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Six Weeks of Fluoroquinolone Antibiotic Therapy for Patients with Elevated Serum PSA is not Clinically Beneficial: A Randomized Controlled Clinical Trial: Beyond the Abstract

Prostate-specific antigen (PSA) levels are frequently utilized in an attempt to screen for prostate cancer despite known false positive rates between 10-20%. 1-3 Serum PSA may be affected by any prostatic disease, inflammation, or recent manipulation.  As a result of the low specificity of serum PSA, physicians are frequently faced with the dilemma of whom to biopsy; especially as trans-rectal ultrasound guided biopsy of the prostate is a potentially morbid procedure, with infection rates of approximately 3% after biopsy .4

There have been many efforts of improve the utility of PSA as a screening tool including: PSA velocity, PSA density, age-specific PSA, and fractionated PSA. Our results demonstrate that giving antibiotics in an effort to determine if the psa elevation is related to infection, is not supported as an option, despite its widespread use.  Newer clinical tools, including blood tests such as the Prostate Health Index (PHI) or the 4Kscore have been demonstrated to significantly improve clinical specificity for prostate cancer detection relative to PSA. The PHI is a blood test that combines PSA, free PSA, and pro-PSA and has been found to double the sensitivity of PSA analysis alone and is now listed as a marker of specificity for prostate cancer in the NCCN guidelines.6-7  The 4Kscore (a combination of total PSA, free PSA, intact PSA, human kallikrein 2, patient age, digital rectal exam and prior biopsy status) accurately predicts the risk of biopsy-detectable high-grade cancer and may inform care decisions when considering whether to proceed with a biopsy.8-10

Many physicians continue to prescribe an extended course of antibiotics in asymptomatic men with an elevated PSA despite the numerous new methods available to improve PSA specificity and the lack of convincing evidence supporting this practice. Administration of empiric pre-biopsy antibiotics to treat possible subclinical prostatitis is not a benign practice. The widespread use of antibiotics in asymptomatic men increases antimicrobial resistance, making treatment of true infections more difficult. In fact, the prevalence of fluoroquinolone-resistant bacterial strains is rising, with up to 24.4% of men being found to have resistant strains isolated after trans-rectal ultrasound biopsy.11 Additionally, the administration of fluoroquinolone antibiotics are not without their own risks and in addition to having an extensive drug-interaction profile, have been reported to cause dementia in the elderly and increase the risk of tendon rupture with prolonged use. 

As previously discussed, there are numerous studies examining antbiotic therapy to treat potential subclinical prostatitis, including several small randomized trials, with differing conclusions.  Whereas some studies state that serum PSA can be reduced with a course of antibiotics,12-13  other studies state that treating patients with antibiotics does not lower serum PSA levels.14-18 

Our report on a large single-institution prospective randomized trial of 150 men is unique compared to the aforementioned studies in that patients continued routine follow-up for an average of 4.6 years with routine PSA, exam, and ultrasound guided prostate biopsy per clinical practice guidelines. To some extent, this protects at some of the short-term variability of psa monitoring.  Overall, 90 patients (68%) underwent prostate needle biopsy with 38 (62%) of the treatment arm and 52 (72%) of the observation group undergoing biopsy. Positive biopsy results were equivalent in both the treatment and observation arm (63% and 52%, respectively), indicating that there is no evidence that the risk of prostate cancer would be reduced after antibiotic therapy. 

Our study has several limitations, most importantly that not every patient enrolled in the trial underwent subsequent biopsy, although it was recommended. Additionally, although post-hoc  analysis supports the statistical validation of the study, there was limited pre-study power analysis.  As stated above, we attempted to minimize these limitations with long-term longitudinal follow-up.    

Written by: Alyssa Greiman1 and Stephen Savage 1

1 Department of Urology, Medical University of South Carolina, Charleston SC

References:

  1. Kilpelainen TP, Tammela TL, Roobol M et al. False-positive screening results in the European randomized study of screening for prostate cancer. Eur J Cancer. 2011; 47 (18): 2698-705.
  2. Croswell JM, Kramer BS, Kreimer AR, et al. Cumulative incidence of false-positive results in repeated, multimodal cancer screening. Ann Fam Med. 2009; 7: 212-222
  3. Kilpelainen TP, Tammela TL, Maattanen L, et al. False-positive screening results in the finnish prostate cancer screening trial. Br J Cancer 2010; 102: 469-474
  4. Fluoroquinolone resistance in the rectal carriage of men in an active surveillance cohort: longitudinal analysis. Cohen JE, Landis P, Trock BJ, et al. J Urol. 2015 193 (2): 552-6
  5. Auffenberg GB, Ghani KR. Six weeks of fluoroquinolone antibiotic therapy for patients with elevated serum prostate-specific antigen is not clinicall beneficial: a randomized controlled clinical trial [Editorial Comment]. Urology. 2016. 
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  17. Baltaci S, Suer S, Halilog Lu AH, et al. Effectiveness of antibiotics given to asymptomatic men for increased prostate specific antigen. J Urol 2009; 191: 129-13
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