The medical literature abounds with examples of the benefits of early cancer detection. Cure rates are always dramatically higher before the tumor has spread and while surgery is still an option. For example in cervical cancer, detection at the earliest stages of the disease is associated with a 99% five-year survival rate. Similarly encouraging statistics may be found for cancers of the breast, ovaries, colon, skin, and other sites.
Cancer detected through physical examination or medical imaging is usually too advanced for hope of a cure, which has led to an explosion of research into molecular diagnostics. Immunoassays, the leading category of such tests, are exquisitely sensitive and have the potential to diagnose cancer at the stage of just a few cells. Unfortunately commercial molecular diagnostics for cancer suffer from a lack of specificity, sensitivity, and overall robustness.
An Ounce of Prevention
Cancer biomarker discovery has been hampered by the heterogeneity of the diseases known as cancer. Even within one cancer type, for example breast, several distinct clinical types exist; moreover, within these researchers have found dozens of genotypic differences. Despite these challenges, the search goes on for these important diagnostic tools.
Once cancer biomarkers are discovered and approved, their dissemination among medical specialists is relatively uncontrolled. Three cancer markers that immediately come to mind are prostate-specific antigen (PSA) for prostate cancer, CA-125 for ovarian malignancies, and HER2-neu in breast cancer.
PSA is found in normal prostate tissue and at elevated levels when the gland is inflamed. Since PSA is not specific to prostate malignancy, diagnosis of prostate cancer based on rising PSA serum levels results in a high rate of false positives—up to 75% according to some studies. False positives are highly undesirable because they trigger costly, invasive medical interventions that divert healthcare resources that could be better spent.
Biopsies of 100 suspected prostate cancer patients with PSA readings of 3 ng/mL or higher will return only 25 confirmed cases. In addition, 40% of PSA-negative readings are false. PSA was approved by the FDA at a time when prostate cancer diagnostics were essentially nonexistent. Were the PSA test to come up for regulatory review today, it is unlikely it would be approved for prostate cancer screening.
Diagnostic tests that are approved for one purpose are often applied to situations for which the test was not designed. PSA is a prime example. PSA was originally approved in 1985 as a test for the recurrence of prostate cancer in men who had been treated with radiation or surgery. Today the test is routinely prescribed as a screening tool despite the fact that evidence linking PSA testing to improved outcomes is lacking.
The U.S. Preventive Services Task Force concluded after reviewing the literature that it would take 1,000 PSA screenings to prevent one death from prostate cancer. At the same time the numerous false positives and inconclusive results would subject hundreds of these men to unnecessary interventions that include biopsies, surgery, and medical treatment, not to mention the anxiety of uncertainty regarding their health status.
Clearly a useful cancer test will possess high diagnostic specificity and sensitivity, be expressed exclusively by tumors of one type, and detect cancer early to provide a reasonable hope of cure. The ability to predict both outcomes and response to therapy could be considered added benefits.