Prior to the prostatic biopsy, a urine culture should always be performed to exclude urinary infection. The recommended pre-procedural antibiotic prophylaxis continues to be second-generation fluoroquinolones, such as Ciprofloxacin (500 mg) which is more effective than ofloxacin (400 mg) [18]. The tablets are best taken 1–2 h before the procedure. Ceftriaxone is an alternative in cases of allergy to fluoroquinolones. There are reports of ciprofloxacin-resistant Escherichia coli in the faecal flora [19, 20] which may justify the combination with other antibiotics in some cases, e.g. ertapenem and amikacin [21–23].

Here again the patient’s positioning varies according to teaching institutions, from the lithotomy position (doctor sitting between the legs like for a cystoscopy) to the left lateral position with flexed hips and knees (doctor sitting behind the patient). The former is the preferred position for high-risk patients undergoing the procedure under sedation and close monitoring in operating theatres.

TRUS-guided prostatic biopsy performed under local anaesthesia through a periprostatic infiltration has been proven superior to instillation of intrarectal anaesthetic creams such as 1 % lidocaine solution (Xylocaine® or lignocaine) [24]. Low-dose aspirin is no longer considered an absolute contraindication for prostatic biopsy [8, 25]. Large studies have also suggested that discontinuation of warfarin is not necessary [26, 27] as long as the international normalized ratio (INR) is within the therapeutic range. However, if a history of coagulopathy is discovered, the patient should have his coagulation profile normalized prior to the prostatic biopsy. The recommended points of technique on performing the first biopsy are [28]:

Complications: A retrospective review of nearly 6,000 TRUS-guided biopsies of the prostate performed over 10 years has revealed the following complications [29]:

Interestingly this study did not show increased morbidity when comparing three different protocols with 6, 10 and 15 core biopsies. Vasovagal reaction is also known to occur.

In a recent study the mortality rate within 120 days after prostate biopsy (0.1%) was not found to be higher than in a control group (0.18%), and the deaths were mainly associated with risk factors such as ischemic heart and respiratory diseases [30].

The transperineal prostate biopsy is an alternative to the transrectal route when the anal orifice is closed after previous rectal surgery. It is also a valuable approach for patients with initially negative TRUS-guided biopsies and persistently high PSA or MRI images showing suspicious anteriorly located lesions [31].

The primary histopathological diagnosis of PC should ideally be confirmed by two pathologists. After staining the prostate cores with haematoxylin and eosin (H&E stain), the pathologists will first study the architectural patterns (presence of small glands with haphazard distribution, cribriform, fused and poorly formed glands or solid sheets, cords or isolated cells), the nuclear atypia (increase nucleocytoplasmic ratio with prominent nucleoli) and the prognostic factors like invasive growth and presence of perineural infiltration [32] (Fig. 3.3a–c). Additional immunohistochemical studies are sometimes needed for small tumour foci to identify invasive adenocarcinoma which is characterized by a loss of basal cells and, consequently, negative basal cell markers (34βE12 and p63). Conversely there will be a positive study for alpha-methylacyl-CoA racemase (AMACR, also called 504 s) which is upregulated in prostate carcinoma [32] (Fig. 3.4). Nonetheless immunohistochemistry should be reserved only for equivocal cases where conventional pathology is inconclusive [33]. PC histopathological grading was first reported by Gleason [34] and was modified later by the International Society of Urological Pathologists (ISUP) [35] (Table 3.1). The histopathological report must also include the localization and the number of positive cores out of the total number (generally 12), as well as the length of the malignant tissue in millimetres in every positive core. This is reported as a percentage of the total length of the positive cores. Several studies have demonstrated that the total tumour length in biopsy cores is an important prognostic factor. This was even suggested to have a stronger correlation with overall survival than the patient’s age, serum PSA or Gleason score [36]. This factor is taken into account especially when considering a patient for active surveillance (see later).

A repeat biopsy is indicated within 3–6 months in the presence of atypical small acinar proliferation (ASAP) as this is associated with a subsequent PC diagnosis in 40 % of patients [37]. It is also performed when extensive prostatic intraepithelial neoplasia (PIN) is seen on multiple sites (≥2 cores) carrying a 20–30 % risk of cancer [38, 39], as well as when the PSA is rising with the appearance of a prostate nodule during regular follow-up. However non-extensive (unifocal) high-grade PIN as an isolated finding is no longer considered an indication for repeat biopsy [40] unless there are new changes suggesting disease progression, i.e. PSA increase or appearance of a nodule on DRE during subsequent follow-up. Here it is recommended to perform MRI in order to define the suspected zone. If MRI is not available, 4–6 biopsies should be taken at the apex and the transitional zone in addition to the standard 12 biopsies [41]. A saturation biopsy exceeding 20 cores can also be recommended in highly suspicious cases with a previous negative biopsy. The incidence of PC detected in such circumstances is reported to be between 30 and 43 % [42].