Raised CA 125

This blog post covers important points about CA125 which are taken from a recently published TOG article in January 2021. CA125 has been used as a tumor marker for ovarian cancer but with some limitations. 

I hope this quick post is helpful. 

Feel free to leave your feedback in comments and suggestions to improve future posts are welcome.

Thanks

Introduction

• Leading cause of death from any gynae malignancy → Ovarian Cancer
• Over 70% present with late stage disease (Stage III or IV)
• Normal Level CA 125→ <35 IU/ml
• Level can increase in both physiological or pathological conditions
• CA125 expressed in tissues derived from embryonic coelomic epithelia which includes endometrium, mullerian epithelium, peritoneum, pleura & pericardium
• CA125 has role in cell-mediated immunity
• Antigen is not produced directly by tumour & not a tumour marker per se

CA125 & mechanical stress

• Highest levels of CA125 seen in ascites associated with ovarian cancer
• CA125 correlates positively with ascites volume
• Levels are much higher in ascitic fluid than blood levels which shows that antigen originates in ascitic fluid rather than tumour itself

Ovarian Cancer & CA125

Use in Diagnosis

• CA125 increased in epithelial ovarian cancers & less commonly in non-epithelial
• Used with TVS to calculate RMI which guides further management
• If RMI >250 iu/ml → Refer to Cancer Centre
• 50% with stage I & occult cancers have normal levels

Use in follow-up

• After surgical resection→ serum levels fall by half within 10 days
• Post-op levels correlate with residual tumour mass & predictive for survival
• Median time for CA125 normalisation
• Complete remission → 1.5 months Partial remission→ 4 months
• 40% having normal CA125 found to have micro /macroscopic disease on 2nd look surgery
• Follow-up with CA125→ individualised 

Increased CA125 without ovarian cancer

• CA125 has poor sensitivity & specificity
• Elevated in only 75-90% with advanced disease

CA125 & menstrual cycle

• Levels fluctuate across cycle
• Peaks→ during menstruation Steady decline until end of cycle
• CA125 linked to endometrium & production associated with estrogen-dominated cell growth & activity
• Although levels high but still remain within normal limits

CA125 & pregnancy

• Levels altered
• Rise in first trimester (production by decidua) decline from start of 2nd trimester
• May increase with complications like pre-eclampsia
• Check only if clinically indicated & interpret with care

CA125 & endometriosis

• Clear link present
• Stage II & beyond levels may reach hundreds
• Predictive of pelvic adhesions

CA125 & benign conditions

Ref: TOG

CA125 in everyday clinical practice

CA125 in primary care

• NICE recommends to test all women who present with symptoms of ovarian cancer esp if ≥50 yrs

Symptoms Bloating  Early satiety ± reduction in appetite  Pelvic ± abdominal pain  Increased urinary urgency or frequency

Red Flag Symptoms Unexplained weight loss  Unexplained fatigue  Unexplained change in bowel habit  New onset symptoms of irritable bowel syndrome in women >50 y

If >35 IU/ml→ perform abdomino-pelvic ultrasound

• CA125 in primary care→ high specificity to identify ovarian & primary peritoneal cancer
• If cut-off reduced→ increases sensitivity but reduces specificity

CA125 & ovarian cysts

• Premenopausal Testing not recommended for simple cyst
• Postmenopausal With >1cm must have CA125 tested

Outside Clinical guidance

• If no obvious cause of elevated CA125 found→ thorough history, clinical examination, MDT approach & check CA19-9 & CEA
• Further imaging to be decided by MDT which may include CT chest, abdomen & pelvis and diagnostic laparoscopy

Unintended consequences

• Inappropriate testing may result in unnecessary investigations & invasive t/m
• May have psychological impact of cancer screening

Conclusion

• CA125 not sufficiently sensitive nor specific to diagnose on its own
• No reduction in mortality

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