If radical treatment is considered, biopsies should only be performed if the patient meets the inclusion criteria for age and comorbidity. If these criteria are met, biopsies should be performed in a standardized manner where all regions of the prostate are biopsied, usually by means of 10–12 cores [6].

If focal treatment is considered, prostate biopsies have a double role, to rule in prostate cancer in the part of the prostate that will be treated and to rule out prostate cancer from the regions of the gland that is not going to be treated. Ruling out prostate cancer usually requires more biopsies than when the objective is to rule in before treatment. Ruling out biopsies is often done in a second procedure within few months of the primary biopsies. In such cases, a different antibiotic prophylaxis should be considered [12, 13].

If radical treatment is postponed for a patient with low-grade prostate cancer, the patient will most likely come back for repeat biopsies to monitor the progress of the tumor. The increased risk of infective complications for repeat biopsies should be discussed with the patient before including him in a surveillance protocol.

Sometimes patients present with clear evidence of metastatic or locally advanced prostate cancer such as elevated PSA, metastases on imaging, and characteristic findings on DRE. Often these patients are older, have a catheter and a preexisting bacteriuria, and thus are at increased risk of infection after prostate biopsies. In such patients, starting reversible hormone treatment without histological confirmation of diagnosis may be justified.

Before the era of PSA, men with prostate cancer presented with voiding problems and underwent transurethral resection with minimal risks of side effects. Diagnosis was based on histological examination of TURP (transurethral resection of the prostate) specimens. When patients came to discuss prostate cancer treatment, their voiding problems were solved and their potency was preserved.

Today patients present with elevated PSA, usually in the absence of voiding problems, to discuss if a biopsy shall be taken. Already at that time point we have to discuss if they are willing to sacrifice their potency and continence in the event that a biopsy reveals prostate cancer and radical prostatectomy is recommended.

The transrectal approach is the most commonly used. The biopsies are either taken through a side-fire channel at an angle of 22° to the probe, or through an end-fire channel parallel to the probe. Using a side-fire probe, the biopsies are mainly taken from the posterior part of the prostate, and sampling the apical region is difficult. An end-fire probe enables easier sampling of the anterior part and the apical region.

In both methods, the biopsy needle traverses the same channel in the probe and passes through the rectal wall each time a core is taken. Usually, the same biopsy needle is used for all cores.

Perineal biopsies are also taken by way of a transrectal ultrasound probe, but the needle is steered through the holes in a metal template which is mounted on a stepper and also carries the ultrasound probe (Fig. 9.1). Transperineal biopsies are technically demanding because the needle has to travel a longer distance and may more easily change its course inside the prostate. However, the skin can be disinfected and the needle does not have to pierce the rectal wall so the procedure is less contaminated than the transrectal approach.

New equipment is available which makes use of a single channel through the skin and the pelvic floor for all biopsies. Due to the reduced contamination, the risk of infective complications is also lower [14]. However, transperineal biopsies require sedation or general anesthesia, the setup is more resource demanding and other side effects may be significant [15].

The most commonly used method of guidance is transrectal ultrasound. In patients that have been operated with amputation of the rectum, transperineal biopsies may be guided by a transabdominal probe. In conventional ultrasound-guided biopsies, the needle is usually removed immediately after a core has been taken.

With image-fusion systems and MRI-guided biopsies, the needle must remain inside the prostate while its position is being tracked either by scanning with 3D ultrasound or while new MR images are taken. Furthermore, image-fusion biopsies are more commonly used when anterior tumors are suspected. This means that the tip of the biopsy needle often travels all the way through the prostate and into the veins on the anterior surface of the gland. Image-fusion-guided biopsies are also often repeat biopsies. These factors may increase the risk of infective complications.

A meta-analysis of DRE estimated its sensitivity for detecting prostate cancer to be 59 % and its specificity 94 % [17]. This means that DRE cannot be used to rule out prostate cancer in a patient with elevated PSA.

Most patients are referred to prostate biopsy because of elevated PSA on repeat examinations after excluding urinary tract infections and prostatitis. The sensitivity of PSA as judged by classical screening biopsies and a PSA cutoff of 4.0 ng/mL was 21 % for detecting any prostate cancer. This means that 79 % of tests are falsely negative, a fact that explains why patients with a persistently elevated PSA keep coming back for repeat biopsies [18]. The low sensitivity of PSA is a strong argument for better biomarkers. Long noncoding (lnc) RNAs like PCA3, ANRIL/P15AS, PCAT1, PCGM1, PTENP1, SChLAP1, and SPKY4-IT1 are appearing as the next generation of biomarkers expected to significantly improve early diagnosis, risk stratification, treatment monitoring, and even targeted treatment [19].

During the last decade, we have witnessed rapid developments in the use of MRI for diagnosis and staging of prostate cancer. Initially, MRI findings were used as a targeting aid for cognitively guided TRUS (transrectal ultrasound guided) biopsies. This technique has now been replaced by image-fusion systems which enable the replacement of random biopsies with a few targeted biopsies and precise recording of biopsy sites (Fig. 9.2). MRI has improved T-staging and the planning of radical treatment.

In the recent few years, MRI has also been introduced to rule out prostate cancer. Although the negative predictive value of MRI in elite centers is high, there is not yet enough data to support the widespread use of MRI as a screening tool [6].

While MRI may not do away with the need for prostate biopsies altogether, it may reduce the number of cores taken per biopsy procedure by facilitating targeted prostate biopsies and reduce the need for repeat biopsies. Unfortunately, there is still no evidence that this will reduce the number of infective complications, but this is definitely an important research question. Before we can study this, we need better knowledge about the negative predictive value of MRI.

Comparative studies are not available, but we know from observational studies that the risk of infective complications after repeat biopsies is approximately 15 % [4, 5]. Therefore, any measure that will reduce the need for repeat biopsies is important. Today patients who are coming in for repeat biopsies either have a rising PSA and negative screening biopsies or are in a surveillance program. It is expected that early MRI followed by targeted biopsies may reduce the need for repeat biopsies, particularly for patients who are shown to have anterior tumors. With better negative predictive value, MRI is also expected to reduce the need for repeat biopsies in surveillance programs.

The sequence of screening steps remains analysis of PSA followed by random biopsies. The best way to avoid infective complications is to avoid repeat biopsies. Better biomarkers and imaging techniques with better negative predictive values are important research areas.

The most important specific risk factor for the development of infective complications after prostate biopsy is antibiotic treatment or prophylaxis within the last few months [20]. Other risk factors that increase the chance of a contaminated environment are an indwelling catheter, a history of urinary tract infection or prostatitis, and travel to regions with a high prevalence of antibiotic resistance. Also important are comorbidities that reduce the immunocompetence of the patient such as diabetes, smoking, and a range of immunocompromising treatments. Disturbances in coagulation, for example, use of anticoagulants, are important for the risk of bleeding.

The ESIU/EAU (European Section for Infections in Urology/European Association of Urology) recently introduced the concept of phenotyping to better describe the different groups of risk factors for urogenital infections, the so-called ORENUC system (Table 9.2) [21]. The system has six main categories. Each category is referred to by a letter and all letters together give the name ORENUC. A history of UTI during the recent 6 months or asymptomatic bacteriuria are important category U risk factors, while having an indwelling catheter is a category C risk factor.

A careful history prior to prostate biopsy helps the clinician to tailor the prophylaxis to the patient and to identify risk factors that must be considered or eliminated in order to avoid complications.

The fact that some patients do not have rectum must not be overlooked. Before a patient is scheduled for prostate biopsy, it must be checked that a digital rectal examination (DRE) has been performed and that the anus is passable for a sonotrode. A urine culture should be taken if there is a history of urinary tract infection or prostatitis. Otherwise, a urine dipstick test is adequate. A rectal swab is recommended if there is a risk for fluoroquinolone-resistant or ESBL-producing bacteria.

The need for a thorough discussion about the indication for biopsy, the work-up necessary based on the clinical history, a clinical examination, and the performance of screening tests are arguments for not carrying out biopsies at the first visit. This also enables the patient to give fully informed consent for the biopsy procedure.