EAU PCa 2018: Prostate Biopsy: Fusion, Systematic or Both?

Milan, Italy (UroToday.com) A summary on the use and the comparison of systematic standard biopsy with mpMRI targeted prostate biopsy was given by Dr. Everaerts.  The ideal biopsy strategy would detect all significant prostate cancer and minimize the detection (and consequent overtreatment) of insignificant prostate cancer. The European Association of Urology (EAU) guidelines state that mpMRI should be used only before repeat biopsy when clinical suspicion of prostate cancer persists despite negative biopsies. When the mpMRI discovers a lesion, this should undergo a targeted biopsy with systematic biopsies as well.

Dr. Everaerts moved on to discuss the problems with systematic TRUS biopsies. First, many men undergo unnecessary biopsies. Second, over detection of clinically insignificant prostate cancer is a real problem. Third, clinically significant prostate cancer can be missed. Lastly, there is great uncertainty about the size, shape, and exact location of the tumor. The question arises whether multiparametric MRI (mpMRI) targeted biopsies are superior to TRUS biopsies in biopsy-naïve patients. The mpMRI targeted biopsies can be performed in three several ways: 1) visual registration, which is called cognitive fusion. 2) Software registration, which is the fusion technique of MRI and US images. 3) Direct in-bore biopsies.

The PRECISION trial1 was a multicenter, randomized trial comparing standard TRUS biopsy to mpMRI targeted biopsy. The mean age of the patients was 64, with a median PSA of 6.7, with 15% having an abnormal digital rectal examination (DRE), and 19% having a positive family history. In the standard TRUS biopsy group, patients underwent the biopsy after informed decision making. In the mpMRI targeted biopsy group, patients initially underwent a mpMRI. If it was normal, no biopsy was performed, and routine follow-up was continued. If the mpMRI showed a lesion, a targeted biopsy only was performed.  The primary outcome of the trial was the proportion of men with clinically significant prostate cancer (Gleason score >=3+4=7). The study was very pragmatic and demonstrated real-world experience. It included both academic and non-academic centers, both 1.5 T and 3 T MRIs were allowed, in the standard group, both TRUS and transperineal biopsies were allowed, and lastly in the targeted mpMRI biopsy, both visual and software fusion techniques were allowed. The results of the trial demonstrated that in the mpMRI targeted biopsy group and in the standard biopsy group the rate of diagnosis of clinically significant cancer was 38% and 26%, respectively, p=0.005. Furthermore, the rate of non-significant cancer diagnosed was lower in the mpMRI targeted biopsy group (9% vs. 22%, p<0.001). Importantly, 25% of men managed to avoid an unnecessary biopsy in the mpMRI targeted biopsy group.

The PROMIS study was a multicenter, paired - confirmatory cohort trial, comparing TRUS biopsy to mpMRI targeted biopsy using Likert score.2 In this study, the mpMRI had a higher sensitivity (93% vs. 48%) and negative predictive value (89% vs. 74%), but lower specificity than TRUS biopsy (41% vs. 96%). The sensitivity and negative predictive value of mpMRI depend on the definition of clinically significant prostate cancer. Most importantly, the PROMIS trial demonstrated that no high-risk tumors (Gleason Grade Group 3-5) were missed using the mpMRI targeted strategy biopsy. In a meta-analysis assessing the negative predictive values of mpMRI imaging in excluding prostate cancer at biopsy, a negative predictive value of 82% was shown for overall cancer detection, and 88% for clinically significant cancer.3

The next topic discussed was whether we should combine systematic and targeted biopsies. In a study comparing MRI/US fusion-guided biopsy with US-guided biopsy for the detection of prostate cancer, the fusion biopsy had 30% more significant prostate cancer diagnosis rate and 17% fewer insignificant prostate cancer diagnosis rate.4 This study showed that to detect one extra patient with high-risk prostate cancer, 200 patients needed to undergo additional systematic biopsies, and 17 new cases of low-risk prostate cancer needed to be diagnosed. Targeted mpMRI biopsies were demonstrated to be more accurate than a systematic biopsy and the combination of both systematic and targeted biopsy, in predicting intermediate and high-risk prostate cancer on prostatectomy specimens. The targeted biopsy had an area under the curve (AUC) (95% C.I) of 0.73 (0.66-0.79) compared to standard systematic biopsy, which had an AUC of 0.59 (0.52-0.67) and compared to the combination of both standard biopsies + targeted mpMRI biopsy having an AUC of 0.67 (0.6-0.74).

Despite the interesting advantages that mpMRI targeted biopsy strategy has to offer, it does have has some limitations worth mentioning. There are variations in the quality and interpretation of mpMRI. There is also variation in the accuracy of MRI-targeted biopsies, as it is operator dependent, and due to the difference between systems and targeting techniques. To date, almost all nomograms are based on DRE and template biopsies and not on mpMRI results. Lastly, there is also a need for a better definition of clinically significant prostate cancer.

In conclusion, there is level 1 evidence supporting the implementation of MRI-targeted biopsies as an initial strategy in patients with a clinical suspicion of prostate cancer. Systematic biopsies should be performed in several conditions: In patients that cannot undergo mpMRI, during the learning curve of mpMRI-targeted biopsy, in patients with a normal mpMRI and known risk factors (family history of prostate cancer, BRCA carriers, and high PSA density), and in patients with persisting clinical suspicion of prostate cancer despite previous negative (MRI-targeted). Combined targeted + systematic biopsies can increase the detection rate of clinically significant prostate cancer but come at the cost of moreover detection of insignificant prostate cancer, and significant tumors will still be missed.


Presented by: Professor Everaerts Wouter, Leuven, Belgium

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@GoldbergHanan at the 2nd EAU Update on Prostate Cancer  (PCa18)– September 14-15, 2018 – Milan, Italy

References:
1. Kasivisvanathan et al. NEJM  2018
2. Ahmed et al. Lancet 2017; 389:815
3. Moldovan PC. et al. Eur Urol 72 (2017) 250-266
4. Siddiqui MM et al. JAMA 2015