Role of Tumour Markers in Cancer Diagnosis

The only tumour markers cited in the NICE Urgent Cancer Referral Guidance that should be requested  in Primary Care to support diagnosis of possible cancers are Ca-125 and PSA.

CA-125

CA-125 is elevated in 80% of patients with advanced ovarian cancer.

May also be elevated in pancreatic, gastric, colonic, and breast carcinoma and nonmalignant conditions such as benign cysts, endometriosis, pelvic inflammatory disease, ascites and in menstruation and pregnancy.

May be normal in 50% of early stage ovarian cancer.

Prostate-specific antigen (PSA)

• PSA is a serine protease which is usually specifically expressed by both normal and malignant prostate cells
• Useful to detect cancer at an early stage or before symptoms develop resulting in early treatment of the cancer
• PSA values are likely to be increased with age and in conditions such as benign enlargement of the prostate, prostatitis and lower urinary tract infections
• Elevation of serum PSA is more a sensitive and specific indicator of prostatic carcinoma than prostatic acid phosphatase (PAP)
• PSA is raised in over 90% of cases when carcinoma is first detected by comparison to 50% for PAP.
• PSA lacks the required specificity to be a test for prostatic cancer as it is also increased in most patients with benign prostatic hypertrophy.

Detection of Recurrence of Malignant Disease

There are many tumour markers; but their most valuable application of tumour markers has been in the detection of recurrence of malignant disease following treatment.

Examples include :

Hormones: Calcitonin – medullary thyroid carcinoma

Enzymes:

• Prostatic acid phosphatase (PSA) – spread of prostatic carcinoma
• Bone alkaline phosphatase – primary and secondary osteoblastic tumours eg osteogenic sarcoma; (significantly, not multiple myeloma)

Tumour Antigens:

Carcinoembryonic antigen (CEA) – post-operative colorectal carcinoma; lacks the specificity or sensitivity to establish a diagnosis of cancer

Alpha-feto protein (AFP) – hepatocellular carcinoma, teratoma

Monoclonal antibodies raised to carbohydrate or glycoprotein antigenic determinants:

• CA 125 – ovarian carcinoma
• CA 15-3 – breast carcinoma
• CA 19-9 – pancreatic, gastric, hepatobiliary carcinoma