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An ideal tumour marker should allow the screening, the follow-up and then the best treatment of cancer. For these purposes, it should

• be sensitive and specific,
• reflect the tumour load,
• predict prognosis,
• predict relapse.

Sensitivity and specificity

Sensibility is defined as the proportion of patients who have a positive marker.

Specificity is defined as the proportion of healthy people with a normal marker. A marker should have a high sensibility and specificity rate.

In the above example, the sensibility is 90% and the specificity also 90%. However it is clear that an elevated marker does not necessarily mean cancer! Throughout the use of a marker to screen a tumour, we can notice that it is not really specific and that many other pathologies may provoke its modification.

Thus, a very sensitive and very specific marker cannot be used for early detection. For a frequent cancer (incidence 1/10,000), 1,000 subjects would have a wrongly elevated marker and unnecessary biopsies.

However, a marker which is very specific for an organ, like PSA for the prostate, might be an interesting marker: although the increase in its level may be related to other prostate diseases, and the other clinical situations may be sufficiently different to enable their 'diagnosis' (for example, prostatitis and benign prostate hyperplasia are clinically quite different from cancer).

Schematic representation of the diagnosis delay in relation with PSA rising. PSA rises years before the clinical manifestation of the pathology. Since the doubling time of prostate cancer is relatively low, we can retroactively project the beginning of the disease. For instance, 10 years before the diagnosis of metastatic prostate cancer, the patient probably already had elevated PSA (in red) thus permitting its diagnosis before the appearance of metastases. The purple area is for localised cancer, blue for benign adenoma.

Another clear example is the level of HCG and AFP in testicular cancer.

After orchidectomy, all of the tumour tissue should have been removed. The isolated elevation of the tumour marker (HCG or β-HCG > 3 u and/or αFP > 3) signifies the persistence of cancer lesions in the patient's organism. An adjuvant chemotherapy should therefore be undertaken.

An opposite example is given by Ca-125, a tumour maker used following the surveillance of ovarian cancer, and which is not at all specific.

The following table shows the tissues for which immunochemistry is positive for Ca125 :

The next table shows the various pathologies (and physiological states) for which an increase in Ca-125 level may be observed exclusive of cancer.

Thus using Ca-125 is of no utility for screening ovarian cancer.

PSA, used with caution (see the screening chapter), might be the exception.