prostate cancer is the most frequently diagnosed solid organ cancer in men and is the second most common cause of cancer death .
psa screening and testing has been shown to reduce mortality from prostate cancer and increase life expectancy . however , this has caused a tendency towards over - detection of low risk prostate cancer and , as a result , treatment of both indolent and aggressive prostate cancer .
radical treatment is associated with significant morbidity , predominantly with incontinence and erectile dysfunction ; as such , it is vital that patients are accurately staged and appropriately counselled before making their treatment decision . currently , investigations for those with elevated psa revolve around transrectal ultrasound guided prostate biopsies .
this involves taking 12 biopsy cores in a systematic approach as supported by aua and eau guidelines [ 4 , 5 ] .
this is due to the risk of seeding intestinal flora into the prostate and the limited antibiotic penetration of prostatic tissue .
the risk of major infection has been reported as high as 5.5% in some studies .
another limitation is the relatively high proportion of false negative results that occur with transrectal biopsies , having been shown to miss up to 30% of prostate cancers .
even if prostate cancer is detected on transrectal biopsy , a significant proportion is upgraded after template biopsy or after histological analysis of the radical prostatectomy specimen [ 8 , 9 ] .
this is due to the complex , heterogeneous and multifocal nature of prostate cancer , as well as the challenging aspect of sampling the anterior part of the prostate transrectally . as a result
, there may be a proportion of patients who have been falsely reassured by being diagnosed with low - grade disease and thus chose their treatment based on incomplete information .
transperineal template - guided prostate biopsies ( template biopsies ) have been shown to overcome some of these limitations .
this is due to the greater number of biopsy cores taken , and due to the fact that the anterior portion of the gland is accessed and biopsied with greater certainty . as a result
subsequently , the rate of detection of template biopsies in those who have previously had a negative transrectal biopsy has been reported to be as much as 39% .
this study aims to evaluate the use of transperineal template - guided prostate biopsy presently in use at our unit .
we also aim to investigate the detection rate of prostate cancer in those with previously negative transrectal biopsies and the upgrade rate of those on active surveillance for gleason 3 + 3 = 6 prostate adenocarcinoma following transperineal template - guided prostate biopsy .
all data from patients having undergone a transperineal template - guided prostate biopsy were prospectively collected over a 22-month period .
these scans were performed and reported in a manner consistent with the standards and recommendations approved by a european consensus meeting   using the  prostate imaging reporting and data system ( pirads ) score ( table 1 ) .
patients who had previously received brachytherapy or had undergone template biopsies for anorectal abnormalities were excluded .
pi - rads score as adapted from the esur mr guidelines 2012 transperineal template - guided prostate biopsies were performed as ambulatory day - case surgery under general anaesthesia by a consultant urologist .
patients were given prophylactic antibiotics ( gentamicin 240 mg intravenously and metronidazole 500 mg rectally ) at induction of anaesthesia and placed in the dorsal lithotomy position .
multiple transperineal prostatic biopsy cores were taken in a systematic fashion using a 5 mm brachytherapy template grid as previously described .
the total number of cores varied with the size of the prostate ; however , a minimum of 24 named sectors were biopsied .
four regions were sampled anteriorly and four regions were sampled posteriorly from each of 3 transverse planes ( figure 1 ) . if the prostate was found to have a large volume and further sampling was needed , then further regions were sampled from a fourth transverse plane at the surgeon 's discretion .
schematic of the prostate identifying the three transverse planes and the four sagittal planes that make up the 24 named sectors that are biopsied .
transperineal template - guided prostate biopsies were performed as ambulatory day - case surgery under general anaesthesia by a consultant urologist .
patients were given prophylactic antibiotics ( gentamicin 240 mg intravenously and metronidazole 500 mg rectally ) at induction of anaesthesia and placed in the dorsal lithotomy position .
multiple transperineal prostatic biopsy cores were taken in a systematic fashion using a 5 mm brachytherapy template grid as previously described . the total number of cores varied with the size of the prostate ; however , a minimum of 24 named sectors were biopsied .
four regions were sampled anteriorly and four regions were sampled posteriorly from each of 3 transverse planes ( figure 1 ) . if the prostate was found to have a large volume and further sampling was needed , then further regions were sampled from a fourth transverse plane at the surgeon 's discretion .
schematic of the prostate identifying the three transverse planes and the four sagittal planes that make up the 24 named sectors that are biopsied .
a comparison between patients with positive template biopsy results and negative template biopsy results is presented on table 2 ( excluding those on active surveillance and those post - radiotherapy ) .
there is no significant difference between demographic data ; however , the mri results indicate that a positive template biopsy is associated with a significantly greater pirads score than negative template biopsies ( p < 0.05 ) .
comparison of subjects with positive transperineal template biopsies with those with negative transperineal template biopsies ( excluding the cases on active surveillance and those post - radiotherapy ) overall , 47% of cases were found to have prostate cancer on template biopsy , of which gleason 3 + 3 = 6 was most commonly identified ( figure 3 ) . in those with previous negative transrectal biopsies , the majority had either one or two previous transrectal biopsies ( figure 4 ) .
overall , 39.5% of cases with previous negative transrectal biopsies were subsequently found to have prostate cancer on template biopsy .
this shows that transrectal biopsy had a 39.5% false negative rate when compared to template biopsies this figure was maintained regardless of whether patients had undergone one , two or three negative transrectal biopsies ( figure 5 ) .
prostate cancer detection rate using transperineal template - guided prostate biopsies in those with previous negative transrectal prostate biopsies .
47.5% of cases on active surveillance for gleason 3 + 3 = 6 prostate cancer were upgraded following template biopsy ( figure 6 ) .
prostate cancer upgrade rate following transperineal template - guided prostate biopsies in those with gleason 3 + 3 = 6 prostate adenocarcinoma on active surveillance .
haematuria and sepsis requiring admission were uncommon and occurred in 1% and 0.5% of cases respectively .
there was no significant difference in case mix between those who took tamsulosin and those who did not .
the risk of aur in those using a single prophylactic dose of tamsulosin was lower at 5.3% .
therefore , the numbers needed to treat ( nnt ) to prevent one episode of retention was found to be 13 .
the majority of patients undergoing the template biopsies had previous negative transrectal biopsies but persistently elevated psa and/or abnormal mri prostate findings ( figure 2 ) .
hodge et al . described the original sextant transrectal biopsies , which have been found to have a false negative result of up to 33% .
our study supports this with transrectal biopsies having a 39.5% false negative rate compared to template biopsy
. the greater detection rate of template biopsies is probably due to three main reasons .
it makes logical sense that increasing the number of cores taken at the time of biopsy would increase the detection rate .
template biopsies take a minimum of 24 cores , whereas standard transrectal biopsies require 12 cores .
another reason is the ease and greater certainty of sampling the anterior prostate using template biopsies .
approximately 1 in 5 patients with prostate cancer have anterior prostate involvement , and in those patients with previous negative transrectal biopsies the anterior region is found to have the greatest density of prostate cancer . as a result ,
our study shows that out of the cases that were found to have prostate cancer on template biopsy after negative transrectal biopsies , 83% of patients overall had anterior prostate cancers . of those 44%
the final reason why template biopsies have a greater detection rate compared to transrectal biopsies , is due to the targeting that can be achieved using pre - template biopsy mri scans .
this means that any named sector within the prostate , with an abnormality observed on mri , can be targeted and more cores can be taken from that location to help achieve a more accurate diagnosis .
it was also shown that the detection rate from template biopsies was maintained at a level of approximately 39.5% , regardless of whether patients had undergone one , two or three previous negative transrectal biopsies ( figure 5 ) .
we therefore recommend considering a template biopsy after one negative transrectal biopsy in patients with clinical suspicion .
a proportion of patients had template biopsies as part of the monitoring for active surveillance for gleason 3 + 3 = 6 prostate cancer .
we found that 47.5% of these cases were upgraded following template biopsies ( figure 6 ) .
this is supported by another study by caster et al , which showed that the upgrade rate of those with biopsy proven gleason 6 prostate cancer , with a psa < 10 , was as much as 43% when compared to the radical prostatectomy specimen . as a result
we suggest that template biopsies should be considered before recommending active surveillance , or should be included as part of the active surveillance regime , rather than standard transrectal biopsies .
it must be remembered , however , that this upgrade rate could be explained by the fact that the cohort of patients we have sampled are selected . according to current guidelines the active surveillance protocol requires psa tests every 36 months , digital rectal examination every 612 months and a repeat transrectal biopsy a year after diagnosis , then every few years .
this means that the referring clinician considered these cases to be suspicious . in addition , mri scans had been performed on this cohort of patients .
this means that the referring clinician also must have come to the conclusion , based on the mri result , that repeat transrectal biopsies were unlikely to detect the abnormality in question , so template biopsies were ordered .
this is likely to skew the results and may explain the high upgrade rate ; however , the results are consistent with previously published data , which showed that the upgrade for active surveillance could be as much as 3867.6% [ 21 , 22 ] .
this is significantly greater than the risk of aur with transrectal biopsies , which in a systematic review was reported as 1.7% .
one reason for this increase is due to the greater number of cores taken at template biopsy . a study by pepe et al .
looked into complication rates of 3000 patients who underwent 12 vs. 18 vs. 24 core template biopsies .
it showed that the risk of aur increased by 4.1% , 7.1% and 11.1% respectively . as a result
, the number of cores taken has a direct correlation with the rate of aur .
although there is no actual evidence , we believe this is probably due to the increased swelling and oedema that is caused by the increased core numbers . furthermore , with swelling of the anterior part of the prostate being present with template biopsies , there is greater likelihood of concentric compression of the prostatic urethra .
this swelling then causes temporary retention that usually resolved once the prostate has had time to recover . as a result
the overall aur rate of 12.5% seems to be consistent with the previously published data of 11.1% .
buskirk et al .   showed that there was a correlation between gland size and the likelihood of going into aur following template biopsies .
subjects with a gland size of < 50 ml exhibited an aur rate of 4% , whereas those with a gland size of > 50 ml had an aur rate of 20% ( p = 0.039 ) .
we found that the use of a single dose of tamsulosin 400 mcg at the time of template biopsy significantly reduced the rate of aur , with an nnt score of 13 to prevent one episode of retention .
the use of tamsulosin has already been shown to help improve international prostate symptom scores ( ipss ) and maximum flow rates in transrectal biopsies in a randomized prospective study .
our data shows that a single dose can also be used to help reduce the rate of aur in template biopsies and so improve morbidity .
another indication for the use of template biopsies is to provide evidence of unifocal disease .
if this is the case , then the patient can be considered for focal therapy .
due to the complex , heterogeneous and multifocal nature of prostate cancer , focal therapy relies on accurate patient selection . as a result ,
however , according to the national institute of clinical excellence ( nice ) guidelines   and the european association of urologists ( eau ) guidelines , cryotherapy can only be offered in those who are unsuitable for surgery or radiotherapy , furthermore high - intensity - focused ultrasound ( hifu ) should only be offered as part of a trial .
consequently , our unit did not look into this indication for template biopsies and further studies would need to be performed to evaluate this further .
our unique series complements previously published data on transperineal template - guided prostate biopsies , showing it to be safe and accurate .
our study suggests that due to the relatively high detection rate one must consider template biopsies after one negative transrectal biopsy if there is clinical suspicion .
in addition , those with gleason 3 + 3 = 6 prostate cancer who are considering active surveillance should be offered template biopsies so more accurate staging can be done and appropriate counselling performed .
however , to counter the increased risk of aur we have found a single dose of tamsulosin to be beneficial .
all procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee , and with the 1964 helsinki declaration and its later amendments or comparable ethical standards .
 introductionwe aim to present transperineal template - guided prostate biopsy ( template biopsy ) outcomes at a tertiary referral centre . 
 furthermore , to identify the detection rate of prostate cancer in those with a previous negative transrectal ultrasound guided prostate biopsy and the upgrade rate of those on active surveillance for gleason 3 + 3 = 6 prostate adenocarcinoma.material and methodswe conducted a prospective study of 200 consecutive men who underwent template biopsy over a 22-month period in a tertiary referral centre , using a standard 24 region template prostate biopsy technique . 
 indications and histology results , as well as complications , were recorded.resultsmedian age was 67 years and median psa was 10 ng / ml . 
 overall detection rate was 47% . 
 39.5% of cases with previous negative transrectal biopsies were found to have prostate adenocarcinoma . 
 47.5% of cases on active surveillance for gleason 3 + 3 = 6 prostate adenocarcinoma were upgraded . 
 the most frequent complication was acute urinary retention at a rate of 12.5% , however , the use of a single prophylactic dose of tamsulosin was found to be beneficial , with 13 cases needed to treat to prevent one episode.conclusionstemplate biopsies are safe and efficacious with an overall detection rate of 47% in the present series . 
 due to the high detection rate , one must consider template biopsy following one negative transrectal biopsy where there is persistent clinical suspicion . 
 furthermore , those considering active surveillance for gleason 3 + 3 = 6 disease should be offered template biopsy to confirm the grade of their disease . 
INTRODUCTION
MATERIAL AND METHODS
Transperineal template biopsy technique
RESULTS
DISCUSSION
CONCLUSIONS
CONFLICTS OF INTEREST
ETHICAL APPROVAL