Ovarian cancer screening disappoints, but lessons remain

Ovar­i­an can­cer is often described as a “silent killer”. The symp­toms, such as bloat­ing, are vague and eas­i­ly con­fused with those of non-life-threat­en­ing con­di­tions like irri­ta­ble bow­el syn­drome. 

About 4,000 women in the UK die from ovar­i­an can­cer every year, accord­ing to Can­cer Research UK. There is cur­rent­ly no nation­al screen­ing pro­gramme for detect­ing the dis­ease, which main­ly affects post-menopausal indi­vid­u­als.

Researchers hoped they could change that, sav­ing thou­sands of lives. In 2001, the UK Col­lab­o­ra­tive Tri­al of Ovar­i­an Can­cer Screen­ing (UKCTOCS) began fol­low­ing more than 200,000 women aged between 50 and 74 from the gen­er­al pop­u­la­tion. Par­tic­i­pants were screened annu­al­ly with either an ultra­sound of their ovaries or a blood test, along­side a con­trol group that did not under­go any screen­ing. 

The results were heav­i­ly antic­i­pat­ed. How­ev­er, in May the large-scale tri­al found that screen­ing failed to reduce deaths from ovar­i­an can­cer. 

“With this dis­ease, there is so much need,” says lead inves­ti­ga­tor Pro­fes­sor Usha Menon from the MRC Clin­i­cal Tri­als Unit at UCL, who has been work­ing to improve ovar­i­an can­cer detec­tion since the mid-1990s. “We thought this might be the solu­tion that would change things. But we were dis­ap­point­ed.” 

That means there won’t be a rec­om­men­da­tion for rou­tine screen­ing. Still, experts say there are plen­ty of lessons to take from the study.

To screen or not to screen

Around 90% of women diag­nosed with ovar­i­an can­cer at the ear­li­est stage sur­vive for five years or longer. But if the dis­ease is detect­ed at the lat­est stage, this fig­ure plum­mets to just 13%. Almost six in 10 cas­es are diag­nosed at a late stage. 

Screen­ing is designed to spot can­cers as ear­ly as pos­si­ble, when treat­ment is most like­ly to be suc­cess­ful. But a screen­ing pro­gramme will only be approved for use in the NHS if it’s known to save lives. The test also needs to reli­ably detect can­cer or abnor­mal changes that could lead to the ill­ness, as well as being cost-effec­tive and accept­able so peo­ple will actu­al­ly take it. 

There is good evi­dence that all of this is true for the UK’s exist­ing ear­ly detec­tion pro­grammes for bow­el, cer­vi­cal and breast can­cers. For ovar­i­an can­cer, how­ev­er, the goal has yet to be achieved. 

“For all the lives a future screen­ing pro­gramme might save, there are going to be quite a few women who have surgery for what turns out not to have been can­cer,” explains con­sul­tant gynae­col­o­gist Dr Adam Rosen­thal from UCLH. “You can’t intro­duce gen­er­al pop­u­la­tion screen­ing with all the down­sides until you’re real­ly cer­tain it is sav­ing a sub­stan­tial num­ber of lives.”

Although UKCTOCS didn’t show a sur­vival ben­e­fit, there were some hope­ful find­ings. While annu­al ultra­sounds couldn’t detect can­cer ear­li­er or save lives, researchers were able to find some ovar­i­an can­cers ear­li­er than nor­mal in women who under­went reg­u­lar blood tests. 

The test, which tracked lev­els of a chem­i­cal called CA125 that is released from ovar­i­an tumours, picked up 39% more can­cers at an ear­ly stage com­pared to the no screen­ing group. As CA125 lev­els can vary between women, the researchers devel­oped an algo­rithm that mea­sured how someone’s lev­els changed over time. If their lev­els of CA125 rose dur­ing the tri­al, they were referred for an ultra­sound scan.

Even a slight­ly ear­li­er diag­no­sis can make a big dif­fer­ence to ovar­i­an can­cer patients in terms of treat­ment options and qual­i­ty of life, says Tra­cie Miles, gynae­co­log­i­cal can­cer infor­ma­tion nurse at The Eve Appeal. Detect­ing the dis­ease at an ear­ly stage could mean less intense treat­ment with few­er hos­pi­tal trips – and more time with loved ones.

Next steps for ovarian cancer research

So why didn’t ear­ly diag­no­sis save lives? It’s still a mys­tery to the researchers. Menon says it could be that screen­ing did not pick up enough of these ear­ly can­cers, or that they need to be detect­ed even ear­li­er to affect sur­vival rates. 

How­ev­er, it’s pos­si­ble that the blood test used in the UKCTOCS tri­al might help women who are at high risk of devel­op­ing the dis­ease. Some women have a gene that makes them sig­nif­i­cant­ly more prone to ovar­i­an can­cer. Rosen­thal found that by screen­ing these women every few months, it might be pos­si­ble to diag­nose the dis­ease before it reach­es an advanced stage. 

Reg­u­lar sur­veil­lance could give them a dam­age-lim­i­ta­tion option until they’re ready to have a pre­ven­ta­tive oper­a­tion to remove their tubes and ovaries. How­ev­er, Rosen­thal stress­es the blood test is not an alter­na­tive to surgery, which is the only way of pre­vent­ing ovar­i­an can­cer.

While the UKCTOCS results are dis­ap­point­ing, some experts laud the study as an extra­or­di­nary piece of research that will help sci­en­tists design future clin­i­cal tri­als. “Tri­als don’t always find the results that we hope for,” says Sophia Lowes, health infor­ma­tion man­ag­er at Can­cer Research UK. “But the results of UKCTOCS also clear­ly demon­strate how cru­cial it is to do long-term stud­ies like this, because it’s the only way to know whether screen­ing can save lives.”

And the research could live on. Women who took part in the study gave their per­mis­sion for oth­er researchers to use their data and blood sam­ples, cre­at­ing a rich data­base that might help sci­en­tists deter­mine whether new tests for ear­ly diag­no­sis per­form bet­ter than those used in the study. 

Researchers could also look for dif­fer­ent chem­i­cals in the blood that could sug­gest ovar­i­an can­cer. And the infor­ma­tion might even help fur­ther our under­stand­ing of how ovar­i­an can­cer devel­ops in the first place. 

What’s more, as the women in UKCTOCS were fol­lowed for so long, some were diag­nosed with oth­er can­cers. Their data and sam­ples will also help researchers who are work­ing on ear­ly detec­tion of oth­er forms of the dis­ease, such as lung, breast and bow­el can­cer. 

It’s cer­tain­ly not the end of the road for ear­ly detec­tion in can­cer care, says Lowes. The NHS is cur­rent­ly tri­alling anoth­er blood test, or “liq­uid biop­sy”, devel­oped by biotech com­pa­ny Grail to see if it can detect dif­fi­cult-to-diag­nose can­cers (such as ovar­i­an and pan­cre­at­ic) in patients with­out symp­toms. The health ser­vice hopes the test could increase the pro­por­tion of can­cers that are caught ear­ly, one of the major goals of the NHS’s long-term strat­e­gy.

But until such meth­ods show promise, most women with ovar­i­an can­cer will con­tin­ue to be diag­nosed after they go to their GP with symp­toms. “It is real­ly impor­tant that the results of UKCTOCS do not dis­cour­age the test­ing of women with rel­e­vant symp­toms,” says Dr Garth Fun­ston from the Uni­ver­si­ty of Cam­bridge, who stud­ies the role that pri­ma­ry care plays in the ear­ly detec­tion of can­cers. 

“It is key that as well as work­ing towards devel­op­ing an effec­tive screen­ing pro­gramme, we work to devel­op new approach­es to ensure that women with symp­toms are diag­nosed and can receive treat­ment in a time­ly way.” 

It’s still impor­tant to raise aware­ness of pos­si­ble symp­toms, which will play a cru­cial role in reduc­ing deaths from ovar­i­an can­cer. Miles urges women – espe­cial­ly those aged over 50 – who are expe­ri­enc­ing per­sis­tent bloat­ing, unex­plained bow­el changes or abdom­i­nal pain or swelling to get it checked out. She also advis­es any­one with a fam­i­ly his­to­ry of ovar­i­an can­cer to speak to a doc­tor, who might then arrange a genet­ic test. 

“I don’t think ovar­i­an can­cer is the silent killer,” she says. “I think it whis­pers. We’ve just got to work out how to lis­ten to it.”