This manuscript outlines the steps for performing a micro-ultrasound-guided transperineal prostate biopsy under local anesthesia.
Prostate cancer is the most common solid malignancy in men and requires a biopsy for diagnosis. This manuscript describes a freehand micro-ultrasound guided transperineal technique performed under local anesthesia, which maintains accuracy, keeps patients comfortable, has low adverse events, and minimizes the need for disposables. Prior micro-ultrasound-guided transperineal techniques required general or spinal anesthesia. The key steps described in the protocol include (1) the placement of the local anesthesia, (2) micro-ultrasound imaging, (3) and the visualization of the anesthetic/biopsy needle while uncoupled from the insonation plane. A retrospective review of 100 patients undergoing this technique demonstrated a 68% clinically significant cancer detection rate. Pain scores were prospectively collected in a subset of patients (N = 20) and showed a median procedural pain score of 2 out of 10. The 30 day Grade III adverse event rate was 3%; one of these events was probably related to the prostate biopsy. Overall, we present a simple, accurate, and safe technique for performing a micro-ultrasound-guided transperineal prostate biopsy.
Prostate cancer is the most common solid malignancy among American men, with 268,000 projected diagnoses in 20221. The diagnosis of prostate cancer requires a prostate biopsy, which is traditionally performed by passing a biopsy needle through the rectal mucosa (transrectal) into the prostate. The needle guidance follows a systematic "blind" template, as conventional ultrasound cannot differentiate cancer from benign tissue2. In the United States, over 1 million such biopsies are performed annually3,4.
Over the last decade, two significant advances in imaging and techniques have improved safety and accuracy. First, increasing the use of transperineal biopsies to avoid the rectal mucosa has decreased the risk of sepsis without needing antibiotics5,6. Second, the use of MRI and micro-ultrasound (Micro-US) have improved cancer detection rates compared to biopsy with conventional (5 MHz) ultrasound guidance5,7,8,9.
Micro-US utilizes 29 MHz acoustic waves, improved piezoelectric crystal density, and novel wave processing to achieve a spatial resolution of 70 µm compared to around 200 µm for a conventional ultrasound8. A grading system using a 5-point Likert scale (Prostate Risk Identification Using Micro-Ultrasound, PRI-MUS), is used to quantify the risk of prostate cancer in micro-ultrasound lesions10. Biopsy core and PRI-MUS lesion locations are tracked relative to the midline using an accelerometer located in the handle of the Micro-US probe (ExactImaging, Markham, ON). The ability to track biopsies enables the 3D reconstruction of prostate cancer locations. Precision cancer treatments such as focal therapy and radiation boosting are enabled through the spatial information gained by tracked cores.
To date, no published techniques enabling micro-ultrasound-guided transperineal prostate biopsy under local anesthesia can also retain the spatial orientation of the cores and lesions. This manuscript aims to delineate such a technique.
The methods described are based on experience at the University of Florida (UF). The protocol and acquisition of data were approved by the University Institutional Review Board (IRB). Indications for prostate biopsy included a suspicious digital rectal exam (DRE), prostate-specific antigen (PSA) elevation, or another biomarker abnormality (i.e., 4K, ExoDx). The protocol is described for a right-handed surgeon.
1. Micro-ultrasound probe preparation
2. Patient positioning and anesthesia
3. Micro-ultrasound diagnosis
4. Diagnostic evaluation
5. Prostate anesthesia
6. Prostate biopsy
7. Procedure end
A retrospective analysis of our prospectively maintained database from September 2021 to June 2022 (IRB202200022) is described. Clinically significant prostate cancer (csPCa) was considered ≥Grade Group 2 (Gleason 3 + 4 = 7) prostate cancer. The cancer detection rate (CDR) was calculated as ≥GG2/total patients. Pain scores were evaluated on a 1-10-point Likert scale at baseline, at local anesthesia placement, at rectal probe insertion, and during the biopsy. Adverse events were discussed with patients at 2 weeks following the procedure, and chart review-captured events were documented within 30 days of the biopsy. Adverse events were graded using the CTEP (Cancer Therapy Evaluation Program) grade and attribution guide.
We identified 100 patients who underwent Micro-US guided, clinic-based transperineal biopsy under local anesthesia. In this study, the per-patient CDR was 68%. The CDR varied depending on each lesion's PI-RADS (Prostate Image Reporting and Data System) and PRI-MUS scores (Table 1).
Pain scores were available amongst a later subset of patients (N = 20). The median (IQR) pain scores were 0 (0, 1) at baseline, 2 (1, 4) during the administration of local anesthesia, 2 (1, 5) during the transrectal probe placement, and 2 (0, 5) during the prostate biopsy.
Adverse events were relatively rare, with a 3% incidence of Grade III adverse events (Table 2). There were no Grade IV or Grade V events. The Grade II events primarily involved the new prescription of alpha-blockers to alleviate a slowing urinary stream. As mentioned above, the patients were screened for symptoms before the biopsy. Grade III events involved the hospitalization of three patients. As per the CTEP attribution guide, one hospitalization due to symptomatic hypotension was probably related to the prostate biopsy secondary to lidocaine absorption. The patient experienced a spontaneous resolution of symptoms within 12 h of monitoring. Two additional patients were hospitalized (mechanical fall and altered mental status) within 30 days of the biopsy. They were incidentally found to have non-septic and non-symptomatic UTIs, possibly related to the biopsy. Aside from these specific patients mentioned, there were no sepsis, prostatitis, cystitis, or other infection cases.
Figure 1: Micro-ultrasound setup, biopsy tray, and needle placement. (A) The procedure room setup with the ExactVu Machine placed on the surgeon's right. (B) Biopsy table including (a) betadine-soaked 4 cm x 4 cm gauze pads, (b) 10 mL of 2% lidocaine gel, (c) 1% lidocaine with 1:100,000 epinephrine distributed with 2 mL of 8.4% sodium bicarbonate solution (1 mL of NaHCO3: 10 mL of lidocaine) in 2x 20 mL syringes with a 2 inch 25 G needle and a 6 inch 20 G needle, (d) a 14 G angiocath or coaxial metal needle, (e) a biopsy gun, (f) foam biopsy pads, and formalin containers. (C) The hand position for performing the diagnostic sweep. Note that the left hand supports the upward pressure on the prostate, while the right hand rotates the probe. (D) The coaxial needle or angiocatheter position: 10 o'clock for the right-sided prostate, and 2 o'clock for the left-sided prostate (not shown). Please click here to view a larger version of this figure.
Figure 2: Demonstration of the prostate anatomy and biopsy. (A) Visualization of the levator ani and periapical triangle; both are important structures to anesthetize for the successful implementation of this technique. (B) Demonstration of a PRI-MUS 5 lesion, anatomically concordant with the pre-biopsy MRI. (C) Visual confirmation of the biopsy needle traversing the target. Please click here to view a larger version of this figure.
Figure 3: Systematic biopsy template for the proposed technique. This template is based on the template available in the Michigan Urologic Surgery Improvement Collaborative (MUSIC)14. However, this template is an improvement in three regards. (i) Increased anterior zone sampling (4 cores versus 2 cores), (ii) Greatly improved visual display of the core location using a 3D model, and (iii) modified core nomenclature to improve usability. In this protocol, systematic biopsies are taken after the ROI biopsy within imaging negative (PRI-MUS ≤ 2) tissue. Please click here to view a larger version of this figure.
PI-RADS 5 | PI-RADS 4 | PI-RADS 3 | |
PRI-MUS 5 | 95% (n = 20) | 80% (n = 15) | 100% (n = 1) |
PRI-MUS 4 | 100% (n = 1) | 69% (n = 13) | 75% (n = 4) |
PRI-MUS 3 | 0% (n = 0) | 33% (n = 3) | NA |
Table 1: Detection of clinically significant prostate cancer stratified by PI-RAD and PRI-MUS scores. Clinically significant prostate cancer detection rate (CDR) among patients with both MRI and micro-ultrasound available at the time of biopsy. The CDR is stratified by the PI-RADS (column) and PRI-MUS scores (row). The number of patients meeting these criteria is recorded in parentheses.
CLAVIEN DINDO GRADE | INCIDENCE |
GRADE I | 4% (n = 4) |
GRADE II | 5% (n = 5) |
GRADE III | 3% (n = 3) |
GRADE IV | 0% (n = 0) |
GRADE V | 0% (n = 0) |
Table 2: Percentage of patients experiencing adverse events by grade. Percentage of patients with an adverse event within 30 days of the prostate biopsy. Note that Grade III adverse events were hospitalizations for non-septic events, one of which was probably related to the biopsy and two of which were possibly associated with the biopsy.
This manuscript details the procedure and results for Micro-US guided, freehand, transperineal prostate biopsy under local anesthesia. This is the first description of a technique that preserves the biopsy core location and patient comfort. In our experience, the procedure is accurate, well tolerated, and has minimal adverse events.
Notably, there were no reported cases of sepsis or prostatitis despite the lack of prophylactic antibiotics. The results from the sample used here corroborate the findings and complication rate of the NORAPP trial, which did not find a benefit of prophylactic antibiotics in transperineal biopsy6.
The critical steps of the procedure are as follows. The disinfection and anesthesia noted in step 2.6 and section 5 are the key components for reducing the infection rates by traversing the perineum rather than the rectal wall while maintaining patient comfort. Section 4 delineates the ROIs for biopsy targets, allowing for fewer cores to be taken while effectively sampling the problematic areas of the prostate.
Transperineal biopsy has gained popularity compared to alternative methods given the zero rates of sepsis15,16, the accuracy of sampling anterior tumors, the antibiotic stewardship, and guideline recommendations17,18. Simultaneously, Micro-US is being recognized as an accurate cancer imaging modality, simple fusion platform, and independent imaging biomarker9,19. Prior Micro-US guided transperineal techniques reported an excellent CDR of 42%; however, this technique utilized a needle guide to align the needle and insonation plane. While using a guide improves the learning curve, it likely confines biopsy to the operating room to allow for the use of general anesthesia, as each biopsy puncture enters through a new site20. We report a CDR of 68%, demonstrating that this free-hand technique has comparable accuracy to the use of a needle guide.
Our technique's accuracy, tolerability, and minimal adverse events must be interpreted within certain limitations. Approximately 3 h of hands-on practice on a simulator or phantom is required to locate and direct the biopsy needle. Additional time may be required to learn the Micro-US image interpretation. Performing targeted plus systematic biopsies can result in 17 or more biopsy cores and require up to 30 min of procedure time. While we report excellent cancer detection rates, the success of this technique partly relates to our practice of omitting the prostate biopsy in patients with a <15% calculated risk of csPCa21. Finally, the systematic biopsy template used in this study samples the highest-risk areas of the prostate but has never been compared to other transperineal biopsy templates. Despite these limitations, this technique has several advantages, most notably the ability to perform the procedure in a clinic-based environment. Additionally, the position tracking of the micro-US probe allows for the 3D reconstruction of the cancer locations for use when performing surgical extirpation, radiation boosting, or focal therapy.
In conclusion, Micro-US represents a recent improvement in prostate biopsy. We demonstrate a transperineal approach that can be implemented in the clinic under local anesthesia. While further evaluation and improvements to the diagnostic capacity of Micro-US are warranted, surgeons adopting this technique will find it simple to implement, accurate, and safe.
The authors have nothing to disclose.
None.
14 ga Angiocatheter | BD Angiocath | BD382269 | |
Aquasonic | Parker Labs | Aquasonic 100 | |
Biopsy Needle | Bard | MaxCore | |
Biopsy Sponge 2 mm x 25.4 mm x 30.2 mm | McKesson | 1019107 | |
ExactVu Micro-Ultrasound Machine | ExactImaging | ||
ExactVu Micro-Ultrasound Probe (EV29L) | ExactImaging | ||
Guaze Sponge McKesson Cotton 12-Ply 4'' x 4'' | McKesson | 762703 | |
Hypodermic Needle 25 G 1.5 inch | McKesson | 42142523 | |
Lidocaine 1% with Epinephrine 1:100,000 | NA | ||
Lidocaine 2% Gel, 20 mL | URO-Jet | 76329301505 | |
Probe Cover | ExactImaging | ||
Skin Prep Solution betadine (10%) | McKesson | 1073829 | |
Spinal Needle 20 G, 6 inch | McKesson | 992546 | |
TruGuide | Bard | C1616A |
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