Monday, May 24, 2021

Ovarian cancer screening (still) doesn't save lives

 - Jennifer Middleton, MD, MPH

Five years ago, I wrote about the pitfalls of advertising ovarian cancer screening (specifically, the ROCA test) to post-menopausal persons given the dearth of evidence supporting a mortality or morbidity benefit. The primary study that I cited, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), released preliminary data in 2016. While they offered the tantalizing suggestion that ovarian and tubal cancer screening may offer a small benefit, they also acknowledged that the mortality of its participant groups did not appear markedly different. Now, after following these 200,000+ participants for a median of 16.3 years, the UKCTOCS researchers are definitively reporting no difference in mortality rates among those who were screened for ovarian and tubal cancer compared to those who were not. 

The UKCTOCS enrolled participants who were post-menopausal from across the United Kingdom and randomized them into three groups: annual multimodal screening (MMS) using ROCA, annual transvaginal ultrasound screening (USS), or no screening. The completed study, published earlier this month, found that:

Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (−41·8 to –2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (−21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group.

Although the MMS identified more cancers at an earlier stage, this early identification did not translate into a mortality benefit. In 2016, the UKCTOCS researchers responsibly advised caution regarding the risk of lead time bias in judging MMS' early detection ability; their assertion then that "follow-up is needed to assess the extent of the mortality reduction before firm conclusions can be reached on the long-term efficacy...of ovarian cancer screening" presciently predicted their final findings.

The United States Preventive Services Task Force (USPSTF) continues to recommend against ovarian cancer screening, and their rationale includes the important caveat that "screening for ovarian cancer can result in...many false-positive results, which can lead to unnecessary surgical interventions in women who do not have cancer." The Choosing Wisely campaign similarly advises against ovarian cancer screening in average risk, asymptomatic persons. As I wrote in 2016we should continue to focus our preventive care on interventions that are proven to decrease mortalityThis AFP article on "Diagnosis and Management of Ovarian Cancer" includes links to editorials that provide additional context regarding screening if you'd like to read more.