the increase in the aged population , a westernized lifestyle , the development of diagnostic tools , and national surveillance programs for early prostate cancer detection may all have contributed to the increased detection rate of prostate cancer .
checking the serum prostate - specific antigen ( psa ) level and a digital rectal examination ( dre ) are the gold standards for prostate cancer screening . if repeated psa levels exceed 4 ng / ml or prostate nodule or asymmetry are found by dre , transrectal ultrasonography ( trus)-guided needle biopsy is performed to pathologically confirm the diagnosis .
a higher psa value is more frequently associated either with prostate cancer or with advanced disease , even though the opposite opinions have been reported in some cases ( e.g. , prostate cancer prediction with low psa in the case of elderly patients with abnormal dre and trus findings ) .
more than 50% of men with a psa value higher than 10 ng / ml have extra - prostatic disease .
twenty percent of men with a psa higher than 20 ng / ml and 75% of those with a psa higher than 50 ng / ml are found to have pelvic lymph node involvement .
coagulopathy and immunosuppression can be problematic , and severe conditions are contraindications to prostate biopsy .
after trus - guided needle biopsy , most infectious complications are limited to symptomatic urinary tract infection and low - grade febrile illness ; however , recent studies showed that 1.4% of patients will go on to develop a febrile urinary tract infection , bacteremia , or acute prostatitis and require hospitalization for treatment with intravenous antibiotics .
bleeding is the most common complication seen after prostate biopsy , even with normal coagulation parameters .
other complications include acute urinary retention ( aur ) , which may require temporary catheterization , the chance of which is increased with a prior history of benign prostatic hyperplasia and older age .
therefore , particularly in patients with extremely elevated serum psa levels and old age , prostate biopsy to confirm the diagnosis of prostate cancer should be carefully considered owing to possibly fatal complications . to prove the necessity for prostate biopsy in this group
, we reviewed the outcomes of trus - guided prostate needle biopsy in patients with elevated psa levels .
we grouped the patients according to their psa levels and calculated the positive predictive value ( ppv ) .
we retrospectively reviewed the medical records of 1,150 patients who underwent trus - guided prostate needle biopsy for the evaluation of prostate cancer from january 2000 to december 2010 .
patients with a pre - biopsy psa level less than 4 ng / ml were excluded from the study .
we also excluded patients with acute prostatitis and acute urinary retention . in total , 1,121 patients were reviewed in this study .
all patients took antibiotic prophylaxis ( either po quinolones or third - generation cephalosporins ) for 7 days , starting from the day before the biopsy . if any signs or symptoms suggesting urinary tract infection occurred , the procedure was canceled .
patients taking anticoagulation agents stopped the medication for at least 5 days before the biopsy . for most of the patients , 12-core or double sextant biopsy
( i.e. , right peripheral 3 core , right medial 3 core , left peripheral 3 core , and left medial 3 core ) was performed .
one or more cores were added if suspicious hypoechoic lesions or palpable nodules were present on ultrasound or dre . some patients in poor general condition underwent standard sextant biopsy or 8-core biopsy . according to the pre - biopsy psa level , patients were divided into 6 groups ( group a , 4 to 20 ng / ml ; b , 20 to 40 ng / ml ; c , 40 to 60 ng / ml ; d , 60 to 80 ng / ml ; e , 80 to 100 ng / ml ; and f , above 100 ng / ml ) . the patients ' age , pre - biopsy psa level , the result of biopsy ( i.e. , cancer cell type and the gleason score ) , and clinical or pathologic tnm stage were compared .
the mean age of the patients with reported prostate cancer at biopsy was 65.8 years ( range , 34 to 88 years ) and that of the patients with a negative biopsy result was 70.1 years ( range , 38 to 91 years ) .
the mean psa level of the patients with a positive biopsy result was 16.12 ng / ml ( range , 4.82 to 7,176 ng / ml ) .
the mean psa level of patients with a negative result was 10.39 ng / ml ( range , 4.12 to 85.5 ng / ml ) . the detection rate was gradually increased as the pre - biopsy psa level increased . for example , only 21.8% of group a ( i.e. , psa 4 to 20 ng / ml ) had prostate cancer , whereas all 65 patients of group f ( psa > 100 ng / ml ) had cancer ( positive predictive value=100.0% ) , as presented in fig .
1 . all 356 patients had prostate adenocarcinoma . among them , 107 had high - grade cancer ( gleason score 8 ) .
the percentage of high - grade cancer was 30% in total , which increased to 71% in group f ( fig .
2 ) . magnetic resonance imaging ( mri ) was used to evaluate the local extent of disease and the possibility of lymph node involvement , and radionuclide bone scans were also performed to detect skeletal metastasis .
if prostatectomy was performed , the radiologic findings and pathologic results were used to determine the tnm stage .
staging was possible for 311 of the 356 patients , whereas 45 patients had no record due to follow - up loss .
a total of 156 patients ( 50% ) had organ - confined cancer ( table 1 ) .
of the 56 patients who underwent workup for tnm stage in group f ( psa > 100 ng / ml ) , 38 patients had either extra - prostatic diseases ( ct3 - 4 ) or lymph node metastasis ( n1 ) , and 43 patients had positive bone scan metastasis ( m1 ) . combining the results in group f , all patients had advanced prostate cancer ( i.e. , 4 patients [ 7% ] had stage iii and the remaining 52 patients [ 93% ] had stage iv cancer ) . no patient who underwent workup for tnm staging in group f had organ - confined cancer .
an elevated serum psa level is one of the most important features suggestive of prostate cancer . in most cases ,
the psa cutoff of 4 ng / ml is a threshold for performing prostate biopsy .
however , the test is painful and invasive , and various complications have been reported in the literature , albeit not common .
most of the complications were minor and did not require hospitalization , but serious life - threatening complications , such as sepsis , also occurred [ 10 - 13 ] . in general , the risk of prostate cancer is directly related to the psa level .
our analysis demonstrated that a serum psa level higher than 100 ng / ml was 100.0% accurate in predicting the presence of prostate cancer on tissue biopsy .
reported similar results in a large unscreened population . using a subset of 716 patients with a psa value higher than 4 ng / ml , they found a positive predictive value of 98% for psa over 60 ng / ml .
gerstenbluth et al .   reported that , when increased to over 50 ng / ml , the serum psa level was 98.5% accurate in predicting cancer .
thus , they suggested that some highly selected patients may not need to undergo prostate biopsy before androgen deprivation therapy .
there may be a disparity between these reports and ours , possibly resulting from racial differences . in our results ,
the ppv for psa over 50 ng / ml was merely 81.2% , which was lower than the value in the other western studies .
in other words , the negative predictive value for psa over 50 ng / ml was higher .
also , the number of patients who had psa over 50 ng / ml was comparatively smaller , resulting in a difference in ppv from other western studies . in the study by egawa et al . , prostate cancer was present in 59.5% of patients with a psa of 10 ng / ml or higher .
shim et al .   also reported that the risk of positive biopsy for psa levels more than 100 ng / ml was 100% , which was quite similar to our results .
studies of korean populations have also documented a positive predictive value of 93.8% with a psa higher than 100 ng / ml and of 94.7% with a psa higher than 50 ng / ml , which increased to 100.0% in conjunction with an abnormal dre . in the present study ,
the detection rate was 100.0% in the subgroup of patients with a psa of 100 ng / ml or higher . in group e ( psa , 80 to 100 ng / ml )
, one patient with a negative biopsy result was followed up for 6 months and a second prostate biopsy was performed , which confirmed prostate cancer .
we did not include this patient in group f but rather in group e. this is because this study was conducted to verify the necessity for prostate biopsy in diagnosing prostate cancer ; thus , we considered the result of the initial biopsy , not the repeated .
thus , patients with carcinoma reported at their repeated biopsy and not at their initial biopsy were classified as having a negative prostate cancer result .
gerstenbluth et al .   have suggested that a negative biopsy in patients with a psa value of higher than 20 ng / ml is often a false - negative .
the likelihood of cancer is significantly increased if the psa level is persistently high at a subsequent measurement .
the most important role of prostate biopsy is to confirm the diagnosis pathologically , but it also helps to obtain the histologic subtype and to estimate the extent of disease ( e.g. , the number of positive cores and percentage of positive cores ) .
therefore , if cancer is expected to be present in almost 100% of a specific patient group , then the value of biopsy is reduced merely to histologic grading and estimation of disease extent . in our review ,
all 65 patients in group f ( psa > 100 ng / ml ) had adenocarcinoma .
ninety percent of the patients had a gleason grade of 4 or higher ( i.e. , gleason score of 7 or higher ) , and radiologic studies showed that all the cancers were stage iii or iv ( table 1 ) .
in addition , the characteristics of the patients in group f are presented in table 2 .
the patient 's age , body mass index , gleason score , and percentage of positive cores was investigated , but the results showed all patients to have high stages .
therefore , the information from the prostate biopsy ( e.g. , gleason score and the number of positive cores ) does not affect the treatment strategy .
if advanced disease is suspected by a super - high psa level and the results of imaging studies , definitive surgical treatment will not be an option . in our study ,
thus , if cancer is suspected in 100% of the patient group , and both disease extent and histologic subtype can be expected to be in a narrow range , undergoing a needle biopsy would be of little value for this specific group ( i.e. , patients with extremely high levels of serum psa ) .
inflammation due to infection has been found to produce significant psa elevation , and up to 6 to 8 weeks might be needed for the psa value to return to baseline .
psa elevations can also occur as the result of urethral procedures with instrumentation , or following prostatic manipulation , such as the dre .
therefore , in a patient with an increased psa level and any recent history of either acute infection , urinary retention , or urinary tract manipulation , prostate biopsy is not mandatory , and a period of time is required to obtain an accurate psa level [ 19 - 21 ] .
the limits of our study are the relatively small number of patients and the retrospective design .
to validate this cutoff value , a prospective study is needed to compare patients who underwent prostate biopsy with those who did not .
our results suggest the possibility for a biopsy - free diagnosis of prostate cancer , with the criterion of a psa level > 100 ng / ml and evidence of advanced disease in imaging studies . we still recommend that any patient who is considered a candidate for surgery or radiation , despite a high psa level , should undergo biopsy . nevertheless , because prostate needle biopsy can be associated with several adverse effects , if elderly patients with poor general medical condition present with an extremely elevated serum psa level , a tissue diagnosis of prostate cancer may not be required for starting androgen deprivation therapy .
 purposethe results of all prostate biopsies may be positive and suggestive of adenocarcinoma in patients with prostate - specific antigen ( psa ) values higher than 100 ng / ml . 
 we considered that the prostate cancer in patients with high psa might be advanced disease and therefore that the treatment strategy should not be changed according to pathological reports . 
 thus , we assessed the role of prostate biopsy when diagnosing prostate cancer in patients with extremely high psa levels.materials and methodswe reviewed the records of 1,150 cases undergoing prostate biopsies . 
 patients with urinary tract infection and acute urinary retention were excluded . according to the pre - biopsy psa level , patients were divided into 6 groups ( group a , 4 to 20 ng / ml ; b , 20 to 40 ng / ml ; c , 40 to 60 ng / ml ; d , 60 to 80 ng / ml ; e : 80 to 100 ng / ml ; and f , above 100 ng / ml).resultsthe calculated positive predictive value ( ppv ) for prostate cancer was 22% in group a , 54% in group b , 73% in group c , 75% in group d , 89% in group e , and 100% in group f , respectively . 
 pathological diagnosis was adenocarcinoma in all patients in group f ( n=56 ) . among them , 38 patients ( 67.9% ) had lymph node metastasis or extra - prostatic disease or both and 43 patients ( 76.8% ) had bony metastasis . in group f , 
 all cases were advanced prostate cancer ( stage iii or iv ) . 
 all of them received hormonal therapy following diagnosis.conclusionswe suggest the possibility for biopsy - free diagnosis of prostate cancer in patients with extremely high levels of serum psa and evidence of advanced disease in imaging studies , especially in older patients with comorbid medical problems . 