A hope that Ovarian Cancer screening may save lives!

A hope that Ovarian Cancer screening may save lives!

Each year, about 20,000 women in the United States get ovarian cancer.

Ovarian cancer accounts for approximately three percent of cancers in women. Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system.

A woman’s lifetime risk of developing invasive ovarian cancer is 1 in 75. A woman’s lifetime risk of dying from invasive ovarian cancer is 1 in 100.

Ovarian cancer rates are highest in women aged 55-64 years. The median age at which women are diagnosed is 63, meaning that half of women are younger than 63 when diagnosed with ovarian cancer and half are older.

Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years.

image courtesy: seers data

The American Cancer Society estimates for ovarian cancer in the United States for 2015 are:

•     About 21,290 women will receive a new diagnosis of ovarian cancer. 
•   About 14,180 women will die from ovarian cancer.

 A paper published on-line in Lancet on December 17, 2015, gives us the first evidence that screening can save lives from ovarian cancer as a paradigm shift in our approach to the disease.

UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is a Randomized control trial which recruited more than  200,000  postmenopausal women aged 50–74  from June 2001 to October 2005

The women were assigned to one of the following three groups in the ratio of 1:1:2

• 50,624 underwent annual multimodality screening, which consisted of a serum cancer antigen 125 (CA125) test interpreted with the risk of ovarian cancer algorithm (ROCA) plus ultrasound;
• 50,623 underwent annual transvaginal ultrasound screening alone;
• 101,299 underwent no screening.

The women in 13 centers in UK followed for nearly 14 years with a median of 11.1 year.  

Annual screening in the MMS group used serum CA125 concentration testing, with the pattern over time interpreted with use of the risk of ovarian cancer calculation ( ROCA), which identifies significant rises in CA125 concentration above baseline.

Next, ROCA triaged women to normal (annual screening), intermediate (repeat CA125 concentration testing in 3 months), and elevated (repeat CA125 concentration testing and

transvaginal USS as a second-line test in 6 weeks) risk

Annual screening in the USS group used transvaginal USS as the primary test, which was classified as normal (annual screening), unsatisfactory (repeat in 3 months), or abnormal (scan with a senior ultrasonographer within 6 weeks).

In both groups, women with persistent abnormalities had clinical assessment and additional

investigations within the NHS by a trial clinician.

The primary outcome was ovarian cancer death by Dec 31, 2014, secondary outcome was death due to ovarian and primary peritoneal cancer. 

At a median follow-up of 11.1 years (interquartile range, 10.0 - 12.0), ovarian cancer had been diagnosed in 1282 (0.6%) women — 338 (0.7%) in the multimodality group, 314 (0.6%) in the ultrasound group, and 630 (0.6%) in the no-screening group.

When the researchers analyzed the 14-year data, they found a reduction in the rate of death from ovarian cancer of 15% (95% confidence interval [CI], –3 to 30; P = .10) in the multimodality group and of 11% (95% CI, –7 to 27; P = .21) in the ultrasound group.

The screening test involves a simple blood test, which can be done anywhere and sent to a lab," he said. This could have an effect on the more than 100,000 deaths from ovarian cancer each year around the world.
Overall, there was an average reduction in mortality of 20% in favor of multimodality screening. The reduction in mortality was 8% in the first 7 years and 28% in the subsequent 7 years.

Cancer was detected at an early stage in more patients in the multimodality group than in the no-screening group (39% vs 26%; P < .0001).

Experts opinions on the trial 

This is the first-ever evidence to suggest that screening for early detection of ovarian cancer may save lives," said Ian Jacobs, MD, president and vice-chancellor of the University of New South Wales in Sydney, Australia , in a news bulletin.

"More follow-up is needed, but the results are encouraging and exciting and open up the possibility that many lives could be saved," said Dr Jacobs, who led the trial with Usha Menon, MD, from the Institute for Women's Health, University College London, United Kingdom.

"Research now needs to accelerate to refine screening and confirm the benefit, so that, in due course, widespread national screening programs can be put in place," Dr Jacobs said.

"We have the first evidence that ovarian cancer screening can save lives, but we need further follow-up to confirm the findings," added Dr Menon.

"However, screening is not without harms, which include some women undergoing surgery to find they only have benign ovarian lesions or normal ovaries," she told Medscape Medical News.

Experts agree that longer follow-up is needed to determine how effective annual screening will turn out to be.
"Although still at an early stage, the initial results from the UKCTOCS trial into screening for ovarian cancer are promising," Clare Mckenzie, MD, consultant gynecological oncologist and vice president of the Royal College of Obstetricians and Gynaecologists, said in a statement.

Gary S. Leiserowitz, MD, professor and chair of the Department of Obstetrics and Gynecology, and chief of the division of gynecologic oncology at the University of California Davis Health System in Irvine commented that  "Two other studies — one from Japan and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial from the United States — were smaller, and neither showed statistically significant benefits to large-scale ovarian cancer screening. The UK trial showed some evidence of early detection with both multimodality and ultrasound, plus moderate reduction of mortality using post hoc statistical analyses. The effects were greater with longer follow-up."

So far, results suggest that approximately 15 deaths could be prevented with CA125 screening for every 10,000 women screened, Dr Mckenzie noted. "However, for every woman with a positive screen who underwent surgery and was found to have ovarian cancer, two did not," she added.

Karen H. Lu, MD, chair of gynecologic oncology and reproductive medicine at the University of Texas M.D. Anderson Cancer Center in Houston said that “I believe that while the results from UKCTOCS are not practice-changing right now, they have a very real potential of being practice-changing in the near future."

Conclusion.

Key strengths of this trial include scale, with more than 202000 participants, more than 670000 annual screening episodes, and more than 2·19 million women-years of  follow-up; the multicentre setting within the UK NHS.

The main limitation of this trial was failure to anticipate the late eff ct of screening in the statistical design.

Implications of all the available evidence --Our findings suggest that a multimodal approach to screening might detect ovarian cancer sufficiently early to reduce mortality. To establish the magnitude of this reduction in deaths, a longer duration of follow-up is needed. Meanwhile, efforts to refine ovarian cancer screening strategies should continue.

References:
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2901224-6/abstract
http://www.cdc.gov/cancer/ovarian/statistics/
http://www.ovariancancer.org/about/statistics/
http://www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-key-statistics
http://www.medscape.com/viewarticle/856099#vp_1