What’s new in prostate cancer screening and prevention?
ABSTRACTProstate cancer is extremely common but causes death in only a minority of men in whom it develops, facts that raise issues regarding screening and treatment morbidity. Two large trials of screening with prostate-specific antigen (PSA) measurements came to seemingly opposite conclusions. Furthermore, a large trial of selenium and vitamin E found that these agents have no value as preventive agents.
KEY POINTS
- An elevated PSA level lacks specificity as a test for prostate cancer, but PSA measurements can be useful in combination with clinical risk factors or to measure changes in PSA over time.
- Rather than relying on PSA screening alone, we should stratify the risk of prostate cancer on the basis of race, age, PSA level, family history, findings on digital rectal examination, whether the patient has ever undergone a prostate biopsy, and whether the patient is taking finasteride (Proscar). A simple online tool is available to do this.
- There is no PSA level below which the risk of cancer is zero.
- Finasteride has been found in a randomized trial to decrease the risk of prostate cancer, but vitamin E and selenium supplements have failed to show a benefit.
Genetic tests: Not yet
Some data suggest that we can use genetic tests to screen for prostate cancer, but the tests are not yet as good as we would like.
Zheng et al16 reported that 16 singlenucleotide polymorphisms (SNPs) in five chromosomal regions plus a family history of prostate cancer have a cumulative association with prostate cancer: men who had any five or more of these SNPs had a risk of prostate cancer nearly 10 times as high as men without any of them. However, the number of men who actually fall into this category is so low that routine use in the general population is not cost-effective; it may, however, be useful in men with a family history of prostate cancer.
Other SNPs have been linked to prostate cancer (reviewed by Witte17). Having any one of these loci increases one’s risk only modestly, however. Only about 2% of the population has five or more of these SNPS, and the sensitivity is about only about 16%.
A commercially available DNA test (Decode Genetics, Reykjavik, Iceland) can detect eight variants that, according to the company, account for about half of all cases of prostate cancer.
Prostate cancer screening: My interpretation
I believe the two new studies of PSA screening suggest there is a modest benefit from screening in terms of preventing deaths from prostate cancer. But I also believe we should be more judicious in recommending treatment for men whom we know have biologically indolent tumors, although we cannot yet identify them perfectly.
In the past, we used an arbitrary PSA cutoff to detect prostate cancer of any grade, and men with high levels were advised to have a biopsy. Currently, we use continuous-risk models to look for any cancer and biologically significant cancers. These involve nomograms, a risk calculator, and new markers.
We use the PCPT risk calculator routinely in our practice. I recommend—completely arbitrarily—that a man undergo biopsy if he has a 10% or higher risk of high-grade cancer, but not if the risk is less. I believe this is more accurate than a simple PSA cutoff value.
CAN WE PREVENT PROSTATE CANCER?
Prostate cancer is a significant public health risk, with 186,000 new cases and 26,000 deaths yearly. Its risk factors (age, race, and genes) are not modifiable. The benefit of screening in terms of preventing deaths is not as good as we would like, and therapy is associated with morbidity. That leaves prevention as a potential way to reduce the morbidity and perhaps mortality of prostate cancer and its therapy.
Epidemiologic studies suggest that certain lifestyle factors may increase the risk, ie, consumption of fat, red meat, fried foods, and dairy; high calcium intake; smoking; total calories; and body size. Other factors may decrease the risk: plant-based foods and vegetables, especially lycopene-containing foods such as tomatoes, cruciferous vegetables, soy, and legumes, specific nutrients such as carotenoids, lycopene, total antioxidants, fish oil (omega-3 fatty acids), and moderate to vigorous exercise. However, there have been few randomized trials to determine if any of these agents are beneficial.
