Fluctuations In PSA And The Use Of Antibiotics

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Men's health;  Primary Care / General Practice
Article Date: 07 Aug 2008 - 4:00 PDT

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UroToday.com - A two to four week course of antibiotic therapy is often used in patients with an elevated PSA to exclude inflammation as an etiology of the elevated level. This talk reviews the data regarding variations in PSA, etiology and the practice of antibiotic use.

Fluctuations in PSA are anticipated as the concentration of PSA in prostatic fluid is approximately a million fold higher than in serum. To begin with, there are both lot-to-lot differences in PSA assays - as well as method-to-method differences between the methodologies used. As such, it's prudent to have a patient get their PSA measurements at the same laboratory on a consistent basis to avoid this variation. If one looks at the variation of the PSA test over a two week period there is a 15% coefficient of variation in the total PSA, a 17% variation in the pre PSA and a 14% free PSA variation. The median PSA, as reported by Catalona, for men in their forties is 0.7ng/ml, for men in their fifties 0.9ng/ml, for men in their sixties 1.3ng/ml, and for men in their seventies 1.7ng/ml. Eastham reported on year to year fluctuations in PSA. He found that 26 to 37% of men with increased PSA had a level return to normal on the next annual evaluation. Forty-five to 55% of men with increased PSA had the level return to normal within four years. In 65 to 83% of those men, it remained normal for years afterwards. For those who had a prostate biopsy recommended for abnormal PSA levels 40 to 53% would have had their PSA parameters fall below the biopsy criteria during the four years of follow-up. The suggestion is that more than one PSA should be used to confirm an abnormal PSA level prior to a biopsy.

There are also seasonal variations in the PSA. The French arm of the European randomized study screening for prostate cancer showed there were significantly higher PSA concentrations in summer than in other seasons. This resulted in a 23% increase in the likely hood of being referred for prostate biopsy during the summer season. Finasteride can also affect the PSA level. Finasteride will decrease both the total and free PSA by approximately 50%. As such, the free to total PSA ratio remains unchanged. This suggests that an abnormal decrease in the free to total ratio could potentially be due to cancer rather than Finasteride therapy. Furthermore, the use of one milligram per day of Finasteride for alopecia results in a 40% PSA decrease in men ages 40 to 49 and a 50% decrease in men ages 50 to 59. The herbal remedy saw palmetto has not been shown to alter PSA levels in a large double blind randomized multicenter trial.

Antibiotic therapy for an elevated PSA has the theoretical advantage of treating infection, providing cost effective therapy by avoiding prostate biopsies and decreasing patient inconvenience and morbidity from the biopsy. The disadvantages include unnecessary antibiotic expense, potential side effects and adverse reactions and an increase in multidrug resistant organisms. In chronic prostatitis, it has been shown that the total PSA, free PSA and pro-PSA are all significantly higher in patients with infection. A 28 day course of fluoroquinolone therapy in patients with chronic bacterial prostatitis resulted in a median PSA decrease from 8.3 to 5.3ng/ml as reported by Dr. Schaeffer. In 42% of patients with a PSA greater than 4ng/ml the PSA decreased to less than 4ng/ml after antibiotics. Dr. Catalona is evaluating the role for PSA velocity in men with an elevated PSA with regard to inflammation as an etiology. He points out that the traditional PSA velocity cut off for prostate biopsy is 0.75ng/ml/year in men with a PSA above 4 and for men with a PSA less than 4ng/ml a cut off of 0.3 to 0.5ng/ml/year should be used. If you look at the cancer detection rate by PSA velocity in patients treated with antibiotics 36% of his preliminary cohort had a negative PSA velocity of whom about one-third of those undergoing biopsy were found to have cancer. In those who had an unchanged or positive PSA velocity following an antibiotic treatment all had a biopsy and the majority were found to have cancer. This was a small preliminary cohort which is undergoing further evaluation. He points out that a decrease in PSA does not rule out prostate cancer and a lack of decrease of PSA does rule in cancer. The point being, that repeated PSA measurements provide more valid information for patient management and he does believe that an empirical course of antibiotics is a reasonable measure performing prostate biopsy.

It is very important to appreciate that there is increasing drug resistance as reported by Dr. Richard Macchia at the AUA New York Section meeting in 2007. They found that the incidence of fluoroquinolone resistance in 2.6% of patients in the year 2006 compared to 0.8% in 2005 and 0.6% in 2004. Ecoli, the most common organism responsible for bacteria prostatitis in men undergoing prostate biopsy was found in 91% of patients who had a positive urine culture or infective complications following prostate biopsy and 86% of these were resistant to fluoroquinolones

The rationale and evidence-based recommendations for management of an elevated PSA would include repeat confirmation of a newly elevated PSA without the use of antibiotics as an initial test. Patients should be counseled not to ejaculate for forty-eight hours prior to the repeat PSA test. The test should be standardized in the same laboratory, and a urinalysis, and if indicated urine culture performed. An expressed prostatic secretion with >20 WBC/HPF should be considered prostatitis and sent for culture and potentially treated with antibiotics. Significant fluctuations in PSA should raise the suspicion of inflammation or infection as an etiology and in these patients it remains controversial; however, this would be the population of patients to consider a short course of two weeks of antibiotics. This remains a nonevidence based practice, which needs to be individualized to the patient. Using PSA velocity in a short and longer-term fashion may be a way to stratify patients for the need for prostate biopsy. Those who undergo a course of fluoroquinolone antibiotics should not have a prostate biopsy within one month of completing the antibiotics to allow the colonic flora to reestablish itself to a normal state.

References:

Eastham JA et al JAMA 289 2695-2700, 2003
Ornstern DK et al J. Urol 157 219-228, 1997
Schaeffer AJ et al J. Urol 174 161-164, 2005

Presented by: Michelle Ramirez, DO, and Christopher P. Evans, MD, at the Masters in Urology Meeting - July 31, 2008 - August 2, 2008, Elbow Beach Resort, Bermuda

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