Background

Prostate cancer (PCa) is the most common solid organ cancer and the commonest cause of cancer-related death in men in the UK. There are approximately 48,500 new cases diagnosed in the UK each year, and around 11,700 men die from this malignancy each year, whilst the lifetime risk of being diagnosed with PCa is around 1 in 8. PCa incidence is increasing due to wider use of PSA testing of asymptomatic men coupled with an ageing population. During investigation for suspected PCa, men currently receive a PSA test followed by an MRI scan and a prostate biopsy.

Currently, most PCa cases are diagnosed by TRUS biopsy performed in the outpatient clinic setting. However, whilst TRUS biopsy has been performed for decades to sample the prostate gland, it can be difficult to biopsy the anterior and apical regions of the prostate using the TRUS biopsy technique, making targeting and comprehensive sampling difficult in some cases. It is therefore recognised that TRUS biopsy can miss ~30% of clinically significant PCa cases, meaning ~15,000 men per year in the UK may be falsely reassured by an initial negative TRUS biopsy result, or may need to undergo further biopsies as a follow-up procedure.  Moreover, TRUS biopsy has a reported 3-5% associated risk of urinary infection due to the transrectal nature of the biopsy, additionally there is ~1-2% risk of urosepsis and hospitalisation based on national data, despite antibiotic prophylaxis, and a small but important risk of intensive care admission, and in rare serious cases, death.

TP biopsy, in general, has an advantage over TRUS in that the anterior region of the prostate gland can be more readily biopsied due to the ‘in-line’ or ‘parallel’ approach that the biopsy needle takes to the long axis of the prostate gland. The available evidence suggests that LATP has a high rate of PCa detection, both in targeting MRI-detected lesions and through systematic biopsies of the entire prostate gland. Overall, the reported detection rate of clinically significant PCa, defined as Gleason grade group ≥2 (i.e. any Gleason pattern 4) disease, is 50-65% (5-7). The ability of LATP to increase the detection rate of anterior zone PCa compared with TRUS is an important consideration of these two biopsy techniques. In one study, 52.7% of PCa cases had some element of anterior gland involvement, and 9.7% of cases had tumours exclusive to the anterior zone. However, given differences in biopsy techniques in reported observational cohort series and the lack of RCTs, there is no level one evidence that LATP leads to a higher detection rate of clinically significant PCa versus TRUS biopsy.

Serious infection is another main concern of TRUS biopsy, mandating the prophylactic use of broad spectrum antibiotics such as fluoroquinolones which themselves can be toxic and are controlled in their use. Unfortunately the incidence of urosepsis continues to rise worldwide due to antibiotic resistance and it remains critical to follow guidance on antibiotic stewardship wherever possible. In contrast to TRUS biopsy, TP biopsy allows the needle to avoid contamination from rectal flora by taking a transcutaneous route to the prostate. The infection rate from LATP biopsy in observational series is low at <1%. A recent report of LATP as primary biopsy technique in 1,287 consecutive individuals demonstrated only 4 patients (0.3%) had lower urinary tract symptoms suggestive of infection post-procedure, only 1 had a positive urine culture, and only 1 required hospital admission for persistent hypotension post-biopsy. In Oxford we reported our initial experience using LATP in other settings (repeat biopsy, and in active surveillance). We have observed a low post-LATP infection rate of 0.6%. A recent audit of our last 6 months of TRUS demonstrated a post-procedure urinary infection rate of 3.7%, and risk of hospitalisation for urosepsis of 1.7%, despite antibiotic prophylaxis in accordance with contemporary published series. Taken together the available evidence suggests that the infection rate from LATP is likely to be lower than for TRUS, however to date this has not been demonstrated in an RCT. The absence of level one evidence comparing LATP with TRUS biopsy means that the introduction of the LATP biopsy technique is being undertaken on an ad hoc basis at various UK centres, resulting in geographical variation in availability of this technique across the UK.

It is possible that there are other differences between TRUS and LATP biopsy in terms of complications post-procedure.The rate of acute urinary retention requiring catheterisation was reported to be 1.6% in a recent observational series of LATP biopsy. Moreover, the rate of transient erectile dysfunction after LATP biopsy may be different following LATP compared to TRUS biopsy. However, like TRUS, LATP is generally well tolerated by most patients, with only mild levels of discomfort during the procedure, demonstrating that it is feasible in the outpatient clinic setting. 

The lack of RCT-based evidence means that the National Institute for Health and Care Excellence (NICE) in the UK, and similar bodies globally, are unable to make robust recommendations regarding the optimal form of prostate biopsy technique, highlighting the urgent need for the primary research described in this proposal. It is imperative to investigate whether LATP biopsy, with potentially better prostate sampling and fewer potential infection-related side effects but perhaps higher economic costs (although this may in part be mitigated by a reduction in the need for repeat biopsies), is superior to TRUS biopsy which may have higher infection-related complications but fewer other side effects.