Ups and downs in PSA readings- an excellent review

[Guest guest]

The long abstract below is from a presentation at a current urology

conference in Vail Colorado. It is a good summary of issues confounding

interpretation of rises (and declines) in PSA readings, reinforcing the

advice that one should not get too excited about short-term changes in

PSA.

The Best to You and Yours!

Jon

WUF 2008 - Fluctuations in PSA and the Use of Antibiotics

Saturday, 02 February 2008

VAIL, CO (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. 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.

by:

, DO

J. Catalona, MD

P. , MD

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 P. , MD, at the 32nd Winter Urologic Forum

- State-of-the-Art in Urology - January 25-29, 2008 - Vail, Colorado,

USA