By: Dan Sperling, MD
A prospective randomized clinical study (Arsov et al., 2015) [i] ran a well-designed comparison between MRI guided in-bore targeted biopsy vs. combination biopsy (MRI/ultrasound fusion guided biopsy plus conventional transrectal ultrasound (TRUS) guided biopsy). The patients enrolled in the study had a history of at least one previous negative biopsy but had continued suspicion of prostate cancer based on clinical factors such as abnormal PSA and/or digital rectal exam. For this population, diagnosis by conventional systematic TRUS biopsy is especially problematic. Having failed to detect prostate cancer (PCa) once, repeat TRUS biopsy has a disappointingly unsuccessful performance leading to further biopsies.
To compensate for the tendency of conventional TRUS-guided systematic to miss tumors a second or even third time, some clinicians now turn to fusion-guided targeted biopsy in addition to multi-core TRUS biopsies. For those not familiar with fusion guidance, the technology involves uploading previously captured MRI prostate images into software that “marries” or co-registers those static scans with real-time ultrasound imaging. Fusion thus takes advantage of the accurate details captured by multiparametric MRI (mpMRI) and incorporates them into live ultrasound. For urologists who lack access to MRI equipment, and are usually not trained to interpret MRI scans, the fusion-generated images highlight the suspicious areas identified on MRI. Depending on the fusion device, the trajectory of biopsy needles will either be calculated by the software, or the practitioner can cognitively plan the needle trajectory and confirm targeted placement based on the ultrasound images. Theoretically, a fusion-guided targeted biopsy coupled with a random TRUS biopsy greatly diminishes the chance of missing any cancer that is present. In fact, a recent study (Maxeiner et al., 2014) of 128 patients with previous negative biopsies used this combined biopsy method, which resulted in an overall 39.8% rate of detecting PCa. [ii] The detection rate is increased by redundancy: overlapping a 10-14 needle blind biopsy that casts a “wide net” with an additional targeted sampling.
What distinguishes the Arsov study is the question it raises: Is the combined fusion-guided/TRUS method better than targeted biopsies guided by real-time MRI-guided in-bore biopsies? Put another way, does adding fusion-guided targeted biopsy on top of randomized TRUS biopsy confer a significant advantage over TRUS biopsy alone? The Arsov team recruited 267 patients each of whom had at least one prior negative TRUS biopsy and whose PSA was ?4 ng/ml. Approximately 80% of this population was chosen for the prospective randomized comparison study of in-bore MRI-guided targeted biopsy (IB-GB) vs. combination fusion plus TRUS biopsy (FUS + TRUS). The authors also analyzed the distribution of highest Gleason scores, detection rates of significant PCa (Gleason ?7), how many biopsy cores were needed to detect one significant PCa, the rate of positive biopsy cores, and the percentage of tumor involvement per needle core. Following 3 Tesla mpMRI, patients were randomly assigned to one of two groups: 106 patients were assigned to IB-GB (Group A) and 104 to FUS + TRUS (Group B) for a total of 210 in the study cohort. The authors defined the primary endpoint as a demonstration of an overall cancer detection rate of ?60% using FUS + TRUS compared to 40% in the IB-GB group. However, the study was halted when interim analysis showed very different results. The table below summarizes key findings:
|Group A (IB-GB)||Group B (FUS + TRUS)|
|Number of patients||104||106|
|Detection of PCa||37%||39%|
|Highest percentage tumor involvement per biopsy core||48%||42%|
|Mean number of cores||5.6||17|
According to the authors, “This trial failed to identify an important improvement in detection rate for the combined biopsy approach over MRI-targeted biopsy alone.” With nearly equivalent detection rates between groups, the researchers rejected the theory that the combined biopsy approach represents an “important improvement in detection rates.” It is worth pointing out that the Arsov team’s detection rate of 39% for the combined approach is almost identical with the 39.8% rate for the Maxeiner team. Even more noteworthy is that in-bore targeted biopsy generated nearly identical results using roughly 1/3 of the number of needles (average 5.6 for in-bore targeting, average 17 for combined FUS/TRUS).
In summary, for patients with previous negative TRUS biopsies, mpMRI guided in-bore prostate biopsy offers comparable detection rates with dramatically fewer needles. This suggests that real-time MRI-guided targeted biopsies should be considered for first biopsies as a way to avoid unnecessary repeat biopsies.
[i] Arsov C, Rabenalt R, Blondin D, Quentin M et al. Prospective randomized trial comparing magnetic resonance imaging (mri)-guided in-bore biopsy to MRI-ultrasound fusion and transrectal ultrasound-guided prostate biopsy in patients with prior negative biopsies. Eur Urol. 2015 Oct;68(4):713-20.
[ii] Maxeiner A, Fischer T, Stephan C, Cash H et al. [Real-time MRI/US fusion-guided biopsy improves detection rates of prostate cancer in pre-biopsied patients]. [Article in German] Aktuelle Urol. 2014 May;45(3):197-203.