BACKGROUND AND PURPOSE:

• Among a general population, Menon et al. (The Lancet, 2021) compared 2 ovarian cancer screening approaches (multimodal and ultrasound only)

METHODS:

• Randomized controlled trial
  • UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)
  • Recruited between April 2001 and September 2005
• Participants
  • Postmenopausal
  • 50 to 74 years
  • Excluded: Bilateral oophorectomy | Previous ovarian or active non-ovarian malignancy | Increased familial ovarian cancer risk
• Interventions
  • Annual multimodal screening (MMS): Serum CA125 measurements using the ‘risk of ovarian cancer’ (ROCA) calculation | Triaged to normal (annual screening); intermediate (repeat CA125 ROCA test in 3 months); elevated (repeat CA125 ROCA test and transvaginal ultrasound (TVS) as a second-line test in 6 weeks)
  • Annual transvaginal ultrasound screening (USS): Primary screening done with TVS | Classified as normal (annual screening); unsatisfactory (repeat in 3 months); abnormal (scan with a senior ultrasonographer within 6 weeks)
  • No screening
• Study design
  • Participants were randomly allocated, in a 1:1:2 ratio, to an intervention group
  • Follow-up was through national UK registries
  • Analyses were by intention to screen: Comparing MMS and USS separately with no screening
  • Masking: Investigators and participants were aware of screening type but outcomes review committee were not
• Primary outcome
  • Death due to ovarian or tubal cancer (WHO 2014 criteria)

RESULTS:

• 202,562 women
  • MMS group: 25.0% | USS group: 25.0% | no screening group: 50.0%
  • Median follow-up of 16.3 (IQR 15.1 to 17.3) years
• 2055 total women were diagnosed with tubal or ovarian cancer
  • MMS: 1.0% of the group
  • USS: 1.0% of the group
  • No screening: 1.0% of the group
• Compared with no screening, the MMS group experienced
  • Increased stage I incidence: 47.2% (95% CI, 19.7 to 81.1)
  • Decreased stage IV incidence: -24.5% (95% CI, -41.8 to -2.0)
• Overall the incidence of stage I or II disease was higher in the MMS group compared to the no screening group
  • 39.2% (95% CI, 16.1 to 66.9)
• Incidence of stage III or IV disease was lower in the MMS group compared to the no screening group
  • -10.2% (95% CI, −21.3 to 2.4)
• Tubal and ovarian cancer mortalities
  • MMS: 0.6%
  • USS: 0.6%
  • No screening: 0.6%
• There was no significant reduction in ovarian and tubal cancer deaths in the MSS (P=0.58) or USS (P=0.36) group compared to no screening

CONCLUSION:

• While there was an approximately 10% reduction in incidence of stage III or IV ovarian cancers with MSS screening, there was no difference in ovarian cancer mortality with either screening type
• The authors state

General population screening for ovarian and tubal cancer with either of the screening strategies cannot be recommended based on evidence to date

The changes in stage distribution in the MMS group did not translate into mortality reduction, emphasising the importance of having disease-specific mortality as the primary outcome in ovarian cancer screening trials

Achieving a mortality reduction will require a screening strategy that can detect ovarian and tubal cancer even earlier and in a larger proportion of women than we were able to achieve

In the MMS group of UKCTOCS, it seems probable that the cancers shifted to an earlier stage had an intrinsic poor prognosis, which was not altered by earlier detection and the available treatments for early stage disease

Learn More – Primary Sources:

Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

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