By: Dan Sperling, MD
The entry point into the prostate cancer diagnostic pathway is usually the common PSA blood test. PSA, or prostate specific antigen, is a protein manufactured only by prostate cells, and small amounts of the protein are released into the circulatory system. Thus, a blood test can be used to measure the amount of PSA. Since the mid-1990s, this inexpensive test has been in use to screen for a higher-than-normal PSA, or one that is rising over a series of annual tests. One problem with this system is that there is no satisfactory definition for “normal” because various conditions appear to stimulate the release of greater PSA levels:
- Digital rectal exam (DRE)
- Benign prostatic hyperplasia (BPH or prostate enlargement due to aging)
- Prostate cancer
- Physical activity
- Sexual activity/orgasm
Even activities such as riding a bicycle or working a night shift[i] have been suggested as causes of elevated PSA. Two recent studies provide excellent examples of research into fact and fiction about elevated PSA values.
On the side of fact, a clinical study out of Johns Hopkins explores the connection between noncancerous (benign) inflammation of the prostate and an elevated PSA value.[ii] The authors point out that when a rise in PSA triggers a prostate biopsy, the tissue specimens evidence of inflammation, not cancer, but the connection between prostate inflammation and PSA has not been reported in detail.
The team identified 224 men in the placebo group of the Prostate Cancer Prevention Trial (PCPT) with normal digital rectal exams and PSA <4 ng/mL. Per study protocol, all had a prostate biopsy at the end of the study. By analyzing the needle samples for signs of inflammation, including the percentage of inflamed tissue area, its intensity and tissue compartment, the researchers correlated inflammation with PSA values (while adjusting for age at biopsy). They concluded that in men with no suspicion of prostate cancer, higher PSA was associated with greater inflammation in any type of prostate tissue. This type of finding underscores the value of pre-biopsy multiparametric MRI (mpMRI), since inflammation and other benign prostate conditions can be identified as a source of elevated PSA in the absence of detectable prostate cancer, and put a patient’s mind at ease.
What about bicycle riding as a source of a higher PSA? Fact or fiction? Perhaps the jury is still out, as suggested by a review of published clinical literature on the subject. A Canadian team conducted an extensive search of articles in medical and sports journal databases.[iii] They included studies in which PSA was measured in relation to cycling in healthy men with no known prostate condition. They identified eight studies that fit their criteria, totaling 912 men, with cycling activity ranging from 15 minutes per day to a 4-day biking event. The results were mixed. Two studies reported increases from baseline total PSA by as much as 3.3-fold; one study noted a small range of increase in free PSA while four studies found no change; and one study that compared PSA in professional vs. non-cyclists reported no difference between the two groups. Finally, data from six studies was collectively analyzed with the results that no significant increase in PSA was associated with pre- and post-cycling measures. The authors write, “Our findings suggest that there is no effect of cycling on PSA,” but caution that the scarcity of available studies and small average sample size may have been insufficient for meaningful statistics. Nevertheless, men whose baseline PSA becomes elevated after cycling may be comforted knowing that waiting for a couple of months and being re-tested after several days of no cycling will likely have reassuring results.
[ii] Umbehr MH, Gurel B, Murtola TJ et al. Intraprostatic inflammation is positively associated with serum PSA in men with PSA <4?ng?ml-1, normal DRE and negative for prostate cancer. Prostate Cancer Prostatic Dis. 2015 May 5. doi: 10.1038/pcan.2015.19. [Epub ahead of print]
[iii] Jiandani D, Randhawa A, Brown RE et al. The effect of bicycling on PSA levels: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2015 May 5. doi: 10.1038/pcan.2015.16. [Epub ahead of print]