Transrectal Ultrasound Guided Biopsy of the Prostate (2019)

5. PATIENT ASSESSMENT AND PREPARATION

5.1 Indications

The need for an initial prostate biopsy is based on PSA level, familial risk, and suspicious DRE or imaging. Age, potential comorbidity, and therapeutic consequences should also be considered and discussed beforehand. A single limited PSA elevation alone should not prompt immediate biopsy. PSA level should be verified after a few weeks using the same assay under standardised conditions (i.e., no ejaculation, manipulations, and urinary tract infections) in the same laboratory. [38,39]

Despite this, for men with PSA 4–10 ng/ml, the chance of finding cancer is ~25% but many of these tumours are insignificant. Risk stratification is a potential tool for reducing unnecessary biopsies. [40] Risk calculators may be useful in helping to determine (on an individual basis) what the potential risk of cancer may be. Several tools developed from cohort studies are available from:

• the Prostate Cancer Prevention Trial Risk Calculator Version 2.0 (PCPTRC 2.0) 
  http://myprostatecancerrisk.com/;
• the European Randomized Study of Screening for Prostate Cancer: 
  http://www.prostatecancer-riskcalculator.com/seven-prostate-cancer-risk-calculators

An updated version was presented in 2017, including prediction of low and high risk, based on the International Society of Urological Pathology (ISUP) grading system and presence of cribriform growth in histology. [41]

Prior imaging with MRI for detecting prostate cancer remains controversial but evidence from the PROMIS and PRECISION studies [42,43] has suggested that upfront multi-parametric MRI (mpMRI) with targeted biopsy of abnormal lesions is significantly better for detecting clinically important prostate cancer compared to TRUS biopsies, and reduces the number of insignificant cancers detected.

Prostate biopsy can be performed by either the transrectal or transperineal approach. Xue et al. (2017) have shown that cancer detection rates are comparable between the two approaches, when performed without prior MRI. [44]

The indications for repeat biopsy are:

• rising and/or persistently elevated PSA;
• atypical small acinar proliferation (i.e., atypical glands suspicious for cancer), 31–40% risk [45];
• extensive (multiple biopsy sites, i.e., ≥3) high-grade prostatic intraepithelial neoplasia, 30%. [46]; and
• active surveillance.

5.2 Patient information pre-biopsy (PICO 3)

Giving information to patients who are undergoing TRUS biopsy is crucial as it can lower anxiety before and after the procedure. [47] Patients who feel inadequately informed experience more adverse effects than those that are well prepared. [48]

A patient information leaflet (PIL) should be given to inform every patient before TRUS biopsy. Although there are wide variations in the content of the information in different centres/hospitals [49], it is agreed that PILs can play a key role in improving patients’ experience and manage their expectations about:

• significance or rationale of the procedure;
• procedure explanation: number of cores, analgesia, staff who will carry out the procedure;
• potential adverse effects;
• possible complications and duration;
• how to manage complications; and
• hospital contact numbers. [48]

Unfortunately, however, most of the PILs about TRUS biopsy poorly adhere to the guidelines and are difficult for patients to understand. [50] A PIL without any explanation from the health care giver is insufficient. [51]

Increasingly, an important source of information for patients is the Internet, but there is a wide variance in quality of information on the Web about TRUS biopsies. The health care giver should be aware of that and can be a trusted guide for patients to find reliable medical websites for more information. [50,52]

Health care providers should also be aware that written information on prostate cancer (both on websites and in leaflets) often requires a higher level of understanding than that of the average adult and therefore may present a barrier. [50]

5.3 Pre-investigations and prophylaxis

Patient selection
Appropriate patient selection is important when considering prostate biopsy. Pre-existing comorbidity, medication and infection risk should be assessed both in the context of carrying out the biopsy and considering whether the patient is fit to undergo any treatment if cancer were to be diagnosed. Patients should be questioned to elicit any high-risk behaviour.

Prophylactic antibiotics
Oral or intravenous antibiotics are recommended. Quinolones are the drugs of choice, with ciprofloxacin being superior to ofloxacin. [53]

Antimicrobial prophylaxis should be used on the basis of patients’ existing risk factors. In patients with one or more of these risk factors, practitioners should consider utilisation of targeted prophylaxis or augmented antimicrobial therapy. [54–56]

When deciding on the choice of antibiotic, dosage and timing, individual risk factors and local policies and pathways should be taken into account including regional and local antibiotic resistance patterns. Increased quinolone resistance is associated with a rise in severe post-biopsy infection. [57,58]

Assessment of the urinary tract
Pre-biopsy assessment of urinary symptoms is important to exclude risk of urinary retention and current/active urinary infection. [59]

Perineal swabs and antimicrobial resistance
The evidence for perineal swabbing prior to prostate biopsy is weak and conflicting. [60–62] The evidence supporting pre-biopsy swabbing appears to depend on the patient group. All of the reviewed publications support rectal swabs in high-risk patient groups, that is: patients at high risk of infection; patients with recurrent or recent urinary tract infection treated with antibiotics (in the last 6 months); patients recently treated with antibiotics; and patients who have recently travelled through Asia. [63]

Urinary flow
The risk of urinary retention after biopsy is considered low in most documented series. Overall, the risk is 0.2–0.8%. [64,65] However, stratifying the potential risk of retention before biopsy is a sensible approach through the use of the International Prostate Symptom Score, flow-rate and post-void residual measurement. Patients at highest risk should be treated with an α-blocker and/or laxatives if there is evidence of chronic constipation. [66,67]

Urinary infection
The evidence for collection of mid-stream specimen urine culture over urinalysis is strong and is documented in the 2016 EAU Guidelines on Urological Infections. [68]

Where evidence of bacteriuria is confirmed prior to urological procedure, exacerbation by prostate biopsy can lead to life-threatening sepsis if untreated. [55,69] Patients with symptomatic urinary infections should be deferred until treated.

If a confirmed infection results in elevated PSA level, the biopsy should be deferred and the (urinary) infection treated, and repeat PSA test may be recommended on discussion with the medical team.

Recent antibiotic use
Recent antibiotic use prior to biopsy has also been shown in several studies to increase the rate of infectious complications, mainly due to drug-resistant bacteria. [70] This was most acutely demonstrated in the quinolone-resistant group. [71] The increased infection risk of patients with prior antibiotic use is relevant for a period of 6 months prior to biopsy. [56]

Recent travel
Several studies have alluded to the increased risk of infection due to recent travel, which is significantly higher in people that have travelled to Southeast Asia and India. [63]

Recent hospitalisation
Hospitalisation within the month preceding biopsy is another known risk factor. [54] Kamdar et al. (2008) further found that 75% of patients who developed post-biopsy bacteraemia were either health care employees or had a relative working in health care and living within their household. [72]

Diabetes
Some studies have demonstrated associations between patient comorbidity and infection risk after prostate biopsy. Diabetes in particular confers an increased risk of febrile and infectious complications. [54,73] Practitioners may want to consider delaying prostate biopsy until glycaemic control is adequate; however, there have been no published studies on this measure.

MRI
Correlation with radical prostatectomy shows that mpMRI, associated with T2-weighted imaging with at least one functional imaging technique (diffusion weighting, dynamic contrast enhancement, or H1-spectroscopy), has good sensitivity for the detection and localisation of prostate cancer with GS >7. [74]

As a result, mpMRI is increasingly performed prior to biopsy, with incorporation of additional targeted biopsy of suspicious lesions. Such biopsies can be obtained through cognitive guidance, US/MR fusion software, or direct in-bore guidance. Current literature does not show clear superiority of one technique over the others. [75]

It has been shown that MRI-targeted biopsies improve detection of clinically significant prostate cancer in the repeat biopsy setting. [76]

However, single-centre RCTs performed in biopsy-naïve men provided contradictory findings as to whether the addition of MRI-targeted biopsies to systemic biopsies improved the detection of either prostate cancer or clinically significant prostate cancer. [77–79]

The recent multicentre RCT PRECISION study [42] showed that MRI before biopsy and targeted biopsy was superior to standard biopsy alone. The question remains: is the combination of MRI-targeted biopsy plus systemic biopsy better than targeted biopsy alone.

Rectal preparation
Since the bacteria responsible for prostate-biopsy-related infection primarily originates in the rectum, various rectal agents have been evaluated for their ability to reduce bacterial load and risk of infection.

Enemas: pre-biopsy enema has demonstrated limited benefit in reducing post-biopsy infection rate [80], with one study suggesting that enemas cause local rectal mucosal irritation and a subsequent increased risk of bacterial inoculation. [81]

Rectal cleansing: povidone–iodine solution (a widely available and cost-effective agent) has been studied as a potential rectal cleansing agent. Review of the literature is contradictory with most studies non-blinded or retrospective; however, there is some suggestion that high-risk patients may benefit. [61,82,83]

Methicillin-resistant Staphylococcus aureus (MRSA)
Testing for MRSA is not routinely recommended before prostate biopsy, unless a patient is at high risk. Positive MRSA infection does not affect the decision to carry out a biopsy; however, it may affect the use of antibiotics before or after the biopsy. Please refer to any local infection control guidelines.

Anti-aggregants and anti-coagulants (PICO 2)
Anti-coagulant and anti-aggregant drugs eliminate or reduce the risk of blood clots, using different mechanisms. However, both increase the risk of bleeding.

Common anti-coagulants include: heparin, warfarin (Coumadin), rivaroxaban (Xarelto), dabigatran (Pradaxa), apixaban (Eliquis), edoxaban (Savaysa), enoxaparin (Lovenox) and fondaparinux (Arixtra).

Common anti-aggregant drugs include: aspirin, clopidogrel (Plavix), ticagrelor (Brilinta), prasugrel (Effient), dipyridamole, dipyridamole/aspirin (Aggrenox), ticlodipine (Ticlid), eptifibatide (Integrilin).

The systematic review of the papers defining safe anti-coagulation and anti-platelet levels in TRUS biopsy is incomplete and does not reflect recent changes in prescribing patterns. However the following tables detail both risk groups and current evidence in relation to urological surgery (TRUS biopsy where available).

Risk groups
Anti-coagulants

Determining a patient’s thrombotic risk (i.e. of stroke or venous thromboembolism; VTE) if anti-coagulants are stopped is not straightforward and local guidelines should be used where available.

Risk categories of patients using anti-coagulants

This simple chart (Table 5) outlines risk categories as defined by the UK Pharmacy Association (2016). However local guidelines should be followed in regards to the requirements and dose of bridging therapies, for example, low-molecular weight heparin.

Table 5. Thrombotic risk categories of patients using anti-coagulants

[84]

Anti-aggregants
Patients on anti-aggregant therapy for secondary stroke prevention, especially after a recent stroke should continue with aspirin. Withdrawal of anti-aggregants should be avoided within 12 months of patients undergoing drug-eluting or bare-metal stent placement. If biopsy is required, a cardiology opinion should be sought for bridging therapy guidance, and where there are local guidelines, these should be preferentially followed.

Guidance on use of anti-coagulant, anti-platelet and anti-thrombotic agents pre-biopsy

The following tables give guidance on the common anti-coagulant, anti-platelet and anti-thrombotic agents with respect to when/if they should be stopped pre-biopsy.

Anti-coagulants
Patients in the high-risk group, may require a bridging treatment to their anti-coagulant therapy. Please discuss this with the patient’s prescriber or follow local hospital guidelines.

Table 6. Which anti-coagulants should be stopped pre-biopsy and when

Anti-aggregants (anti-platelets)
Patients who have had recent or recurrent TIA/stroke should be considered high risk; therefore, advice on stopping medication should be sought from the patient’s prescriber.

Table 7. Which anti-aggregants should be stopped pre-biopsy and when

5.4 DRE at pre-biopsy examination (diagnosis)

DRE pre-biopsy is recommended for several reasons. DRE allows the practitioner to assess the patient’s tolerance of rectal examination and the ultrasound probe.

Pre-prostate biopsy studies have also demonstrated that:

- in ~18% of cases, prostate cancer is detected by suspicious DRE alone, irrespective of PSA level. [92]
- abnormal DRE is associated with an increased risk of higher GS and is an indication for biopsy. [93]