prostate cancer ( pca ) is one of the most common cancers and the second most common cause of cancer - related death in men in the united states .
however , the age - adjusted incidence rate of pca in korea increased from 10.1 per 100,000 people in 2002 to 27.0 per 100,000 people in 2012 . according to the annual report of the national cancer center in 2012 , pca was the fifth most common cancer and the seventh most common cause of cancer - related death in korean men . to detect pca ,
the results of prostate biopsy may include pca , benign diagnosis ( e.g. , benign prostate hyperplasia [ bph ] , inflammation , and prostatitis ) , high - grade prostatic intraepithelial neoplasia ( hgpin ) , and atypical small acinar proliferation ( asap ) . in patients with a benign diagnosis
hgpin is defined as proliferation of the acini and ducts in epithelial cells similar to that of pca .
it has been reported that the cancer detection rate on second biopsy in patients with hgpin ranges from 25% to 79% .
asap is a term used by pathologists when the obtained tissue is not sufficient to be diagnosed with pca but exhibits abnormal morphology .
it has been reported that the cancer detection rate on second biopsy in patients with asap ranges from 21% to 60% .
hgpin and asap have been recognized as premalignant lesions and are potential risk factors for pca .
however , there is no consensus regarding the management of patients with hgpin and asap .
therefore , we compared the cancer detection rate , gleason scores on second biopsy , and unfavorable disease rate after radical prostatectomy ( rp ) in order to investigate the differences in patients with benign diagnosis , hgpin , and asap on first biopsy .
these results will provide important information for establishing the appropriate clinical management of korean patients with hgpin and asap .
this study was approved by the institutional review board of samsung medical center in seoul , korea ( irb no .
we retrospectively reviewed data from 7,477 patients who underwent prostate biopsy between march 1995 and november 2012 .
initial prostate biopsy was performed when the serum prostate - specific antigen ( psa ) level was more than 2.5 ng / ml and/or there were abnormal findings on the digital rectal examination .
patients who were diagnosed with pca on a first biopsy and those who did not undergo a second biopsy were excluded .
the second biopsy was done when the result of the first biopsy included hgpin and asap , and the psa level was continuously elevated .
finally , a total of 1,323 patients who underwent a second biopsy were enrolled in this study .
the patients were divided into three groups according to the results of the first biopsy : benign diagnosis , hgpin , and asap .
additionally , patients with hgpin or asap were subdivided into two groups according to the number of positive cores : single core of hgpin ( hgpin1 ) , multiple cores of hgpin ( hgpin2 ) , single core of asap ( asap1 ) , and multiple cores of asap ( asap2 ) .
clinicopathologic parameters such as age , prostate volume , psa level on first and second biopsy , and the time between the first and second biopsy were compared among the three groups .
psa density ( psad ) was calculated by using the formula of the psa level divided by the prostate volume on first biopsy .
psa velocity was also calculated by dividing the time between the first and second biopsy into the change in the psa level .
the cancer detection rate was compared and univariate and multivariate analyses were performed among the three groups to predict the diagnostic factors of pca on a second biopsy , including clinical factors , hgpin , and asap .
gleason scores and the rate of unfavorable disease were compared in patients who underwent rp .
unfavorable disease was defined as a gleason score8 , pathologic staget3b ( involving the seminal vesicle ) , and/or spread to the regional lymph nodes after rp .
we used an automatic biopsy gun with an 18-gauge needle to harvest the prostate tissue . to minimize hemorrhagic complications ,
patients were advised not to take any oral anticoagulants including aspirin for 7 days before the procedure .
laboratory studies including prothrombin time and activated partial thromboplastin time were checked routinely to confirm normal coagulation profile .
all patients received an intramuscular dose of aminoglycoside just before the procedure , and oral ciprofloxacin and/or cephalosporin for 7 days after the procedure .
sextant biopsy was the standard method before 2009 , which was later replaced by 12-core biopsies .
all procedures were performed on a hospital - affiliated outpatient clinic basis , and all patients provided informed consent prior to the procedure .
continuous and categorical variables were described as meanstandard deviation and absolute values ( percentage ) , respectively .
the distributions of clinicopathologic variables among the bph , hgpin , and asap groups were compared by using analysis of variance .
comparisons of gleason scores and subgroups of hgpin ( hgpin1 vs. hgpin2 ) or asap ( asap1 vs. asap2 ) were performed by using pearson chi - square test .
comparisons of the cancer detection rate , unfavorable disease rate , and predictors for pca were performed by using logistic regression .
. 20.0 ( ibm co. , armonk , ny , usa ) , and a two - tailed p - value < 0.05 was considered to be statistically significant .
this study was approved by the institutional review board of samsung medical center in seoul , korea ( irb no .
we retrospectively reviewed data from 7,477 patients who underwent prostate biopsy between march 1995 and november 2012 .
initial prostate biopsy was performed when the serum prostate - specific antigen ( psa ) level was more than 2.5 ng / ml and/or there were abnormal findings on the digital rectal examination .
patients who were diagnosed with pca on a first biopsy and those who did not undergo a second biopsy were excluded .
the second biopsy was done when the result of the first biopsy included hgpin and asap , and the psa level was continuously elevated .
finally , a total of 1,323 patients who underwent a second biopsy were enrolled in this study .
the patients were divided into three groups according to the results of the first biopsy : benign diagnosis , hgpin , and asap .
additionally , patients with hgpin or asap were subdivided into two groups according to the number of positive cores : single core of hgpin ( hgpin1 ) , multiple cores of hgpin ( hgpin2 ) , single core of asap ( asap1 ) , and multiple cores of asap ( asap2 ) .
clinicopathologic parameters such as age , prostate volume , psa level on first and second biopsy , and the time between the first and second biopsy were compared among the three groups .
psa density ( psad ) was calculated by using the formula of the psa level divided by the prostate volume on first biopsy .
psa velocity was also calculated by dividing the time between the first and second biopsy into the change in the psa level .
the cancer detection rate was compared and univariate and multivariate analyses were performed among the three groups to predict the diagnostic factors of pca on a second biopsy , including clinical factors , hgpin , and asap .
gleason scores and the rate of unfavorable disease were compared in patients who underwent rp .
unfavorable disease was defined as a gleason score8 , pathologic staget3b ( involving the seminal vesicle ) , and/or spread to the regional lymph nodes after rp .
we used an automatic biopsy gun with an 18-gauge needle to harvest the prostate tissue . to minimize hemorrhagic complications ,
patients were advised not to take any oral anticoagulants including aspirin for 7 days before the procedure .
laboratory studies including prothrombin time and activated partial thromboplastin time were checked routinely to confirm normal coagulation profile .
all patients received an intramuscular dose of aminoglycoside just before the procedure , and oral ciprofloxacin and/or cephalosporin for 7 days after the procedure .
sextant biopsy was the standard method before 2009 , which was later replaced by 12-core biopsies .
all procedures were performed on a hospital - affiliated outpatient clinic basis , and all patients provided informed consent prior to the procedure .
continuous and categorical variables were described as meanstandard deviation and absolute values ( percentage ) , respectively .
the distributions of clinicopathologic variables among the bph , hgpin , and asap groups were compared by using analysis of variance .
comparisons of gleason scores and subgroups of hgpin ( hgpin1 vs. hgpin2 ) or asap ( asap1 vs. asap2 ) were performed by using pearson chi - square test .
comparisons of the cancer detection rate , unfavorable disease rate , and predictors for pca were performed by using logistic regression .
all statistical analyses were performed by using ibm spss statistics ver . 20.0 ( ibm co. , armonk , ny , usa ) , and a two - tailed p - value < 0.05 was considered to be statistically significant .
the baseline characteristics of the patients according to the results of the first biopsy are summarized in table 1 .
a total of 1,323 patients were enrolled , and the patients ' mean age was 62.98.8 years .
the mean serum psa level was 7.315.7 ng / ml and the mean prostate volume was 41.319.8 mm on the first biopsy .
the mean psad was 0.20.3 ng / ml / ml and the mean psa velocity was 0.99.9 ng / ml / y .
patients with hgpin or asap were older than those with a benign diagnosis ( p<0.001 ) .
the mean time between the first and the second biopsy was shorter in patients with hgpin ( 7.5 months ) than in those with a benign diagnosis or asap ( 32.9 and 30.1 months , respectively , p<0.001 ) .
however , prostate volume , psa level on first and second biopsy , psad , and psa velocity did not differ significantly among the three groups ( each p>0.05 ) .
overall , 214 patients ( 16.2% ) were diagnosed with pca on the second biopsy ( table 2 ) .
pca was detected in 164 patients ( 14.6% ) with a benign diagnosis , in 33 patients ( 22.1% ) with hgpin , and in 17 patients ( 32.1% ) with asap .
the cancer detection rate was significantly higher in patients with hgpin and asap than those with a benign diagnosis ( hgpin vs. benign diagnosis , p=0.027 , and asap vs. benign diagnosis , p=0.004 , respectively ) .
however , there was no significant difference between the asap and hgpin groups ( p=0.150 ) . when patients were divided into subgroups according to the number of positive cores , pca was detected in 15 patients ( 16.7% ) with hgpin1 and in 18 patients ( 30.5% ) with hgpin2 ( table 3 ) .
patients with hgpin1 and those with a benign diagnosis had similar cancer detection rate ( 16.7% and 14.6% , p=0.567 , respectively ) . on the other hand , pca was detected in 13 patients ( 31.0% ) with asap1 and in 4 patients ( 36.4% ) with asap2 .
the cancer detection rate was not significantly different between patients with asap1 and asap2 ( p=0.732 ) .
however , patients with asap1 showed a much higher rate of cancer detection than in patients with a benign diagnosis ( 31.0% and 14.4% , respectively , p=0.003 ) .
the cancer detection rate was significantly higher in patients with hgpin2 and asap on first biopsy . in patients who were diagnosed with pca on second biopsy ,
the hgpin and asap groups had greater proportions of patients with a gleason score6 than did the benign diagnosis group ( 57.6% , 70.6% , and 51.8% , respectively ) and lower proportions of patients with a gleason score8 than did the benign diagnosis group ( 6.1% , 5.9% , and 16.5% , respectively ) .
however , there were no statistically significant differences in gleason scores among the three groups ( p=0.324 ) . in patients diagnosed with pca
unfavorable disease was detected in 8 patients ( 8.3% ) with benign diagnosis , 2 patients ( 8.0% ) with hgpin , and 1 patient ( 10.0% ) with asap .
however , there were no meaningful differences in the unfavorable disease rate ( benign diagnosis vs hgpin , p=0.857 , and benign diagnosis vs asap , p=0.957 respectively ) ( table 5 ) .
table 6 shows the logistic regression analysis of predictors for pca detection among the three groups . in the univariate analysis , age ( p=0.003 ) , psa on first ( p=0.001 ) and second biopsy ( p<0.001 ) , and psad ( p=0.001 )
were significantly different in patients who were diagnosed with pca . in the age - adjusted analysis , of these factors , psa on first ( p=0.005 ) and second biopsy
( p<0.001 ) and psad ( p=0.001 ) were significantly different . in the multivariate analysis , age ( p=0.038 ) , psa on second biopsy ( p<0.001 ) , and psad ( p<0.001 )
in the present study , we investigated the differences in the cancer detection rate , gleason scores on second biopsy , and unfavorable disease rate after rp among patients with benign diagnosis , hgpin , and asap on first prostate biopsy .
a total of 214 patients ( 16.2% ) were diagnosed with pca on a second biopsy .
patients with older age , a higher serum psa level on second biopsy , and a high psad had an increased risk of pca detection in age - adjusted and multivariate analysis .
the cancer detection rate was significantly higher in patients with hgpin2 and asap on first biopsy .
therefore , when we interpret the results of the first biopsy , we should consider the potential risk of pca according to the number of positive cores in patients with hgpin and asap . to the best of our knowledge ,
this is one of the largest studies in korea that has examined the significance of hgpin and asap cores on first biopsy .
several studies have reported that the cancer detection rate on second biopsy ranges from 25% to 79% and from 21% to 60% in patients with hgpin and asap , respectively . in this study , 33 patients ( 22.1% ) and 17 patients ( 32.1% ) were diagnosed with pca in the hgpin and asap groups , respectively .
reported that the cancer detection rate was higher in patients with multiple cores of hgpin ( 35.9% ) than in those with single - core hgpin ( 22.0% ) . in our study , the cancer detection rate was significantly higher in patients with hgpin2 than in those with hgpin1 ( 30.5% vs. 16.7% , p=0.047 ) .
analyzed a total of 295 patients with asap and reported that pca was detected in 125 patients ( 42.4% ) on second biopsy . in our study , patients with asap also had a significantly higher cancer detection rate than did those with a benign diagnosis ( 32.1% vs. 14.6% , p<0.001 ) .
reported that , when patients were diagnosed with pca on second biopsy , the proportion of gleason scores were as follows : gleason6 was 83% , gleason 7 was 15% , and gleason8 was 4% .
in our study , gleason6 was 53.8% , gleason 7 was 25.0% , and gleason8 was 7.1% .
there was a relatively higher proportion of patients with a gleason score8 and a lower proportion of patients with a gleason score6 in our study .
some studies have reported that patients diagnosed with pca in korea have higher gleason scores than do western patients , and that tendency may be reflected in our study .
reported that the percentages of patients with gleason6 and gleason8 were 48.1% and 13.6% , respectively .
however , there were no statistically significant differences in gleason scores among three groups ( p=0.324 ) in this study .
of the 214 patients diagnosed with pca on a second biopsy , 131 patients ( 61.2% ) patients overall underwent rp
. unfavorable disease after rp was detected in 8 patients ( 8.3% ) with benign diagnosis , 2 patients ( 8.0% ) with hgpin , and 1 patient ( 10.0% ) with asap .
there were no meaningful differences in the rate of unfavorable disease among the three groups ( benign diagnosis vs. hgpin , p=0.857 , and benign diagnosis vs. asap , p=0.957 , respectively ) .
taken together , the results of hgpin and asap on first biopsy were not correlated with gleason scores on second biopsy or the unfavorable disease rate after rp in this study .
the mean time between the first and second biopsy was 32.8 months in the benign diagnosis group , 30.1 months in the asap group , and 7.5 months in the hgpin group .
if the result of the first biopsy was a benign diagnosis , regular follow - up was performed in 6 months , and each time the patients came to our hospital , their serum psa levels were checked .
if the result of the first biopsy is hgpin or asap , the follow - up interval should be shorter than that for bph .
usually , follow - up was performed in 3 months , and at that time we considered whether a repeat biopsy should be performed . if the psa level was high , we recommended a repeat biopsy more strongly . in this study , there was a significant difference in the intervals between biopsies among the three groups ( p<0.001 ) .
short - term repeat biopsy was done in the hgpin group , whereas the benign diagnosis and asap groups did not differ significantly ( p=0.605 ) .
although the higher rate of cancer detection in patients with asap on repeat biopsy has been reported previously , the timing of the repeat biopsy was delayed more than in those with hgpin .
one possible explanation of this finding is that we may underestimate the risk of asap and perform a delayed biopsy in some of these patients .
recently , on the basis of the results of this study , we have changed the institutional policy for performing a repeat biopsy .
short - term repeat biopsy in 6 months is recommended more strictly in patients with asap .
the differences in the number of biopsy cores could result in an underestimation of positive cores in the hgpin and asap groups .
we can not exclude the possibility of actual hgpin2 patients being misclassified as hgpin1 in the sextant biopsy group .
third , we did not analyze the number of the cohort receiving a 5- reductase inhibitor between the first and second biopsy , which could affect the serum psa level . also , the time between the first and second biopsy differed among the three groups , which also affected the bias with 5- reductase inhibitor .
the effect of a 5- reductase inhibitor may be more significant in some groups and not significant in other groups .
thus , we can not rule out that the use of 5- reductase inhibitors may have influenced the results of the present analysis .
in summary , we compared the cancer detection rate , gleason scores , and the rate of unfavorable disease to investigate differences in patients with benign diagnosis , hgpin , and asap on first biopsy .
the cancer detection rate was much higher in patients with multiple cores of hgpin and at least one core of asap .
old age , a high psa level on second biopsy , and high psad were associated with an increased risk of pca detection .
 purposeto investigate the differences in the cancer detection rate and pathological findings on a second prostate biopsy according to benign diagnosis , high - grade prostatic intraepithelial neoplasia ( hgpin ) , and atypical small acinar proliferation ( asap ) on first biopsy.materials and methodswe retrospectively reviewed the records of 1,323 patients who underwent a second prostate biopsy between march 1995 and november 2012 . 
 we divided the patients into three groups according to the pathologic findings on the first biopsy ( benign diagnosis , hgpin , and asap ) . 
 we compared the cancer detection rate and gleason scores on second biopsy and the unfavorable disease rate after radical prostatectomy among the three groups.resultsa total of 214 patients ( 16.2% ) were diagnosed with prostate cancer on a second biopsy . 
 the rate of cancer detection was 14.6% in the benign diagnosis group , 22.1% in the hgpin group , and 32.1% in the asap group , respectively ( p<0.001 ) . when patients were divided into subgroups according to the number of positive cores , the rate of cancer detection was 16.7% , 30.5% , 31.0% , and 36.4% in patients with a single core of hgpin , more than one core of hgpin , a single core of asap , and more than one core of asap , respectively . 
 there were no significant differences in gleason scores on second biopsy ( p=0.324 ) or in the unfavorable disease rate after radical prostatectomy among the three groups ( benign diagnosis vs. hgpin , p=0.857 , and benign diagnosis vs. asap , p=0.957 , respectively).conclusionspatients with multiple cores of hgpin or any core number of asap on a first biopsy had a significantly higher cancer detection rate on a second biopsy . 
 repeat biopsy should be considered and not be delayed in those patients . 
INTRODUCTION
MATERIALS AND METHODS
1. Patients
2. Comparisons
3. Procedures
4. Statistical analysis
RESULTS
DISCUSSION
CONCLUSIONS