title: Multiparametric MRI and MRI/US fusion guided biopsy in the diagnosis of prostate cancer
Creators: name: Szewczyk-Bieda, Magdalena
Publisher: name: University of Dundee
publisherIdentifier: https://ror.org/03h2bxq36
publisherIdentifierScheme: ROR
Year: 2022

description: Background: Established diagnostic pathway for detection of PCa, based on non-targeted gland sampling, has many limitations. There is strong evidence that Multiparametric MRI (MP MRI) performed prior to prostatic biopsy reduces unnecessary biopsies and over diagnosis of clinically insignificant disease as well as improves detection of clinically significant (CS) prostate cancer (PCa). At the time of writing of this thesis, pre-biopsy MP MRI has already been incorporated into the recommended diagnostic pathway for urgent suspected PCa as per NICE 2019 guidance. Although there is growing body of research on the subject, there are still areas, which lack high level data from randomised trials and studies, using radical prostatectomy (RP) specimen as a gold standard.

This thesis aimed to investigate the ability of MP MRI to detect foci of CS PCa at per-lesion level, in comparison with RP specimen and to assess the added value of MR guided targeted biopsies, in addition to standard trans rectal (TRUS) biopsies, in confirming the presence of CS disease in a setting of a randomised controlled trial.

Methods: The data were collected during prospective, multicentre parallel-group study with subgroup randomization, which has been granted all the necessary approvals including registration at CLINTrials.gov, NCT02745496.

It comprised of two main parts:

A prospective study on 89 patients suspected of having PCa, with subsequent positive pre-biopsy MP MRI, who underwent RP as a curative treatment option. In this group, diagnostic accuracy of MP MRI in detection of PCa and CS PCa with gold standard of histology of RP specimen on per-lesion and per-patient levels were performed, using customised molds for precise correlation;

Added value of MR guided targeted biopsy was assessed in a setting of a prospective randomized controlled trial of 603 patients, suspected of having PCa and with positive MP MRI (assessed using PIRADS v2 system), who underwent either MRI-trans rectal US fusion targeted biopsy (FUS-TB) used in conjunction with TRUS biopsies or standard of care TRUS biopsies alone.

Results: A total of 624 biopsy-naïve participants with clinical suspicion of organ-confined PCa were enrolled into the study over a period of 66 months (February 2015-August 2020). 603 participants underwent pre-biopsy MP MRI and those with positive MP MRI result (413/603) were subsequently randomised to undergo either TRUS/FUS-TB biopsies (intervention) or TRUS biopsies (standard of care).

89 participants with positive MP MRI, who opted for RP as a curative treatment option, had their MP MRI compared to RP specimen using customised molds, enabling lesion-level analysis. This revealed high sensitivity of pre-biopsy MP MRI in detection of foci of CS PCa of 72%, with relatively high specificity of 71% and reassuringly balanced PPV and NPV of 78% and 64.1% respectively, when comparing to RP specimen as a gold standard.
91% of all PIRADS 5 lesions, 77% of all PIRADS 4 and 48% of all PIRADS 3 lesions corresponded to CS PCa foci on RP.
Majority of PCa foci missed on MP MRI were non-significant (NS) PCa, the CS PCa missed were in large proportion situated in the anterior half of the gland and smaller than 15 mm in size.

TRUS/FUS-TB pathway detected CS PCa in 130/207 (62.8%) patients, 28/130 (21.5%) by FUS-TB only, 17/130 (13%) by TRUS only and 85/180 (65.3%)by both techniques combined and NS PCa in 21/207 patients (10.1%). The MP MRI positive TRUS alone arm had detected 106/206 CS PCa (51.4%) with 18/206 (8.7%) of NS PCa. The probability of CS cancer detection by TRUS/FUS-TB pathway was statistically significantly higher (p=0.002) than by control TRUS only arm.

The safety profile and reported side effects of the combined biopsy approach was clinically no different than standard TRUS pathway.

Negative MP MRI performed prior to biopsy in biopsy-naïve men, with clinical suspicion of PCa, would have allowed 28% men to avoid biopsy with a risk of missing CS PCa in 5.7% of those patients.

Conclusions: Pre-biopsy MP MRI detected CS PCa with high sensitivity and specificity and avoided over detection of NS PCa (only 4% of NS PCa seen on pathology were detected on MP MRI). The CS PCa missed on MP MRI were in large proportion small and /or situated in the anterior half of the gland.

Combined TRUS/FUS-TB pathway in MP MRI positive patients had significantly higher detection rate of CS PCa than TRUS biopsy alone pathway with a small increase in NS PCa detection as an expense. FUS-TB biopsy alone was non-inferior to TRUS biopsy in diagnosing CS cancer with an added benefit of less cores.

Not performing TRUS in MP MRI negative group would have saved 28% biopsies with a cost of missing CS PCa in 5.7% patients.