Sunday, December 20, 2015

Part 2: Using the Risk of Ovarian Cancer Algorithm - UKCTOCS Study Mortality Results

In Part 1 I discussed the Risk of Ovarian Cancer Algorithm screening test and its release in five states in the US.

On December 17th,  Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial was published in the Lancet journal. This was an answer to my question regarding improved survival for those women screened using the ROCA/ CA-125. 

Details:, number NCT00058032
Randomized Trial: 202,638 Post menopausal women 50-74  from England, Wales, Northern Ireland
Three arms:  
1. Annual Multimodal Screening (MMS) using CA-125 and risk algorithm ( 50,624 women ). I call this arm the ROCA test but will use MMS when discussing the study.
2. Annual transvaginal ultrasound (TVU) (50,623 women)  
3. No screening ( 101,299 women) .  The distribution ratio was 1:1:2.

OC was diagnosed in 1282 women of all women
630 cases in the unscreened women with 347 deaths
338 cases in the screened with CA-125 and ROCA 148 deaths 
314 cases in the ultrasound screen group and 154 death. 

One analysis showed less deaths in the MMS and TVU groups but the difference was not significant.
Mortality reduction using the Cox Model for years 0-14 showed a 15% reduction in deaths in the MMS group versus the control group. And there was an  11% reduction in mortality in the TVU group versus the control group. Graphs of the control versus MMS and control vs TVU are the same up to about 10 years. If you look at specific time periods there is a change in mortality reduction. For MMS the 0-7 time period showed an 8% reduction vs control and for 7-14 year time period  there was a 23% reduction in mortality versus the control. 

A second analysis which removed women,who had ovarian cancer before the screening of the trial began and who died early on in the study ( "prevalent cases" in which the change point in the CA-125 occurred before enrollment in the study) found that the MMS group had an average of 20% less deaths for the entire study ( 0-14 years) .

You may view watch this video ( 2hours 40 minutes) of the UKCTOCS Ovarian Cancer Mortality Results Meeting ( includes psychosocial evaluations of participants as well as mortality data ):

During this video it was stated that these early results from the UKCTOCS ( no significant p value)  is similar to the results of the late effect seen in the PSA European study( for prostate cancer) and time is needed to follow-up and confirm late effects. 

Discussion of the results:
There were media articles ( NYT)  written stating that early detection of ovarian cancer was now possible because of this test. 

Medpage- Ovarian Cancer Screening Study Falls Short 

A press release from Abcodia may be found here.

Ovarian organizations commented on the results : 

"While we join the researchers in their optimistic outlook and are hopeful that more positive results will be released in the future, today we must acknowledge that the results do not show that screening works."

“These initial results are promising for the ovarian cancer community, but there is much more data analysis needed in the coming months to determine the true impact on the future of early detection testing for ovarian cancer. We are looking forward to discussions with the community in the coming months to understand how ROCA may fit into the prevention of ovarian cancer."

For me questions still remain.
What was the grade of the women that died during the study?  I know from the previous JCO article that 82% of the  women in the study diagnosed with Ovarian Cancer were high grade. How did that correlate with those who died. 

From the JCO article 41 % of the women dx with OC in the MMS arm were stage 1 or 2. How does that relate to their mortality?

What I wish I knew:
Does the ROCA / CA-125 test work on women earlier than age 50? Those that are pre-menopausal?

If you were able to look at the BRCA status of the women in the study would that effect the results? (Is the test better on those with a BRCA mutation?

As many others during the past few days have said. This is promising but more work needs to be done. 

Every day is a blessing!
updated 12/21/2015

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