








































This is an open access article under the terms of a license that permits non-commercial use, provided the original work is properly cited.  
© 2023 The Authors. Société Internationale d'Urologie Journal, published by the Société Internationale d'Urologie, Canada.

Key Words Competing Interests Article Information

Prostate biopsy, targeted prostate biopsy, 
fusion prostate biopsy, cognitive prostate 
biopsy, prostate cancer

None declared. Received on September 8, 2022 
Accepted on January 3, 2023 
This article has been peer reviewed.

Soc Int Urol J. 2023;4(2):142–144

DOI: 10.48083/RYRF4858

Fusion Biopsy, not Cognitive, Is the New Gold Standard

Alessandro Marquis, Giancarlo Marra, Paolo Gontero

Azienda Ospedaliera Universitaria Città della Salute e della Scienza, University of Turin, Department of Surgical Sciences, Division of Urology, Turin, Italy

Abstract

To date, although some benefits resulting from a software-guided technique are undeniable, no clear superiority 
of fusion over cognitive targeted biopsy (COG-TB) has been supported by strong evidence. We discuss potential 
causes of trials failing to show the superiority of fusion TB (FUS-TB) and highlight its advantages over the cognitive 
approach.

One possible reason why current literature showed contradictory evidence in supporting FUS-TB may be the lack 
of high-quality well-designed trials. Indeed, most of the studies addressing this issue have considerable limitations, 
such as underpowering, small sample size, lack of randomization, and poor generalizability. A second reason may be 
the inclusion in the majority of trials of a wide spectrum of MRI-lesions, a scenario in which the benefits of FUS-TB 
may be less evident. In fact, some of the few studies considering smaller targets demonstrated higher accuracy for the 
FUS technique. As concerns the advantages of FUS-TB, the opportunity offered by some fusion systems of storing 
information useful for planning and/or follow-up active surveillance, focal therapy, and radical prostatectomy, as well 
as a reported faster learning curve, are strong points supporting the fusion approach.

In conclusion, the potential advantages when targeting smaller lesions together with the storage capability to guide 
patient management after the biopsy and an easier learning curve may make the FUS approach the more appropriate 
technique for performing TB.

Commentary

When MRI is positive, current guidelines strongly recommend a prostate biopsy combining systematic (SB) and 
targeted (TB) cores[1]. The MRI target can be sampled through a cognitive guidance, a US/MRI fusion software or, 
less frequently, a direct in-bore guidance[2]. To date, there is no strong evidence to support the superiority of either 
one of these methodologies. However, when comparing the fusion and the cognitive approaches, it is undeniable that 
fusion has some advantages. We discuss potential reasons that trials fail to show clinically significant differences and 
highlight some advantages of a software over a cognitive-based TB.

Evidence from trials is contradictory
Some RCTs may have failed in capturing clinical benefits of the fusion over the COG-TB while others did not 
highlight significant advantages. Overall, all these studies suffer from considerable limitations. Notably, the FUTURE 
trial, which included 665 men with prior negative SB to undergo fusion versus cognitive versus in-bore TB, reported 
a higher clinically significant prostate cancer (PCa) detection rate for the fusion than the cognitive group, although 
not reaching statistical significance (34.2% versus 33.3%, P > 0.9)[3]. However, the primary endpoint resulted clearly 
underpowered with only 79 and 78 patients randomized for FUS and COG respectively versus 152 per group originally 
planned in the sample size calculation. Furthermore, only men with prior negative SB were included thus making the 
results not generalizable to all patients with PCa suspicion based on MRI findings.

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The PAIREDCAP study is a paired cohort trial which 
included 248 biopsy naïve patients undergoing 12 SB 
followed, in sequence, by 3-cores COG-TB and 3-cores 
FUS-TB[4]. The csPCa detection rate of FUS-TB was 
7% higher than that of COG-TB (54.0% versus 46.8%) 
and similar difference was shown also at the per-core 
analysis (38.1% versus 33.3%). Although the trial was 
not powered to detect differences in the detection rate 
between the 2 techniques, these findings may support a 
potential advantage of FUS-TB even in the biopsy naïve 
population.

A more recent RCT investigated the diagnostic yield 
of fusion versus COG-TB in 199 men, all biopsy naïve 
and randomized head-to-head[5]. The study was 
powered with 200 patients under the authors’ assump-
tion of a 15% higher detection rate for FUS-TB.  
The results confirmed the hypothesised advantage of 
FUS: both the overall and csPCa detection rates were 
significantly higher in the fusion than in the cognitive 
group (44.4% versus 31.0%, P = 0.035 and 33.3% versus 
19.0%, P = 0.016, respectively). The average positive cores 
number was also higher in the fusion arm (13% versus 
8%, P = 0.045). Notably, the authors acknowledged in the 
discussion that in order to prove a 5% advantage of 
fusion over COG-TB (as current literature data seem to 
show), a total of 1776 patients would be needed, a 
number that exceeds the accrual of any available trial so 
far conducted and confirming that solid evidence in this 
respect is still lacking.

Size of MRI lesion
This may be another reason why some studies failed 
in showing clinically significant differences in favour 
of FUS-TB. It is reasonable that larger targets are 
likely to be more easily sampled using COG-TB, while 
with smaller lesions, FUS-TB may have significant 
advantages. Existing evidence has shown a high grade 
of targeting precision for the FUS system, with accuracy 
of 99% for lesions ≥ 6 mm and of 96% for 5 mm lesions. 
Smaller targets are less likely to be adequately sampled 
using only 1 targeted bioptic core (61% for 3 mm lesion), 
but the probability increases to 94% with 3 cores[6]. 
Therefore, fusion software is likely able to ensure levels of 
precision seldom achieved for small lesions in a cognitive 
setting.

Mean target size usually detected at MRI is 12 mm 
(IQR 8 to 15 mm)[7]; therefore, it is not surprising that 
in the majority of the main trials comparing fusion and 
COG-TB, mean lesion size ranged from 11 to 14 mm 
[3–5,8], more than double the minimum detection 
threshold of MRI. In this “wide-lesion” scenario, 
FUS-TB benefits may be less evident. The PROFUS trial 
analysed the fusion versus COG-TB diagnostic accu-

racy in a cohort with a slightly lower average size lesion  
(9 mm [IQR 7 to 13 mm]) and found a borderline signif-
icance in favour of FUS-TB in terms of per-target csPCa 
detection rate (20.3% versus 15.1%, P = 0.052). Smaller 
target diameter was identified as one of the most influ-
ential factors for cancer detection in the fusion group, 
further supporting the view that FUS-TB provides the 
greatest impact when targeting smaller lesions that may 
be difficult to sample using COG-TB[8]. Importantly, 
previous retrospective series observed a significant 
advantage for FUS-TB with a magnitude of effect that 
was larger in lesions below 1 cm (FUS-TB 64.0% versus 
40% COG-TB, where targets ≤ 10 mm were 52% versus 
21%, respectively)[9].

FUS-TB is more informative
Some fusion systems allow exact recording of the 
location of positive cores, which is key in the era of 
precision PCa diagnostics and treatment when planning 
future management. This has implications for (1) a more 
accurate follow-up biopsy during active surveillance; 
(2) a more precise delivery and then follow-up of focal 
therapy; (3) radical prostatectomy planning[8].

Fusion may be easier to learn
A higher operator expertise may be required to achieve 
comparable outcomes with a cognitive approach. Stabile 
et al. retrospectively evaluated both the detection rate 
and its improvement in 244 men during the learning 
curve[10]. There was no clear increase in detection 
of csPCa overall (58% versus 45% P  =  0.07) but the 
detection of csPCa on a per-target analysis was higher 
with FUS-TB (57% versus 36%, P = 0.002). Interestingly, 
not only the fusion technolog y but also operator 
expertise was an independent predictor of cancer 
detection. In addition, the COG-TB learning curve was 
steeper, and the number of procedures needed to reach 
the plateau lower for FUS-TB.

Conclusion
While current evidence does not strongly support the 
superiority of fusion over cognitive TB, it seems plausible 
that FUS-TB is more accurate in targeting smaller 
lesions. Major trials have generally been underpowered 
and have yielded contradictory evidence; however, most 
have included large lesions, while the advantages of 
FUS-TB are likely more evident for smaller targets. The 
learning curve may also be shorter for fusion compared 
with COG-TB. In the era of precision medicine, 
advantages that are not clinically measurable, including 
storage capability to guide patient management after the 
biopsy, should also be considered.

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