Ovarian cancer: CA125 is no longer one number

Clinical Rounds, the GPAtlas podcast. Malignancy & Cancer. 19 minutes. Published 31 August 2026. Free to listen.

Clinical source: our own Ocean article "Ovarian Cancer", last reviewed 10 May 2026.

Transcript

Sarah: Hello, and welcome to GPAtlas Clinical Rounds. I'm Sarah, and this is the podcast where we take one thing you'll genuinely see this week, and work out together what to do about it.

Ben: And I'm Ben. I'm the one who's been through the guidance, so when Sarah tells you what she did, I'll tell you whether the evidence agrees with her. Today, a blood test whose threshold most of us are still carrying around wrong.

Sarah: So. Sixty-three year old woman, in with about four months of bloating and a change in her bowel habit. Bit of early fullness when she eats. Nothing dramatic. And the word that arrives in my head, and I suspect in yours, is irritable bowel. It fits, it's common, and it's reassuring. And in a woman of sixty-three, it is the single most dangerous thought I could have.

Ben: Three things. Why new bowel symptoms after fifty are a red flag rather than a diagnosis. The CA125 thresholds, which changed in April and are not one number any more. And the two findings that skip the blood test entirely.

Sarah: So, the symptoms first. Bloating that persists. Early satiety or losing your appetite. Pelvic or abdominal pain. And urinary urgency or frequency. Our article gives it as BEAT, which is a decent hook. And the qualifier that matters is persistence: more than twelve times a month is the marker. Not once, not occasionally. Twelve times a month is most days.

Ben: And here is the pitfall our article names outright, which I think is the most useful sentence in the whole topic. Labelling a woman aged fifty or over with new bloating and altered bowel habit as irritable bowel syndrome. IBS almost never presents for the first time at that age, so a confident benign label without testing is the classic way ovarian cancer is missed in primary care. In that group, the new symptom is itself the indication to test. So Sarah's instinct was the right instinct to notice and the wrong one to follow.

Sarah: New IBS-type symptoms in a woman over fifty are not IBS until you have proved it. The newness is the reason to test.

Ben: Now the number, or rather the numbers. NICE updated NG12 in April, and the old single threshold of thirty-five has gone, replaced by age-adjusted thresholds. And they do not simply fall with age, so it is worth having them properly. Forty to forty-nine, thirty- five or above. Fifty to fifty-nine, thirty-one. Sixty to sixty-nine, twenty-four. Seventy to seventy-nine, twenty-five. Eighty and over, thirty-one. So the threshold falls to a low point in the sixties, then comes back up.

Sarah: So for my sixty-three year old, the number I'm judging against is twenty-four, not thirty- five. And that is the whole point of the change. Under the old rule a CA125 of twenty- eight in this woman was normal, and I'd have reassured her. Under the new one it is above her threshold and she gets an urgent ultrasound. Same blood result, completely different afternoon.

Sarah: And there's a separate rule for younger women, which I nearly missed. At thirty-nine or under, you don't use CA125 in isolation at all. You consider an urgent direct-access ultrasound instead. And in the under-forties, if you do suspect an ovarian malignancy, add alpha-fetoprotein and beta-hCG, because germ cell tumours are the ones CA125 can miss.

Sarah: Thirty-five, thirty-one, twenty-four, twenty-five, thirty-one. And under forty, don't use it on its own.

Sarah: And the two things that mean you don't wait for a blood test at all. If you feel a pelvic or abdominal mass that isn't obviously fibroids, that is a suspected cancer pathway referral irrespective of the CA125. And ascites, shifting dullness or a fluid thrill, the same. The examination overrides the blood test. Which is a good reason to actually examine the abdomen of the woman you were about to call irritable bowel.

Ben: And the mirror image of that, which is the one that catches people going the other way. A normal CA125 never excludes ovarian cancer. It can be normal in early-stage disease and in mucinous tumours, and it is raised by endometriosis, fibroids, pelvic inflammatory disease, menstruation, pregnancy, ascites, heart failure and liver disease. It is a triage tool, not a screening test and not a diagnostic one. And if the CA125 is up, the ultrasound is normal, and you are still worried, our article is explicit: do not be falsely reassured. Reconsider the referral.

Sarah: A mass or ascites goes straight on the pathway. And a normal CA125 is not permission to stop worrying.

Sarah: Let's go back a step, because before the threshold question there's a harder one: who are you testing at all? The symptoms are famously vague, and the way our article makes them usable is a checklist called BEAT. B for bloating. E for eating difficulty or early satiety. A for abdominal or pelvic pain. And T for toilet, meaning urinary changes. Persistent or frequent, and it gives a countable rule: often more than twelve times a month, particularly aged fifty or over.

Sarah: And that frequency rule is what turns a vague complaint into a decision. Twelve times a month is roughly three times a week. So the question in the room stops being does this sound sinister, which is unanswerable, and becomes how many days a week does this happen, which she can actually tell you. Our article suggests a symptom diary for exactly that: recording the frequency and severity of the bloating, the satiety, the pain and the urinary symptoms, to assess against that trigger.

Ben: And there are red flags outside BEAT that should also lead you to test. Unexplained weight loss, fatigue, or a change in bowel habit in an older woman. Those don't feel gynaecological, which is precisely why they get worked up down other pathways for months.

Sarah: More than twelve times a month. Ask how many days a week.

Ben: Now the single most important rule in this whole episode, and it overrides the blood test entirely. Act on physical signs immediately. Ascites, or a pelvic or abdominal mass that isn't obviously fibroids, means a suspected-cancer pathway referral straight away, without waiting for a CA125 result. The test is a triage tool for the woman you can't examine your way to an answer on. If you can already feel the answer, the test only adds delay.

Sarah: And the corollary, which is the examination one. A normal abdominal examination does not exclude ovarian cancer. So you palpate for masses, distension, organomegaly and tenderness, and if it's normal that changes nothing about whether you test. It's also worth looking wider in the woman who looks unwell: cachexia, supraclavicular lymph nodes, and signs of a pleural effusion in advanced disease.

Ben: A mass or ascites goes straight to the pathway. Do not wait for the CA125.

Sarah: The classic miss, and I think every GP should hear this one said out loud once a year. Never diagnose new irritable bowel syndrome in a woman aged fifty or over without excluding ovarian cancer. Our article is direct about it: IBS almost never presents for the first time at this age, so a confident benign label without testing is the classic way ovarian cancer is missed in primary care. In that group the new symptom is itself the indication to test. You measure the CA125 and you examine her, rather than reaching for an antispasmodic.

Sarah: And I'd add the human reason it happens, because it isn't ignorance. A fifty-four year old with bloating and irregular bowels who is otherwise well is a genuinely reassuring consultation. She looks fine. She feels a bit silly for coming. And mebeverine is a kind, quick answer that makes everybody feel better for six weeks.

Ben: New IBS over fifty is not a diagnosis. It is a test request.

Ben: Then interpreting the result, which cuts both ways. CA125 can be normal in early-stage disease and in mucinous tumours. And it's raised in a long list of benign things: endometriosis, fibroids, pelvic inflammatory disease, menstruation, pregnancy, ascites, heart failure, liver disease. So it produces false alarms in younger women and false comfort in exactly the early-stage disease you were hoping to catch. Our article puts it in five words: a normal CA125 never excludes ovarian cancer.

Ben: And the sequence that catches people out most often is the next step. A normal ultrasound after a raised CA125 does not stop referral if clinical concern persists. Raised marker, normal scan, still worried, is not a reassuring combination. It's a reason to assess for other causes and reconsider referral, not to close the episode.

Sarah: And it's worth knowing what happens after you refer, because patients ask and because it helps you explain the wait. The ultrasound score, her menopausal status and the CA125 are combined into a risk of malignancy index, and a score of two hundred and fifty or above triggers referral to a specialist gynaecological oncology multidisciplinary team. So the number you sent isn't the decision. It's one of three inputs into it.

Ben: Raised marker, normal scan, still worried. That is not reassurance.

Sarah: Two parts of the history I used to skip. Ask about endometriosis, which is associated with the clear-cell and endometrioid subtypes. And explore the reproductive risk: nulliparity, early menarche, late menopause, prolonged oestrogen-only hormone replacement therapy. But note the protective side too, because it's a better conversation: combined oral contraceptive use, having children, and breastfeeding all reduce risk.

Ben: And family history, which has an actual referral route rather than a vague sense of worry. Refer to familial cancer or clinical genetics where there's a strong family history, or known BRCA1, BRCA2 or Lynch syndrome. BRCA testing is offered for high-grade serous histology. And for confirmed high-risk individuals, risk-reducing removal of the tubes and ovaries substantially reduces risk, though that's a specialist decision, with hormone replacement considered afterwards for a surgical menopause.

Sarah: And where she goes if it isn't ovarian, because a negative work-up shouldn't be a dead end. Persistent gastrointestinal symptoms with a negative ovarian work-up go to gastroenterology. A simple or benign cyst on the scan goes to routine gynaecology. Strong family history goes to genetics. Somebody owns the symptom at the end of it.

Ben: And three presentations that need acute action rather than a pathway: bowel obstruction, tense ascites causing breathlessness, and venous thromboembolism, because ovarian cancer is prothrombotic. A new DVT or PE in a woman with months of vague abdominal symptoms is a connection worth making at the time rather than in the review afterwards.

Sarah: And the two things I'd want said in the room. First, there is no national screening programme, and that's an evidence-based position rather than a gap: population screening, including the big UK trial using CA125 with or without ultrasound, has not shown a mortality benefit. Symptom-based detection is the approach, which is precisely why the twelve-times-a-month question carries so much weight.

Sarah: And second, the safety net, in her words rather than ours. A normal result is reassuring, but if your symptoms carry on or get worse, please come back. That sentence is the whole difference between a normal CA125 that closes a door and one that holds it open. And a note on who this applies to: these recommendations apply to women, and to trans men and non-binary people with female reproductive organs. Anyone with ovaries.

Ben: Normal today. Come back if it carries on. Say both halves.

Ben: Can I put a second patient in front of you, because I think she's the one who really tests this. Fifty-four, comes in with about three months of bloating and slightly looser bowels, no weight loss, examination completely normal, and she apologises twice for wasting your time. Nothing about her feels like cancer.

Sarah: And that is the entire problem, isn't it. She is the reassuring one. If she'd looked unwell I'd have scanned her that week.

Ben: So run her through what we've said. She's over fifty with new bowel and bloating symptoms, which our article says is almost never new IBS at that age, and the symptom itself is the indication to test. Her examination is normal, which excludes nothing. So she gets a CA125, measured against the threshold for her age band, and she gets examined properly rather than an antispasmodic and a follow-up if it doesn't settle.

Ben: And say her CA125 comes back at twenty-eight. Under the old single threshold of thirty- five that's normal and she goes home. Against her age-adjusted band it may not be. That is the whole reason the change happened, and she is the patient it was made for. Even then, if the symptoms carry on, a normal result does not close the door, because CA125 can be normal in early-stage and mucinous disease.

Sarah: The reassuring patient is the one the change was made for.

Ben: Right, exam corner. Sarah, and everybody driving, a few seconds. A fifty-five year old woman with three months of bloating and early satiety. You examine her and find no mass and no ascites. Her CA125 comes back at twenty-nine. What do you do? A, reassure her, it is below thirty-five. B, arrange an urgent direct-access ultrasound. C, refer on the suspected cancer pathway. Or D, treat as irritable bowel and review in six weeks.

Ben: It's B. She is fifty-five, so her threshold is thirty-one, and twenty-nine is below it. But the whole reason the bands exist is that you cannot judge her against thirty-five, and A is the old reflex. She stays symptomatic with a result that does not settle the question, so an urgent direct-access ultrasound is the next step. C would be right if you had felt a mass or found ascites, and then you would not have waited for the blood test at all. And D is the pitfall the episode opened with, in the exact age group where it does the most harm.

Sarah: So. Three things for Monday. One. New IBS-type symptoms in a woman over fifty are the indication to test, not a diagnosis. Two. CA125 has age bands now: thirty-five, thirty- one, twenty-four, twenty-five, thirty-one, and under forty you do not use it alone. And three. A mass or ascites goes on the pathway whatever the blood says, and a normal CA125 never excludes it.

Sarah: One thing to reflect on, if you're logging this. Think about the last woman over fifty you told had irritable bowel. Did you examine her abdomen, and did you send a CA125? The full transcript and the references are on the episode page. Ben and I are synthetic voices. The medicine isn't. See you next week.

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