An evaluation of modified transperineal template guided saturation biopsy in the diagnosis of prostate cancer

The unique situation where there is persistent clinical suspicion of prostate cancer (PCa) despite repeated benign histology from conventional prostate biopsy is a diagnostic dilemma for clinicians and patients. Transperineal template guided saturation biopsy (TTSB) has a high cancer yield in this group, but is associated with unacceptably high morbidity particularly high rates of acute urinary retention (AUR). As localised PCa rarely involves periurethral area at the base, we hypothesised that urethral trauma from extensive sampling of this area is a major trigger factor for AUR. This thesis presents data from modified periurethral sparing TTSB technique to determine whether the risk of AUR is reduced compared with rates reported in the literature, without compromising cancer yield and investigates biochemical predictors of pathological outcome and role of pre-biopsy MRI in this group. Three hundred and three men with persistent clinical suspicion of PCa despite a median of 2 (range 1-6) sets of negative biopsies were investigated. Patients prospectively completed a questionnaire evaluating bleeding, pain (visual analogue scale, range 0-10) and analgesic requirements which were assessed at 1 hour post biopsy and on days 1, 3 and 7. Serum PSA, PSAD and %fPSA were documented and evaluated for their ability to predict PCa diagnosis, Gleason score and cancer volume. Furthermore, a pre-biopsy magnetic resonance imaging (MRI) was performed and abnormalities in 4 anatomical quadrants were compared with TTSB to assess whether pre-biopsy MRI could defer need for TTSB or allow a more targeted biopsy regime. Median age was 64 years (range 43-85). PCa was diagnosed in 167 of 303 men (55.1%) from median of 29 cores [range 16-43, Gleason 6 (29.9%), 7 (45.5%) and 8-10 (24.6%)] and 140 (83.8%) were clinically significant with 77.2% of cancers involving the anterior region. AUR occurred in 23 men (7.6%). On multivariate analysis, only prostate volume predicted AUR (P=0.004). Pain was minimal (peak on day 1, mean 0.8 out of 10), requiring simple analgesia in 27% on day 1, mostly for mild perineal discomfort. Haematuria (75%) and rectal bleeding (20%) significantly decreased over one week, with 33% still experiencing haematospermia at this stage. PSAD (AUC 0.76) was more predictive of cancer diagnosis compared to 0.71 for %fPSA and pre-TTSB PSA respectively. The overall sensitivity and specificity of MRI for cancer diagnosis were 65% and 77% respectively with multiparametric MRI showing more accuracy with sensitivity and specificity of 83% and 95% respectively compared to other MRI sequences. Of the 24 false negative MRI cases, 16 (67%) were clinically significant. So complete prostate mapping should continue at present. In conclusion, this thesis demonstrates that clinical suspicion of PCa despite negative histology from conventional TRUS Biopsy should not be disregarded, as a significant proportion harbour aggressive disease. Modified TTSB is well tolerated with low risk of AUR. Presentations of aspects of this thesis at key regional, national and international urology meetings have generated interest and helped set up dedicated units in the region for PCa diagnosis in this group. Questions raised in this study provide backbone for future research in this field.