidence of women diagnosed with Stage I and II ovarian and tubal cancer and a 10% decrease in incidence of those diagnosed with Stage III and IV disease in the multimodal group. There was no difference in stage in the ultrasound group compared to the no screening group. There was however no reduction in deaths due to ovarian and tubal cancer in the multimodal or the ultrasound group compared to the no screening group.
The reduction in stage III and IV incidence in the multimodal group was not sufficient to translate into lives saved. This illustrates the importance of specifying cancer deaths as the primary outcome in screening trials. Given that screening did not reduce ovarian and tubal cancer deaths, currently general population screening cannot be recommended.
Type of study
Who is funding the study?
Where is it taking place?
13 trial centres in England, Wales and Northern Ireland.
Who is included?
Postmenopausal women, aged 50-74 years.