prostate cancer ( pca ) is a frequent cancer that can be cured if early diagnosed ( 1 ) .
prostate specific antigen ( psa ) has become an important tool in pca screening ( 2 , 3 ) and men with serum psa greater than 4ng / ml are at higher risk of pca .
these patients are usually referred for a prostate biopsy ( bxp ) . however , increased psa levels are also associated with conditions other than cancer ( 3 ) , such as benign prostatic hyperplasia ( bph ) and prostatitis ( 4 , 5 ) .
chronic abacterial prostatitis is a common diagnosis in men of all ages , with widespread demographics , and it is a common reason for yearly visits to the doctor in the united states ( 3 ) .
only a few studies have linked prostatitis to an increase in serum psa ( 6 - 9 ) .
subclinical inflammation of the prostate could elevate serum psa in asymptomatic patients , confounding the use of psa values to indicate bxp ( 10 ) . in the majority of cases , prostatitis is an incidental pathological finding that has no clinical relevance
. there has been investigation into ways to decrease the misleading diagnosis resulting from inflammation .
repeat psa measurements after a period of observation in asymptomatic men can help to avoid unnecessary bxp ( 10 - 12 ) .
it has been suggested that antibiotic therapy ( at ) can also avoid bxp in many patients with prostate inflammation , in the psa grey zone ( 4.0 to 10.0ng / ml ) ( 6 , 13 , 14 ) .
currently , the indications of re - bxp in patients with a negative initial biopsy are few ; therefore , the first bxp must be precise . in an effort to improve the reliability of psa reduction as an indicator , and
consequently avoid unnecessary prostate biopsy , we conducted a prospective , controlled , non - randomized study to evaluate the effect of at on psa levels in patients who have an initially mild psa elevation ( 4.0 - 10ng / ml ) .
a prospective , controlled , non - randomized trial was carried out , with 106 asymptomatic men with total psa ( tpsa ) levels between 4.0 and 10.0ng / ml , who underwent routine evaluation from april 2007 to october 2011 .
the criteria for inclusion in the trial were digital rectal examination ( dre ) with no suspicion of malignancy and no history of urologic instrumentation , use of antibiotics , and urinary infection or sexually transmitted disease in the previous 12 months .
patients with diseases like diabetes or alcoholism , those describing the use of illegal drugs , those undergoing treatment for bladder outlet obstruction and patients with previous bxp ( positive and negative ) were excluded , as were those participants who did not use the at correctly or who did not carry out the follow - up correctly .
after institutional review board ( ethical committee ) approval , all study participants provided informed written consent before enrolment .
after the initial consultation , the serum levels of total psa ( tpsa ) and free psa ( fpsa ) were determined . the body mass index ( bmi ) , free psa fraction ( % fpsa ) , and psa density ( dpsa )
the participants were divided into two groups ( figure-1 ) according to their decision regarding the use of antibiotics .
this decision was made after the authors explained about the lack of evidence for this treatment .
group i patients received antibiotics , while group ii patients chose not to use at .
in group i , 64 men used ciprofloxacin 500 mg twice a day for a period of three weeks .
then , three weeks after the end of at , the serum psa , dpsa , and fpsa were again determined ( figure-1 ) .
the results of these patients were compared with those of 42 participants with psa between 4.0 and 10.0ng / ml whose exams were repeated after 6 weeks , without antibiotics , at the participant s discretion .
psa was considered to be normalized after treatment when the values returned to lower than 4ng / dl .
all of the participants underwent bxp 2 - 4 weeks after the second psa determination . based on the pre- ( psapre ) and post - treatment ( psapost ) psa values , the variation ( psavar )
thus , the variation rate ( psavar ) can be calculated with psa = ( psavar / psapre).100% . the bxp was ultrasound - guided and a minimum of 12 cores were sampled with determination of prostate volume in cubic centimetres ( cc ) . for those participants whose biopsy did not show pca ,
dre : digital rectal examination ; tpsa : psa total ; fpsa : psa free . 
 
the data obtained were analysed by testing the difference between two proportions for incidence of pca in each group , and evaluation of the decrease in psa levels . the other data were evaluated using the student t test , citing the critical t for a significance level of 0.05 .
the data obtained were analysed by testing the difference between two proportions for incidence of pca in each group , and evaluation of the decrease in psa levels . the other data were evaluated using the student t test , citing the critical t for a significance level of 0.05 .
the age of the participants ranged from 47 to 78 years , with a mean age of 66.1 years and median age of 61.8 years .
the mean age of g1 was 61.8 years and of g2 was 62.6 years ( p=0.60 ) .
the prostate volume was 51.123.8 gr in g1 and 53.919.2 gr in g2 ( p=0.52 ) .
the diagnosis of pca was confirmed in 25 of the 106 participants ( 23.6% ) ; in 9 out of 42 participants in g2 ( 21.4% ) and in 16 out of 64 in g1 ( 25% ) ( z=0.42 ; p>0.05 ) . 

group igroup iipwith atb meansdwithout atb meansdage ( years)61.817.8362.576.370.6bmi ( kg / m)27.863.5129.668.090.02volume ( cc)51.1523.8753.9719.280.527psapre6.821.666.761.680.429psapost5.291.85.382.160.409fpsapre1.250.471.310.400.233fpsapost1.030.441.060.480.383dpsapre0.150.050.140.060.261dpsapost0.110.060.110.070.369values expressed in mean  standard variation .
student t test there was a more than 10% psa decrease in 72 out of 106 patients ( 67.9% ) ; this rate was 65.6% and 71% in groups 1 and 2 , respectively ( z=-0.63 ; p>0.05 ) .
of the 42 participants from g1 in which the psa decreased after at , 6 ( 14.3% ) had a positive and 36 ( 85.7% ) a negative biopsy . in g2
, 30 participants had a psa reduction , with 4 ( 13.3% ) with a positive and 26 ( 86.7% ) a negative biopsy .
after the use of at , the psa level decreased to < 4ng / ml in 26 participants ( 24.5% ) ; in 15 ( 23.4% ) of those who used at , and in 11 ( 26% ) from g2 ( z=-0.032 ; p>0.05 ) .
the percentage of participants who had a value below 2.5ng / ml in the second psa was 9.4% for g1 , and 7.1% for g2 ( z=0.40 ; p>0.05 ) .
the initial and final values for psa , fpsa , % fpsa and dpsa decreased significantly in both groups ( table-2 ) . 

table 2comparison of initial and final psa values between groups.group igroup ii  pre - atbpost - atbppsa initialpsa finalptpsa6.821.665.291.8<0.0016.761.685.382.16<0.0001fpsa1.250.471.030.440.00021.310.41.060.480.0003%fpsa18.265.0820.136.350.001719.915.5621.086.950.072dpsa0.150.050.110.06<0.00010.140.040.110.070.0003values expressed in meanstandard variation .
student t test the mean total psa in g1 was 6.821.66 and 5.291.8ng / ml before and after treatment , respectively ( p<0.001 ) ; this represents a psavar of -1.531.93ng / ml . in g2 , the mean psa before and after antibiotics was 6.761.68 and 5.382.16ng / ml , respectively , with a psavar of -1.381.87 ( p<0.001 ) .
the psa in g1 was 25.56 , and in g2 was 28.7 ( p=0.429 ) .
the differences between g1 and g2 are shown in table-2 , according to the initial and final fpsa and dpsa .
there was no statistical difference between these values . in relation to dpsa , for g1
, the initial mean was 0.150.05ng / ml / gr of prostate , which decreased to 0.110.06ng / ml / gr ( p<0.0001 ) . in g2 , these figures were 0.140.04ng / ml / gr and 0.110.07ng / ml / gr , respectively ( p=0.0003 ) .
these same comparisons , analysing the cases with and without pca , are shown in table-3 . in the participants diagnosed with pca
, there was no statistical difference in relation to variation in psa , fpsa , % fpsa or dpsa .
however , in the participants with negative bxp , there was a significant reduction in psa , fpsa and dpsa , but not in % fpsa . 

table 3comparison of psa values between patients with and without prostate cancer.benignprostate cancer  psa initialpsa finalppsa initialpsa finalptpsa6.851.724.961.980.0016.631.496.521.190.2fpsa1.350.441.060.470.0011.020.370.970.400.077%fpsa19.965.0522.205.890.12415.524.7515.015.690.641psad0.140.060.100.06<0.000010.150.020.150.070.61values expressed in meanstandard variation .
student t test the sensitivity to a decrease greater than 10% in psa after the use of at to a diagnosis of prostate cancer was 31% , with a specificity of 23% ; the positive predictive value ( ppv ) was 12% and the negative predictive value ( npv ) was 23% .
regarding to the possibility of reducing unnecessary bxp after at , it should be emphasized that none of the 25 participants with pca had a final psa below 4ng / ml .
the present study analysed the effect of at on psa ( tpsa , fpsa , % fpsa and dpsa ) and investigated whether a relevant psa reduction induced by at could be related to a decreased cancer detection rate at biopsy .
physiological conditions other than cancer can cause an increase in serum psa levels that lead to potentially unnecessary biopsy procedures , increasing inconvenience for the patient , and causing over - diagnosis , over - treatment and elevated medical costs ( 15 ) .
prostate cancer is determined in only 34% of biopsies performed on the basis of psa elevation ( 1 ) , and in 20 - 30% in patients with normal dre and psa values of between 4 and 10ng / ml .
therefore , there is a high level of unnecessary biopsies , particularly in this group ( 16 , 17 ) .
the literature demonstrates a relationship between acute and chronic inflammation with elevated psa , but there have been recent studies that suggest the effects and benefits of chronic prostatitis treatment on psa ( 18 - 21 ) . in our study ,
pca was diagnosed more frequently in patients treated with at ( 25% versus 21.4% , p>0.05 ) , but without statistical relevance .
scardino ( 22 ) suggested that the changes in psa with at were similar to the random variations found in healthy men . also , potts ( 23 ) demonstrated no significant differences in bacterial cultures before or after at between psa responders and non - responders .
okada ( 24 ) and schatteman ( 25 ) concluded that subclinical inflammation could cause psa elevation , and emphasized the fact that nearly half of all clinically asymptomatic men with elevated psa levels have laboratory signs of prostatitis .
they suggest that the use of antibiotics would result in a decrease in psa levels in almost 50% of patients , thereby avoiding bxp .
this approach , however , requires careful follow - up , especially for patients whose psa levels fail to decrease to within the normal range ( 26 , 27 ) .
kaygisiz ( 1 ) and del rosso ( 19 ) suggested that at should be administered for 3 weeks , regardless of the presence of inflammation when psa levels are in the grey zone , before making a decision regarding whether or not to carry out a biopsy . on the other hand , serretta et al .
( 28 ) found no cancer present if psa levels decreased to below 4ng / ml , or more than 70% , and postulated that biopsy can be postponed , with only a small risk of failing to detect cancer . in multivariate analysis with other clinical variables ,
although this was not a randomized trial , it was prospective , assessing asymptomatic males without a clinical indication of prostatitis ; the study demonstrated that a large reduction in psa following antibiotics may help to avoid biopsy in selected patients in whom the psa elevation is probably due to inflammation / infection .
our data show that those patients who received at and those who did not had the same rate of normalization of psa ( < 4ng / ml ) .
, psa returned to normal levels in 23.4% of patients , compared with 26% patients in the non - treatment group .
the reason for this is still unclear , although psa normalization does not rule out pca diagnosis , and biopsy must still be considered .
magri et al . ( 29 ) , showed that the presence of bph may prevent the reduction of psa induced by combination pharmacological therapy , and suggest that care must be taken in the adoption of psa as a marker of therapeutic efficacy in the presence of confounding factors like bph .
according to these authors , psa should be used as a significant component of a strategy that integrates multiple diagnostic approaches .
( 11 ) showed a psa reduction in 63% of patients following at , with psa returning to normal values in 9% of cases , thus avoiding prostate biopsy .
( 23 ) documented psa normalization in 42% of patients , and brett et al .
these studies did not perform bxp in all patients to exclude the diagnosis of pca after treatment .
however , our study performed biopsy in all patients ( treated and not - treated ) , comparing the pca incidence between groups .
however , the entry of participants was not random , but based on the decision made by each participant ; this may represent a selection bias .
moreover , the shared decision with the patient is one of the commonalities in international guidelines .
approximately 10 - 15% of men will have a psa level > 4ng / ml in any given round of screening .
however , the level will return to normal in the subsequent test in 26 - 37% , and will become normal with the next testing in 40 - 55% .
( 31 ) showed that psa levels tend to fall when repeated after 45 days , regardless of at .
once normalized , 65 - 83% of men have normal psa levels for several years without therapy ( 32 ) .
if psa levels do not fall , the probability of finding cancer is higher than if levels decrease .
this occurs because pca is more likely to occur in men with sustained psa elevation than in those with a randomly variable psa that is temporarily elevated ( 24 ) .
our study shows a lower , but not significant , cancer detection rate in patients with decreased psa , fpsa and dpsa after antibiotic therapy , demonstrating a correlation between psa normalization and prostatitis or negative biopsy .
a psa reduction rate of 10% occurred in 58.5% of patients ; however , it was lower in patients who received antibiotics than in those who received no treatment ( 65.6% versus 71% ) , but there was not significant difference ( p>0.05 ) .
the sensitivity , specificity and accuracy of a psa reduction rate of 10% were 31% , 23% and 25% , respectively .
this level is therefore not recommended as a cut - off point for clinical decision - making .
( 28 ) showed a significantly lower cancer detection rate in patients with decreased psa after antibiotic therapy , demonstrating a correlation between psa reduction and negative biopsy , with an odds ratio varying from 1.2 to 3.9 for reduction percentages of between 10 and 90% .
they suggested that a psa reduction rate of 50% can be adopted and 11% of biopsies avoided until a further psa increase occurs .
( 33 ) reported that the f / t psa ratio appears to be more suggestive of pca than psa in these cases .
it should be emphasized , however , that a long follow - up time is needed to determine whether any of these men will have prostate cancer in the near future , and wider studies are required to identify the optimal psa reduction level at which biopsy can be postponed .
( 35 ) claimed that bph and prostatitis appear to be more frequent causes of psa elevation .
scardino ( 22 ) recommended that asymptomatic men presenting with a modestly elevated psa level ( < 10ng / ml ) and a normal digital rectal examination could be reassured and then the psa level could be repeated once or twice ; if the levels remained elevated , this would be an indication of the need to perform a biopsy .
( 36 ) , in a prospective randomized and double - blind trial with placebo , demonstrated that psa reduction occurred after antibiotic and placebo application , and suggested that a decrease in psa does not indicate the absence of pca .
recently , faydaci et al . ( 37 ) demonstrated that at given to patients with psa levels higher than the threshold value has not led to a significant change in prostate needle biopsy decisions , and suggested that bxp should be considered without the use of at in patients with high psa values if a suspicion of prostatitis does not exist .
the literature does not support the evidence that antibiotics alter psa levels except in the presence of bacterial prostatitis , which is an uncommon condition .
we should wait for a second psa assessment before prostate biopsy in asymptomatic male patients once the psa will spontaneously reduce in a quarter of cases ; and that antibiotic use has no role in this clinic scenario ( 36 ) .
there are several implications in the use of empiric at for patients with elevated psa levels .
scardino ( 22 ) emphasized some disadvantages of this approach , such as cost , toxicity , and the fact that it can cause complications of infection .
moreover , a decrease in psa after at does not absolutely exclude the presence of pca , even if the psa decreases to very low levels .
in addition , there is concern that the indiscriminate use of empiric antibiotics could lead to the development of resistant bacterial species and thereby expose the patient to more resistant and aggressive sepsis , should a biopsy eventually be performed ( 38 - 40 ) .
empirical antibiotic therapy in asymptomatic male patients is not related to psa reduction and that psa reduction after antibiotic can not postpone prostate biopsy . based in our findings
additionally , it is not possible to define a safe rate reduction and further studies stratifying the relative values of reduction and cancer risk are needed .
 purpose we investigated the effect of antibiotics on psa in asymptomatic patients with mild psa elevation.materials and methods we prospectively evaluated , in a non - randomized design , 106 asymptomatic patients with psa of 4 - 10ng / ml , with a negative digital rectal examination and with no urinary tract infection evidence for 2 years . patients were divided into two groups : those treated with antibiotics for 3 weeks ( g1 ) and those who were not treated ( g2 ) . 
 psa was taken six weeks after and prostate biopsy was performed in all patients.results pca was diagnosed in 25 of 106 patients ( 23.6% ) : 16 ( 25.0% ) in g1 and 9 ( 21.4% ) in g2 ( p>0.05 ) . 
 psa normalization was experienced in 24.5% . in g1 
 , psa returned to < 4ng / ml in 15 ( 23.4% ) patients compared to 11 ( 26% ) patients in g2 . in the patients with a positive biopsy , no significant variation was noted in psa , fpsa , % fpsa and dpsa after antibiotic treatment . 
 a significantly lower cancer detection rate was noted with decreased psa , fpsa , and dpsa after antibiotic use 
 . a psa reduction rate of 10% occurred in 58.5% , and this was similar in both g1 and g2 groups . 
 the sensibility , specificity and accuracy of psa reduction of 10% were 31% , 23% and 25% , respectively.conclusion empirical antibiotic therapy in asymptomatic male patients is not related to psa reduction . 
 the greater than 10% psa reduction after antibiotic in this population can not postpone prostate biopsy . 
INTRODUCTION
MATERIAL AND METHODS
Statistical analysis
RESULTS
DISCUSSION
CONCLUSIONS