MRI-targeted prostate biopsies guided by micro-ultrasound and a transperineal approach

The debate on MRI-targeted prostate biopsies is active. The very recent meta-analysis by a Chinese university 1 evaluates the respective roles of targeted and systematic biopsies in the diagnosis of prostate cancer in an analysis of 39 studies including 4000 patients, with data collection up the end of December 2018. In patients with an abnormal MRI (PI-RADS score>2), the combination of targeted and systematic biopsies resulted in a detection rate of significant cancers (Gleason score >3+3) of 45%, higher than that of targeted or systematic biopsies alone. With targeted biopsies only, the detection rate of significant cancers dropped by 13%, but by 25% with systematic biopsies only. The logical conclusion of the meta-analysis is therefore that the targeted + systematic biopsy scheme should be maintained.

The reason may be the lack of accuracy of the targeting. The imaging modality used to guide the needle pathway should ideally “see” the target at the time of biopsy, avoiding the established limitations of TRUS-MRI softwares (image fusion) . A direct visualisation is possible if real-time MRI guidance is used 2. It is also possible to use a conventional endorectal ultrasound probe equipped with a very high-quality B mode. This material allows to detect the majority of PI-RADS 4 or 5 lesions in the peripheral zone and the biopsy is then performed with real-time visual guidance 3. It is now even possible to use an ultrasound transducer equipped with a 29MHz linear array (Exact Imaging, Canada), also known as micro-ultrasound 4,5. This material provides a spatial resolution never achieved until now for the prostate. The 14-29 MHz bandwidth allows for a depth of exploration of 50mm. All significant tumors detected on MRI (figure 1) are visible with this equipment. (Cornud et al, submitted for publication). A navigation fusion system is available if the tumor is not well delineated (figure 1).

it is highly probable that systematic biopsies in addition to targeted biopsies are recommended to avoid missing the target, a legitimate risk given the established targeting errors of fusion biopsies. However, it becomes desirable in 2020 to consider an alternative to image fusion by using either in bore MRI- either micro-ultrasound guidance to improve the accuracy of a targeted biopsy and by adapting the site of the biopsies (target and margin around the target).  This strategy may allow to discard systematic biopsies.

It should be noted that this meta-analysis is published at a time where the transrectal route is increasingly being questioned, given the septic risk it entails. Limiting transrectal biopsies to the most suspicious targets (PI-RADS 4 or 5), a common-sense strategy adopted in current practice by many practitioners, is probably a factor which may decrease the risk of post-biopsy infection 6. Conversely, PI-RADS 3 lesions, when defined by centers with a high volume of prostate MRI reading, have a positive biopsy rate of 12% 7, i.e. barely higher than that observed in PI-RADS 2 category. Targeted biopsies only are therefore not appropriate and biopsy decision making is actually often not triggered by MRI findings, but by extra-MRI factors, such as a PSA density >0.15. Systematic biopsies may be then necessary, to pick up the 5-10% Gleason 7 tumors (mostly small volume 8 and small grade Gleason grade contingent lesions9) which remain undetectable by MRI. The septic risk of the transrectal approach has been increasingly denounced these past years. More than one million prostate biopsies are performed in Europe and the United States every year. Fever or chills are observed in more than 10% of cases and a severe infection in 1-2% 10. One case of death has been reported in a Norwegian study 11, which warned that the resistance to antibiotics steadily increased and predicted that it will quadruple in the coming years. For some authors, the transrectal route is becoming untenable 11 and the routine use of rectal culture swabs prior to any transrectal biopsies is strongly encouraged to detect a quinolone-resistant germ 10.

The alternative is the transperineal route, initially used under general anesthesia to perform saturation biopsies (one core every 5 mm), before the high predictive value of mp-MRI was established. Local anesthesia is now possible for these biopsies 1 (figure 2), which can be done with conscious sedation, or even for some authors with local anesthesia only. Their major advantage is the absence of infection, and the prophylaxis is done by IV injection of a first generation of cepaholosporin 30 mn before the biopsy, avoiding the risks of quinolone resistance. The transperineal route is also more efficient for the diagnosis of anterior and apical cancers 12.

All these reasons explain why it can be expected that the transperineal approach will gain a more widespread acceptance in a short future, especially if systematic biopsies are maintained.

References

  1. Tu X, Liu Z, Chang T, et al: Transperineal Magnetic Resonance Imaging-Targeted Biopsy May Perform Better Than Transrectal Route in the Detection of Clinically Significant Prostate Cancer: Systematic Review and Meta-analysis. Clin Genitourin Cancer 17:e860-e870, 2019
  2. Barral M, Lefevre A, Camparo P, et al: In-Bore Transrectal MRI-Guided Biopsy With Robotic Assistance in the Diagnosis of Prostate Cancer: An Analysis of 57 Patients. AJR Am J Roentgenol 213:W171-W179, 2019
  3. van de Ven WJ, Venderink W, Sedelaar JP, et al: MR-targeted TRUS prostate biopsy using local reference augmentation: initial experience. Int Urol Nephrol 48:1037-45, 2016
  4. Lughezzani G, Saita A, Lazzeri M, et al: Comparison of the Diagnostic Accuracy of Micro-ultrasound and Magnetic Resonance Imaging/Ultrasound Fusion Targeted Biopsies for the Diagnosis of Clinically Significant Prostate Cancer. Eur Urol Oncol 2:329-332, 2019
  5. Ghai S, Eure G, Fradet V, et al: Assessing Cancer Risk on Novel 29 MHz Micro-Ultrasound Images of the Prostate: Creation of the Micro-Ultrasound Protocol for Prostate Risk Identification. J Urol 196:562-9, 2016
  6. Grummet J, Pepdjonovic L, Huang S, et al: Transperineal vs. transrectal biopsy in MRI targeting. Transl Androl Urol 6:368-375, 2017
  7. Kasivisvanathan V, Rannikko AS, Borghi M, et al: MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med, 2018
  8. De Visschere PJ, Naesens L, Libbrecht L, et al: What kind of prostate cancers do we miss on multiparametric magnetic resonance imaging? Eur Radiol 26:1098-107, 2016
  9. Delongchamps NB, Lefevre A, Bouazza N, et al: Detection of significant prostate cancer with magnetic resonance targeted biopsies–should transrectal ultrasound-magnetic resonance imaging fusion guided biopsies alone be a standard of care? J Urol 193:1198-204, 2015
  10. Thurtle D, Starling L, Leonard K, et al: Improving the safety and tolerability of local anaesthetic outpatient transperineal prostate biopsies: A pilot study of the CAMbridge PROstate Biopsy (CAMPROBE) method. J Clin Urol 11:192-199, 2018
  11. Johansen TEB, Zahl PH, Baco E, et al: Antibiotic resistance, hospitalizations, and mortality related to prostate biopsy: first report from the Norwegian Patient Registry. World J Urol, 2019
  12. Covin B, Roumiguie M, Quintyn-Ranty ML, et al: Refining the risk-stratification of transrectal biopsy-detected prostate cancer by elastic fusion registration transperineal biopsies. World J Urol 37:269-275, 2019

Figure 1 : 67 y/o man. PSA level : 7 ng/ml. Anterior TZ hyposignal (asterisk, a-b) with marked restricted diffusion (asterisk, c), visible on micro-ultrasound (white arrows, d) corresponding to a Gleason score 3+4 carcinoma on micro-ultrasound guided targeted biopsies.The blue tag on the left upper corner (d) is obtained by image fusion, which can be helpful if the anterior lesion is not well seen on micro ultrasound.

Figure 2 :Transperineal systematic biopsies in a 65 y/o man with a raising PSA. MRI showed no focal lesion. Local anesthesia (arrow, a), is first done subcutaneously covering a horseshoe shaped area (dotted line). The needle guide (arrow, b) is then positioned and used for the periprostatic anesthesia (arrow, c). Local spread of the lidocaine (asterisk, c) is followed in real-time. The needle biopsy (d) follows a cranio-caudal route when the biopsy device is activated, allowing for an optimal amount of PZ or TZ sampled tissue, when compared to a transrectal biopsy. A standard transperineal biopsy scheme includes 11 cores and can be increased to 20 cores if the TZ needs to be sampled.