The UKCTOCS is a collaborative research initiative, coordinated by University College London (UCL), that involved 202,638 women; hundreds of healthcare professionals; 13 centers in England, Northern Ireland and Wales; the National Health Service and four major U.K. funding agencies: Medical Research Council, Cancer Research UK, the National Institute of Health Research and The Eve Appeal.
"The evidence from UKCTOCS suggests that carefully conducted screening using a multimodal strategy detects ovarian cancer sufficiently early to alter the natural history of the disease and reduce mortality," said co-principal investigator Professor Ian Jacobs, President and Vice-Chancellor of University of New South Wales Australia and Honorary Professor at UCL, who co-invented the Risk of Ovarian Cancer algorithm (ROCA) in 1996, which was used as part of the multimodal screening arm of this study. "We are excited and encouraged by these results, demonstrating an estimated mortality reduction attributable to ovarian cancer screening of 15 to 28 percent. Further follow up in UKCTOCS will provide greater confidence about the precise reduction in mortality which is achievable."
Study participants were randomly assigned to a control group (n=101,299) who received no screening and a screening group (n=101,247). The screening group was divided into two arms: a multimodal screening (MMS) group (n=50,624) and an ultrasound screening (USS) group (n=50,623). Women in the multimodal group had a blood test to assess levels of cancer antigen 125 (CA-125), the outcome of which was evaluated by ROCA to assign a woman's level of risk for ovarian cancer. If the risk was classified as intermediate or elevated, repeat blood tests and/or a transvaginal ultrasound (TVUS) scan of the ovaries were used. Women with an intermediate classification were referred for a repeat CA-125 test in 12 weeks and administered a TVUS scan if they received three intermediate ROCA scores. Women assessed with advanced risk received a TVUS scan within six to eight weeks without receiving additional blood testing.
Ovarian cancers were diagnosed in 630 (no screening), 338 (MMS) and 314 (USS) women. A Cox statistical analysis indicated a mortality reduction over years 0-14 of 15 percent with MMS, and 11 percent with USS, which were not significant. This mortality reduction was made up of an 8 percent and 23 percent relative reduction during years 0-7 and 7-14 respectively in the MMS versus no screening analysis, the reduction in the years 7-14 being statistically significant; and of 2 percent and 21 percent respectively in the USS group. The median follow-up was 11.1 years.
An additional statistical analysis was performed after excluding women who had undiagnosed ovarian cancer when they joined the trial that demonstrated there was a significant reduction in deaths with an average mortality reduction of 20 percent overall and 28 percent in years 7-14. There was also a significant reduction in deaths in the MMS versus no screening group using a separate analysis (weighted log rank test).
"I am delighted that the UKCTOCS results suggest that early detection by screening may reduce mortality," noted Steven Skates, Ph.D., researcher at Massachusetts General Hospital and contributing study author. "We look forward to ongoing analysis of this study population in order to more fully understand how a multimodal, algorithm-dependent ovarian cancer screening program might specifically affect disease diagnosis and management."
Trial results suggested that approximately 15 ovarian cancer deaths could be prevented for every 10,000 women who attend a screening program that involves annual blood tests for between seven to 11 years.
Study findings also confirmed previous results showing that, on average, for every three women who had surgery as a result of an abnormal screen, one woman had ovarian cancer while two women did not. For those who had surgery, approximately three percent had major complications, which is consistent with the standard complication rate for this type of surgery.
"These landmark findings, suggesting that a multimodal screening approach for ovarian cancer may reduce mortality, have the potential to transform clinical practice and may enable earlier diagnosis when a therapeutic intervention is more likely to be effective," said Julie Barnes, Ph.D., CEO of Abcodia. "We congratulate the entire UKCTOCS team for their tireless dedication to the study. This represents a significant step forward for a historically difficult to diagnose disease with limited treatment options and we are excited to see additional outcomes from the ongoing follow up period."
Studies show that 92% of women diagnosed at Stage 1 survive for five or more years, compared to only 18% of women diagnosed with Stage 4 disease.[i] [ii] Because ovarian cancer frequently has either non-specific or no symptoms, women are most commonly diagnosed with advanced (Stage 3 or 4) disease.
ROCA has been evaluated in several prospective studies, the largest being UKCTOCS. Earlier results from UKCTOCS, published in Journal of Clinical Oncology in May 2015 revealed that multimodal screening using ROCA as the first line test, triggering a transvaginal ultrasound scan as required, reported a sensitivity of 85.8% and specificity of 99.8% for detection of ovarian cancer.[iii] The sensitivity of ROCA compared favorably to the use of CA-125 alone, which would have identified only 41.3% to 66.5% of ovarian cancers, (depending on the threshold value used).
Abcodia Ltd is a clinical stage company engaged in the commercial development of novel tests for the early detection of cancer. The Company's first product is the ROCA Test for the early detection of ovarian cancer, and it is expanding its pipeline of early detection technologies for lung, colorectal and pancreatic cancer. Abcodia's offerings are based on expertise in measuring and modelling dynamic changes over time of clinical variables including test results from serum-based markers before cancer is clinically diagnosed, and it maintains exclusive commercial access to a biobank of five million serum samples donated from more than 200,000 individuals over a 10-year period. Abcodia holds strategic collaborations with leading global organizations including Cancer Research UK, University College London and other academic and industry partners.
Abcodia is a privately held company funded through investments from Albion Ventures, Cambridge Innovation Capital, Scottish Equity Partners and UCL Business. Headquartered in Cambridge, U.K., the Company has operations in Boston, Mass. and a clinical laboratory in Memphis, Tenn. For more information, visit http://www.abcodia.com/.
About the ROCA® Test
Abcodia's first product, the ROCA Test indicates a woman's likelihood of having ovarian cancer. The ROCA Test is intended for postmenopausal women aged between 50 and 85, or for certain women between 35 and 85 years of age who are considered to have a higher risk due to family history of ovarian or breast cancer or genetic mutations in, for example, the BRCA1 or BRCA2 genes. The ROCA test has been evaluated as part of a multimodal screening strategy in several prospective clinical trials in both the U.K. and U.S. involving more than 215,000 women over the past 15 years. The results of those studies show that the ROCA Test, when used with appropriate transvaginal ultrasound as the follow up test, has a higher performance than other currently available methods that have been evaluated prospectively in healthy women. In the clinical studies, the ROCA Test detects the majority of ovarian cancer cases before the first signs or symptoms of ovarian cancer appear.
The ROCA Test is CE marked and is currently available in the private healthcare market in the U.K. The ROCA Test became available as a service from Abcodia's testing laboratory, in select U.S. markets in December 2015, and it will become available in additional U.S. states throughout 2016. For more information, visit http://www.therocatest.co.uk or http://www.rocatest.com.
i. American Cancer Society. http://www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-survival-rates . Retrieved 11/5/15.
ii. Ovarian Cancer Research Fund: http://www.ocrf.org/about-ovarian-cancer/treatment-of-ovarian-cancer/staging-and-grading/stage-iv . Retrieved 11/5/15.
iii. Menon U, Ryan A, Kalsi J, et al. Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening. J Clin Oncol. 2015;33(18):2062-71