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Permits to Avoid Or Postpone Prostate Biopsy in Selected Patients Prostate Cancer and Prostatic Diseases (2008) 11, 148–152 & 2008 Nature Publishing Group All rights reserved 1365-7852/08 $30.00 www.nature.com/pcan ORIGINAL ARTICLE PSA reduction (after antibiotics) permits to avoid or postpone prostate biopsy in selected patients V Serretta1, A Catanese1, G Daricello1, R Liotta1, R Allegro2, A Martorana3, F Aragona3 and D Melloni1 1Department of Internal Medicine, Cardiovascular and Nephro-Urological Diseases, Institute of Urology, University of Palermo, Palermo, Italy; 2Department of Statistics, GSTU (Gruppo Studi Tumori Urologici) Foundation, Palermo, Italy and 3Department of Human Pathology, University of Palermo, Palermo, Italy Microscopic foci of prostatitis may induce prostate-specific antigen (PSA) increase. PSA reduction after antibiotics might identify those patients in whom biopsy can be avoided. Ninety-nine patients received ciprofloxacin for 3 weeks, of whom 59 showed PSA reduction. Histology detected small foci of prostatitis in 65% of cases. Carcinoma was found in 40 and 20.3% of patients with unchanged or decreased PSA, respectively (P ¼ 0.03). No cancer was detected if PSA decreased below 4 ng/ml or more than 70%. Biopsy can be postponed, with a low risk of missing a cancer, if PSA decreases more than 70% or below 4 ng/ml. Prostate Cancer and Prostatic Diseases (2008) 11, 148–152; doi:10.1038/sj.pcan.4500996; published online 17 July 2007 Keywords: prostate cancer; prostatitis; antibiotics; PSA; transrectal biopsy Introduction biopsy. The aim of our study was to investigate the possibility of reducing the number of prostate biopsies in Disruption of the natural anatomic and physiologic patients showing PSA decrease or normalization after barriers between the prostatic milieu and the blood- antibiotic therapy. This approach could be useful in stream is an important factor determining increased patients for whom it is necessary to postpone biopsy and serum prostate-specific antigen (PSA) levels. Inflamma- in patients, with previous negative biopsies, willing to tion alters prostatic duct integrity causing PSA leakage avoid biopsy until further PSA increase. A secondary from the acini and ductal lumina. In 1989, Dalton was the aim was to identify the level of PSA reduction that must first to report total PSA elevation in acute prostatitis.1 be reached to avoid biopsy, limiting as much as possible Many experimental and clinical studies suggest a the risk of missing a cancer. correlation between acute and chronic prostatitis and increased serum PSA levels.2–6 Subclinical inflammation of the prostate could elevate serum PSA in asymptomatic Patients and methods patients without clinically detectable prostate cancer. 7 Ninety-nine asymptomatic Caucasian men requiring Gerstenbluth et al., in 2002, reported chronic prostatitis urological consultation for PSA between 4 and 10 ng/ as a common finding in radical prostatectomy speci- dl, with negative rectal examination for cancer and mens. In the majority of cases, prostatitis is an incidental candidate to biopsy, were entered in our study. Exclusion pathological finding that causes no clinical symptoms. criteria were abnormal mid-void urine, urinary tract These patients are categorized by the National Institutes infection, urinary symptoms, clinical signs or documen- of Health (NIH) into category IV prostatitis (asympto- ted history of prostatitis. The patients should have at matic inflammatory prostatitis) (Supplementary Infor- least two previous elevated PSA detections, showing no mation). It has been suggested that repeating the decrease greater than 10%, to confirm the possibility of measurement of PSA in symptomatic men can help 8,9 spontaneous PSA reduction. All patients were submitted avoid unnecessary prostatic biopsy. Although prosta- to physical examination and rectal exam before biopsy. titis may cause PSA elevation, asymptomatic patients are Prostate gland enlargement was a common finding, but not routinely screened for this disease before transrectal there was no single objective finding indicative of prostate cancer or prostatitis. Since our patients were asymptomatic, they did not undergo prostate massage Correspondence: Professor V Serretta, Department of Internal and laboratory-specific analyses to rule out prostatitis. Medicine, Cardiovascular and Nephro-Urological Diseases, Institute Written informed consent was obtained from all patients. of Urology, University of Palermo, Via Pietro Calandra 12, int 25 90148 Basal total-PSA (t-PSA) and free-PSA (f-PSA) determina- Tommaso Natale, Palermo, Italy. E-mail: [email protected] tions were repeated in all patients at study entry. Received 23 March 2007; revised 4 May 2007; accepted 5 June 2007; Eighteen patients (18.2%), with repeated PSA values published online 17 July 2007 between 10.2 and 20 ng/dl, were accepted in the study as PSA reduction after antibiotics V Serretta et al 149 they needed to temporarily postpone the biopsy. These Table 1 The characteristics of the 99 patients at entry patients were informed of the increased risk of prostate tumour. Ciprofloxacin (500 mg b.i.d.) was given orally for Patients’ characteristics Mean s.d. Median Range 3 weeks. t-PSA and f-PSA determinations were repeated Age (years) 65 6.7 65 48–83 2 weeks after therapy. Independently from the value PSA (ng/ml) 8.1 3.2 7.3 4.1–20.0 of the repeated PSA, 2–4 weeks after therapy cessation, PSA 4–10 (ng/ml), 81 patients 6.9 1.8 6.7 4.1–10.0 all patients were submitted to transrectal ultrasound- PSA 10, 2–20 (ng/ml), 18 patients 13.7 2.6 13.1 10.2–20.0 guided biopsy (biplanar mode, B&K sonograph). Free PSA 1.3 1.4 1.0 0.1–7.4 f-PSA/t -PSA ratio 0.15 0.10 0.14 0.01–0.49 Prostate volume was estimated assuming an ellipsoid Prostate volume (cm3) 37.8 15.5 37.0 19.0–82.0 shape. It was evaluated only at the time of the trans- rectal biopsy, and no attempt to study volume variations, Abbreviation: f-PSA/t-PSA ratio, free/total-PSA ratio. presumably of small entity, caused by antibiotic therapy was done. Ultrasound-guided transrectal biopsy, using an 18-G needle fitted to an automatic biopsy gun, was Table 2 Effect of antibiotic therapy on t-PSA and f-PSA/t-PSA performed. The number of cores varied from 12 to 21 ratio according to patients’ age, prostate volume, number of PSA after antibiotic therapy Mean s.d. Median Range previous biopsies and presence of suspicious area detected by ultrasound. In particular, 12 prostate cores PSA (ng/ml) 7.03 2.79 6.60 1.00–19.27 were obtained in 61 patients, 14–16 cores in 25 patients Free PSA 1.19 0.75 1.02 0.09–3.57 owing to suspicious area at ultrasound and 21 cores f-PSA/t-PSA ratio 0.17 0.09 0.16 0.01–0.38 in 13 patients with previous negative biopsy or with PSA reduction (ng/ml) 2.87 2.93 2.00 0.18–13.80 3 PSA reduction (%) 28.07 21.36 22.22 2.37–91.39 prostate volume between 60 and 82 cm . Local anaes- PSA ratio f/t variation 0.06 0.14 0.06 À0.38 to 0.34 thesia with transrectal infiltration of 5 ml of 20% mepivacaine solution, through a 20-G needle at the Cancer detection rates Patients % Cancer % junction between each seminal vesicle and the prostate, was performed. Routine haematoxylin–eosin-stained Unchanged/increased PSA 40 40.4 16 40 slides were obtained and were routinely examined to Decreased PSA 59 59.6 12 20.3 PSA reduction 470% 5 5.1 00 avoid any deviation from the usual clinical practice. PSA reduction 450% 13 13.1 2 2 In addition, a pathological systematic analysis of the 4pbasal PSAp10 ng/ml 6 6.1 00 specimens was performed to score the inflammation 10obasal PSAp20 ng/ml 7 7.1 2 2 that was graded using a four-point scale according to PSAo4 ng/ml 8 8.1 00 6 the system formulated by Irani: grade 0, no inflamma- Abbreviation: f-PSA/t-PSA ratio, free/total-PSA ratio. tory cells; grade 1, scattered inflammatory cell infiltrate Bold values indicate no prostate cancer detected. within the stroma without lymphoid nodules; grade 2, non-confluent lymphoid nodules; and grade 3, confluent infiltrate of mononuclear inflammatory cells. Fifty-nine patients (59.6%) showed t-PSA reduction Patients with PSA reduction and negative biopsy will after therapy. In eight of them (8.1%), PSA decreased be followed with PSA determinations and digital rectal below 4 ng/ml. The mean and median PSA reduction exam (DRE) at 6-month intervals for the first year and rates were 28 and 22%, respectively. The reduction of then yearly. t-PSA had a widespread variation ranging between 2.4 and 91.4%. The median absolute reduction was 2.0 ng/ml, up to 13.8 ng/ml. PSA ratio remained almost Statistics unchanged, with a median value of 0.16 and a median Statistical analysis was performed by regression analysis. rate of change of 6%, as f-PSA varied according to t-PSA. The univariate associations between tumour absence At statistical analysis, comparing the baseline character- at biopsy with patients’ age, basal t-PSA and f-PSA, istics of patients with and without t-PSA reduction after t-PSA and f-PSA reduction after therapy were examined antibiotics, the former had a significantly higher baseline and differences assessed by w2 and Fisher’s exact tests. PSA value (median value 9.0 vs 5.0 ng/ml; Po0.0001). Statistical comparisons of the groups were performed On the other hand, no difference emerged in terms of using the Mann–Whitney U test and the Kruskal–Wallis age, prostate volume, f-PSA/t-PSA ratio, numbers of non-parametric analyses of variance.
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