Prostate cancer (PCa) is the most common non-cutaneous malignancy in men, with more than 161,000 new cases expected to be diagnosed in the United States alone for 2017.1 Currently, the gold standard for initial PCa detection is the 12-core transrectal ultrasound-guided prostate biopsy (TRUS-B).2

The most pressing concerns with traditional TRUS-B involve the accuracy of making a PCa diagnosis and associated secondary procedure-related complications, including hemorrhage and sepsis. From a cancer diagnosis standpoint, TRUS-B is imperfect because overdiagnosis of clinically indolent cancers and underdiagnosis of biologically aggressive disease continue to be common events.3, 4  The recent application of multiparametric magnetic resonance imaging (MRI) to the prostate to identify areas of greater suspicion, combined with MRI/ultrasound fusion-targeted prostate biopsy, has mitigated some of the problems associated with cancer diagnosis, but issues with infectious complications remain. Up to 7% of patients who undergo TRUS-B suffer an infectious episode, and sepsis occurs in up to 3%.5 With emerging resistance to antimicrobials—particularly the commonly used fluoroquinolones—the incidence of infection after TRUS-B is expected to rise.6

The transperineal (TP) approach to prostate biopsy has recently been adopted at many centers as an alternative to TRUS-B and may be able to address some of these concerns. For example, TP may improve PCa diagnosis by allowing easier access to sample the entire prostate gland, particularly the anterior prostate.7 Moreover, reported rates of infectious complications associated with TP biopsy are exceedingly low, with hospital admissions for infection approaching zero in most accounts.8 Together, the potential for improved PCa diagnosis and reduced risk of complications elevates the importance of a structured investigation of the TP approach for prostate biopsy.

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Transrectal vs Transperineal Approach

One randomized trial and a meta-analysis have explored differences in cancer detection between TRUS-B and TP biopsy (Table 1).

Table 1. Prostate Cancer Detection and Complications Between TRUS-B and TP biopsy

Reference n Mean Age (y) Positive cores (%) Infection (%) Bleeding (%)
Hara et al.9 TRUS-B: 120
TP: 126
TRUS-B: 71.1±7.6
TP: 71.0±7.3
TRUS-B: 48.3
TP: 42.1
TRUS-B: 1.7
TP: 0
TRUS-B: 9.2
TP: 10.3
Loeb et al.12 TRUS-B: 9,241 TRUS-B: median
67.6 (54.6–76.6)
TRUS-B: 10 TRUS-B: 4.2 TRUS-B: 22–50
Raaikmaers et al.25 TRUS-B: 5,802 TRUS-B: NR TRUS-B: 22.8 TRUS-B: 3.5 TRUS-B: 22–50
Pepe et al.16 TP: 3000 TP: median 61.8
TP: 38.3 TP: 0.7 TP: 31.2
Grummet et al.8 TP: 245 TP: median 61-70 TP: 39 TP: 0 TP: NR
Merrick et al.23 TP: 46 TP: 63.3±9.8 TP: 67.4 TP: 0 TP: NR
Symons et al.26* TP: 409 TP: 63.3±0.8 TP: 56.7 TP: 3.2 TP: 50.4

TP: transperineal TRUS-B: transrectal ultrasound-guided biopsy NR: not reported
*TP saturation biopsy with mean 19.2±0.77 cores

Hara and colleagues randomized 226 patients to either TRUS-B or TP approach.9  After randomization, the cohorts were matched regarding patient age, PSA level, prostate volume, PSA density, and DRE findings. The overall cancer detection rate was similar: 48.3% (58/120) for TRUS-B and 42.1% (53/126) for the TP approach (P = 0.323). However, the authors did not stratify cancer detection based on contemporary definitions of clinical significance or define possible differences in Gleason grade/Grade Group results. Of note, in an earlier subgroup analysis of the first 200 patients in the study, Takenaka and colleagues reported that TP biopsy was more sensitive to diagnose transition zone tumors in patients with PSA levels of 4–10 ng/mL (10.7% vs 5.6%, P = 0.045).10 This difference was not reported in a later analysis.

Shen and colleagues performed a systematic review and meta-analysis of 7 studies (2,218 patients) to assess differences in cancer detection rate between TRUS-B and TP biopsy.11 Again, there was no difference in overall PCa detection rate between the TRUS-B (31.4%) and TP (25.7%) approach (P = 0.3). The lack of difference in PCa detection persisted in subgroup analyses stratified by PSA level.

Taken together, these studies suggest that the TRUS-B and TP approaches are equivalent in overall PCa detection rate. A major limitation thus far is a lack of information regarding any possible difference in detection of clinically significant PCa (eg, Grade Group 2 or higher) between the 2 approaches.


Given the similar PCa detection rate between TRUS-B and TP biopsy, a reduction in procedural risk could justify greater utilization of the TP approach. To date, randomized, controlled trial data suggest little difference in overall complications between the approaches.9, 10 Non-randomized data, however, suggest a reduction in infectious complications with TP biopsy.

The reported risk of any infection after TRUS-B biopsy is 5%–7%, and more severe infections requiring hospitalization range from 1%–3%.5 In the European Randomized Study of Screening for Prostate Cancer, post-procedural fever was reported in 392 patients (4.2%) and resulted in 78 (0.8%) hospital admissions.12 Various strategies have been adopted aiming to reduce infectious complications after TRUS-B, including rectal swab culture-directed antibiotic prophylaxis.5 In a pilot prospective cohort, using a culture-directed antibiotic prophylaxis approach resulted in fewer infectious complications and a cost reduction of $4,500 per avoided infection.13  Given the recognized increasing rates of fluoroquinolone-resistant organisms,14 however, it is reasonable to predict that rates of post-biopsy infectious complications will increase. Moreover, the FDA has recently changed the safety labeling for fluoroquinolones, recommending that they should not be used for uncomplicated urinary tract infections (UTIs) unless there are no appropriate alternatives.15 Thus, appropriate stewardship of antibiotics is of utmost importance.

Infectious complications associated with TP biopsy are less prevalent. In the largest reported series to date (3000 patients), Pepe and Aragona reported post-procedural fever in 17 (0.5%), and UTIs requiring hospitalization in 21 (0.7%).16 Importantly, no patients experienced an infection meeting sepsis criteria. Grummet and colleagues presented a review of patient admissions for sepsis after TP biopsy;8 of 6,609 patients, only 5 (0.076%) cases of sepsis were reported. Given similar cancer detection rates between TRUS-B and TP biopsy and markedly lower risk of infectious complications associated with TP  biopsy, the latter may deserve more consideration than it currently enjoys.

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Transperineal Technique and Patient-Reported Outcomes

One of the major criticisms of the TP biopsy technique is the need for general anesthesia.17  Indeed, the common template-based, TP biopsy approach has been described with the patient under general anesthesia.7, 18 For example, the gold standard to which MRI-US fusion targeted prostate biopsy was compared in the PROMIS study was a transperineal, template-based biopsy performed under general anesthesia.7 Similarly, Hansen and colleagues recently reported their experience with MRI-US fusion supported transperineal prostate biopsy using general anesthesia.18

General anesthesia is not mandatory for TP biopsy, however, and procedures under local anesthesia have been reported.  Bass and colleagues reported on outpatient TP biopsy in 181 patients.19 Men receive tramadol 100 mg orally and topical 2% diltiazem ointment to relax the anal sphincter 1 hour prior to the procedure. Twenty milliliters of lidocaine-infused gel are inserted into the rectum. The perineal skin is anesthetized with 0.5% bupivacaine and 1:200,000 epinephrine. A peri-prostatic block is then performed transperineally with a 50:50 mixture of 10 mL of 0.5% bupivacaine and 10 mL of 1% lidocaine. The biopsy procedure is performed after allowing 2 minutes for the local analgesia to take effect.

Further, several variations on local anesthetic techniques have been described including subcutaneous perineal nerve block, pudendal nerve block, periapical triangle block, and prostatic apex block.20 Iremashvili and colleagues completed a randomized controlled trial assessing the tolerability of peri-prostatic block versus peri-prostatic block with pudendal nerve block.21 Patients receiving the pudendal nerve block reported significantly better pain control throughout probe insertion, biopsy punctures, and at 1 hour after biopsy.

Local anesthetic techniques result in acceptable patient-reported tolerability outcomes. Bass and colleagues reported that 89% of men were “not dissatisfied” with their procedure and would recommend it to others.19 Smith and colleagues assessed the tolerability of outpatient prostate biopsy in 50 consecutive patients using visual analog scales (VAS).22 On a scale from 0-10, in which 0 represents no pain and 10 represents the worst pain imaginable, mean VAS scores for probe insertion (3.08±1.64) local anesthetic injections (3.29±1.64), and biopsies (2.88±1.28) were within acceptable ranges. Similarly, Merrick et al. recorded mean VAS scores for 46 men after instillation of local anesthesia (4.2 ±1.8) and after outpatient transperineal prostate biopsy (3.0±1.4).23 Thus, it appears that an acceptable patient experience can be provided in the outpatient setting with appropriate expertise.

Traditionally, TP biopsy has been performed using a brachytherapy grid and stepper.19 Free-hand techniques have been reported to eliminate the need for a grid and stepper, although these techniques are somewhat difficult to master.24 A guided TP technique using the recently developed PrecisionPointTM Transperineal Access System (Perineologic, Cumberland, MD) has shown some promise in facilitating the transition from a brachytherapy grid and stepper to a free-hand approach that can be more readily performed in the outpatient setting (Figure 1). Early results with this device are encouraging, enabling TP biopsy under the same outpatient conditions currently used for TRUS-B.


Cancer detection rates for TRUS-B and TP prostate biopsy are similar, and either approach can be combined with MRI to enable more accurate targeting of suspicious lesions. A major advantage of the TP approach is a reduction in post-procedural infectious complications. The overall sepsis rate of 0.08% using the TP approach is an order of magnitude lower than the 1%–3% rate seen with TRUS-B. As bacterial resistance patterns emerge, antibiotic stewardship will become increasingly important. Moreover, several outpatient TP biopsy series using local anesthesia alone have recently been reported abrogating the often criticized requirement for general anesthesia. Given lower rates of infectious complications and greater feasibility of an office-based procedure, we expect that TP prostate biopsy will be increasingly adopted as the preferred approach for PCa evaluation.

Benjamin T. Ristau, MD, MHA, is an Assistant Professor of Surgery at UConn Health in Farmington, Connecticut.

David Chen, MD

David Y.T. Chen, MD, is an Associate Professor of Urologic Oncology at Fox Chase Cancer Center in Philadelphia.


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