**4. Periprocedural considerations**

Prostate biopsy is potentially dangerous and painful procedure. Preparation, informed consent with explanation of possible complications, administration of proper antibiotic prophylaxis, policy on anticoagulant and antiaggregation medications and pain management should be standardized and followed in every patient.

### **4.1 Enema and needle handling**

Although bowel preparation with enema or clear fluids are not necessary before biopsy (Zaytoun et al., 2011) or no statistically significant increase in complication rate was identified with change of regimen (Ruddick et al., 2011), some still claim less septic complications with enema use (Kanjanawongdeengam et al., 2009) or even with the way enema is properly administrated (Huang et al., 2006). In the light of modern approaches to bowel surgery, extensive enemas really look outdated, but it is obvious rectum should be empty before biopsy and suppository in the evening or morning before biopsy seems very reasonable and appropriate. The future with development of resistant bacteria may even bring back old classical methods (cleaning rectum with povidone iodine enema or simply povidone iodine suppository), but at present this is not standard.

Question of role of re-inserting "dirty" needle. Most of us use one needle for the whole procedure (all cores). Some (Kisner in Maribor, Slovenia) have insisted on using sterilized needle with every core, others studied cleaning needle with povidone iodine solution during procedure (Koc et al., 2010). No decrease in complications was shown with those techniques.

#### **4.2 Antibiotics**

Most common causative organism for infectious complications following trus prostate biopsy is E.coli. Antibiotic prophylaxis is necessary and guidelines from European and American urological societies have been issued and regulate this question, although different antibiotic regimens are used in practice. Guidelines are freely accessible on web from the issuing societies (EAU and AUA) and provide also extensive lists of literature, which will therefore not be reviewed again here.

EAU guidelines (www.uroweb.org, 2010 edition) recommend antimicrobial prophylaxis, but admit choice of regimens remains debatable. They list studies which suggest single doses for low-risk patients and remark, prolonged course should be considered for high-risk patients. Expected patogens are Enterobacteriaceae and possibly also anaerobes. Recommended antibiotics are fluoroquinolons, TMP+SMX and metronidazole with question mark (no evidence).

1. If no targeted approach is available and also there is lack of funds (for example for C-TRUS ANNA), transrectal saturation biopsy may be performed and probably it may be

3. Stereotactic biopsy (TargetScan or transperineal) is definitely better opinion compared to free-hand saturation biopsy. Stereotactic approach may also be suggested after diagnosis, regarding watchful waiting or minimally invasive therapies planning.

Prostate biopsy is potentially dangerous and painful procedure. Preparation, informed consent with explanation of possible complications, administration of proper antibiotic prophylaxis, policy on anticoagulant and antiaggregation medications and pain

Although bowel preparation with enema or clear fluids are not necessary before biopsy (Zaytoun et al., 2011) or no statistically significant increase in complication rate was identified with change of regimen (Ruddick et al., 2011), some still claim less septic complications with enema use (Kanjanawongdeengam et al., 2009) or even with the way enema is properly administrated (Huang et al., 2006). In the light of modern approaches to bowel surgery, extensive enemas really look outdated, but it is obvious rectum should be empty before biopsy and suppository in the evening or morning before biopsy seems very reasonable and appropriate. The future with development of resistant bacteria may even bring back old classical methods (cleaning rectum with povidone iodine enema or simply

Question of role of re-inserting "dirty" needle. Most of us use one needle for the whole procedure (all cores). Some (Kisner in Maribor, Slovenia) have insisted on using sterilized needle with every core, others studied cleaning needle with povidone iodine solution during procedure (Koc et al., 2010). No decrease in complications was shown with those

Most common causative organism for infectious complications following trus prostate biopsy is E.coli. Antibiotic prophylaxis is necessary and guidelines from European and American urological societies have been issued and regulate this question, although different antibiotic regimens are used in practice. Guidelines are freely accessible on web from the issuing societies (EAU and AUA) and provide also extensive lists of literature,

EAU guidelines (www.uroweb.org, 2010 edition) recommend antimicrobial prophylaxis, but admit choice of regimens remains debatable. They list studies which suggest single doses for low-risk patients and remark, prolonged course should be considered for high-risk patients. Expected patogens are Enterobacteriaceae and possibly also anaerobes. Recommended antibiotics are fluoroquinolons, TMP+SMX and metronidazole with question

useful to perform MRI or choline PET-CT to help identifying suspicious areas. 2. If equipment and local expertise allow, any of the targeted biopsy methods (for example

C-TRUS ANNA or others) should be used.

management should be standardized and followed in every patient.

povidone iodine suppository), but at present this is not standard.

which will therefore not be reviewed again here.

**4. Periprocedural considerations** 

**4.1 Enema and needle handling** 

techniques.

**4.2 Antibiotics** 

mark (no evidence).

AUA guidelines (www.auanet.org, 2008 edition, reviewed 2010) also confirm prophylaxis is indicated in all patients as randomized controlled trials have confirmed significantly lower rates of complications in antibiotic groups. They also claim single dose may be adequate.

A lot depends on local antibiotic resistance patterns. For example, if TMP+SMX regimen is not used even for non-complicated urinary tract infections in one area, one would not use it for prostate biopsy prophylaxis either. One can never predict for sure future development of antibiotic resistance. Therefore, constant vigilance is needed and monitoring rates of infectious complications is necessary. Special attention should focus on repeat biopsies and this setting may sometimes deserve different antibiotic scheme or previous culture and susceptibility analysis. Later may be performed in two ways – patients with catheters or other urinary tract insertions may be screened using urine culture (Bruyere et al., 2010), but all who need screening should have their stools sample cultured for resistant strains. Resistant strains do occur and may significantly contribute to complications (Liss et al., 2011). Due to high probability of E.coli resistance to quinolones in cases of patients returning to hospital after prostate biopsy with quinolone prophylaxis, it is wise to use another antibiotic before cultures are known (although it seems obvious, people do often get prescribed flouroquinolone again). If there is no or low risk for ESBL, cephalosporines (probably third generation) may be the best initial guess (Zaytoun et al., 2011).

Although single dose is claimed useful, in our and many other situations most patients can be considered not low risk regarding infectious risk classifications (more than 65 years of age, concomitant diseases, like diabetes and lower urinary tract symptoms, incomplete bladder emptying). Therefore typical scheme (as we use it and others, for example (Campos-Fernandes et al., 2009), uses ciprofloxacin 500 mg twice daily started before biopsy and continued for three days. It was shown to decrease rate of complications after biopsy (Schaeffer et al., 2007). As every single infectious complication, even most minor, requiring any health-service contact, even only consultation, is seen as a big problem and aim is to avoid any complication, there are many patients who probably benefit from short course and not single dose antibiotic and this may be further reason why urologists are reluctant in accepting single dose only approach.

Metronidazol is added in some centers routinely, but most do not use it at present. However, it might be useful for specific patients, with specific predisposing conditions and in combination with other antibiotics (for example cephalosporins, although subjective experience shows more complications with their use for this purpose), when flouroquinolone resistance or intolerance is present.

Instead of 1-2 hour prior to procedure fluoroquinolone orally, same use parenteral aminogylcoside (gentamicin or amikacin) or aminopenicilline with betalactamase inhibitor (co-amoxiclav) at the time of biopsy, which is followed by oral antibiotic (often fluoroquinolone, but also others) at home. This scheme is used in some centers and may be helpful when compliance with oral regimen prior to biopsy is questionable or for allergy and non-tolerance to quinolones or in areas with high resistance to quinolones (Kehinde et al., 2008). Combination of periprocedural oral dose of ciprofloxacine with iv dose of gentamicin may be method of choice for single dose regimens.

Additional important recent problem regarding fluoroquinolones was finding significantly different serum concentrations of active drug comparing different generic manufacturers (Kehinde et al., 2010). Apart from probable reason for higher complication rate, substandard antibiotics preparations also contribute to resistance development as longer courses are needed and as a consequence low concentrations of drug are present in the environment for longer time.

Future of Prostate Biopsy: Who Will Get It and How? 121

warfarin (Brewster et al., 2010). This is not advisable, except aspirin and low molecular weight haparin, all other similarly working medications should be stopped before biopsy. Regarding clopidogrel, explicit agreement and consent between patient, his cardiologist and

Immediate complications, like fainting, diaphoresis should be controlled by adequate local

Rate of complications increases with time. Most important and frequent seem infectious complications. Reasons for increasing rates of complications may be increasing numbers of

Long term complications of prostate biopsy would be development of pain syndromes or problems with erectile function, which was described recently (Klein et al., 2010). This reminds us that indefinitely repeating biopsies and increasing number of cores per biopsy may not be the best way forward. Selective, targeted approaches must be taken seriously, as

Inhibitors of 5-alpha reductase (5ARI), finasteride or dutasteride, may be used short term to decrease blood flow in the prostate before biopsy (as described at the end of section 3.4.4). Further, it is speculated their longer term use (6 months or more) may decrease proportion of benign prostate in a whole gland and in this way increase chances for prostate cancer detection on prostate biopsy. It may also reduce development of low grade cancer. One possible strategy for use of 5ARI inhibitors is prescription of drug after first or second negative biopsy and then regular follow up of PSA. PSA is expected to decrease. Trigger for repeat biopsy is any increase of PSA above nadir or if PSA value under 5ARI is above 40% of initial PSA value. Described approach was recently retrospectively evaluated in abstract form, using REDUCE data (Roobol et al., 2011). However, a proportion of prostate cancers do progress (for example on watchful waiting) without this fact reflecting in increase of PSA. Therefore a possibility of prostate cancer progression (in patients on 5ARI treatment or without) while PSA values would not increase is a serious concern and needs further

research. We should always be aware, none of our methods is 100% successful.

TRUS ANNA or MRI-guided or MRI-US picture fusion guided biopsy.

Future of prostate biopsy will be interesting, a lot of new ideas and technologies are competing at present and it remains open which will, in the end, dominate the market and

Although new targeted technologies, either ultrasound or magnetic resonance, may improve detection and sampling and reduce need for increasing number of cores and repeat biopsy sessions, none seem at present nearing 100% sensitivity or specificity. At present, approximately 50% positive biopsy rate is expected in repeat biopsy setting using either C-

As burden of biopsies may increase dramatically in the near future (as explained above - (Quon et al., 2011)) further increases in complexity and technological demands may not be able to satisfy mass biopsy needs. Prostate biopsy is not very demanding procedure, potential harms and problems for patients do exist, but are not nearly as large as for different forms of prostate cancer treatments. Therefore, such a breakthrough as happened

urologist may result in exception, but extreme caution is needed.

prostate biopsy is not without its consequences.

**6. Chemopreventive stategies** 

**7. Conclusion** 

our every-day practice.

pain control. It is also not advisable for patients to be completely fasted.

cores per procedure or increased antibiotic resistance (Nam et al., 2010).
