european urology 53 (2008)

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1 european urology 53 (2008) available at journal homepage: Prostate Cancer Topical Prilocaine-Lidocaine Cream Combined with Peripheral Nerve Block Improves Pain Control in Prostatic Biopsy: Results from a Prospective Randomized Trial Marco Raber *, Vincenzo Scattoni, Marco Roscigno, Federico Dehò, Alberto Briganti, Andrea Salonia, Andrea Gallina, Valerio Di Girolamo, Francesco Montorsi, Patrizio Rigatti Istituto Scientifico Ospedale San Raffaele, Università Vita Salute, Cattedra di Urologia, Milan, Italy Article info Article history: Accepted September 7, 2007 Published online ahead of print on September 18, 2007 Keywords: Anesthesia Prostate cancer Biopsy Abstract Objectives: To compare pain control results between periprostatic nerve block alone and combined with topical prilocaine-lidocaine cream as local anesthesia of prostate biopsy. Methods: Three hundred patients were randomized to receive PNB (group 1), topical anesthesia of the anal ring, anal canal, and anterior rectal wall combined with PNB (group 2) and placebo (group 3). Patients were asked to use scale of 0 10 to complete a visual analogue scale questionnaire about pain during probe insertion (VAS1), periprostatic infiltration (VAS2), and cores (VAS3). Results: Pain during probe insertion in group 2 was significantly less than in groups 1 and 3 (VAS1, 0.29 vs and 1.48; p < ). Pain during periprostatic infiltration was also reduced in group 2 compared with group 1 (VAS2, 1.06 vs. 2.39; p < ). Pain control was similar during biopsy in the PNB and combined groups (VAS3, 0.43 vs. 0.37; p = 0.77) and was superior to group 3 (VAS3, 3.02; p < ). In younger patients (cut off, median age 67 yr) these differences were still significant between groups 1 and 2 (VAS1, 1.95 vs.0.31; p < and VAS2, 2.97 vs. 1,15; p < ), but not in older patients (VAS1, 0.91 vs. 0.28; p = 0.06; VAS2, 1.52 vs. 0,92; p = 0.06). Vagal symptoms were registered in 36 (12%) patients in all groups. Sepsis occurred in one group 1 patient and in one group 2 patient. Rectal bleeding was observed in one group 2 patient. Conclusion: Combined prilocaine-lidocaine cream topically placed with PNB is superior to PNB alone and may be of maximum benefit for younger patients. # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Istituto Scientifico Ospedale San Raffaele, via Olgettina, 60, I Milan, Italy. Tel address: marco.raber@fastwebnet.it (M. Raber) /$ see back matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 968 european urology 53 (2008) Introduction Prostate biopsy is considered an invasive procedure that may be painful and require some form of anesthesia [1]. The pain may have two origins: the transrectal probe insertion and multiple punctures of the anterior rectal wall, periprostatic soft tissue, and prostate capsule. The best pain control during prostate biopsy is achieved by periprostatic infiltration of lidocaine, so this anesthetic technique may be considered a gold standard [2 11]. This anesthetic method acts by reducing pain when cores are taken, but it cannot influence the pain that may originate when the transrectal probe is inserted [12]. Moreover, the periprostatic injection of lidocaine that is given to anesthetize the neural bundle bilaterally may cause pain and makes the entire biopsy procedure more uncomfortable [13]. We therefore administered a preventive topical anesthesia before inserting the transrectal probe, combined with periprostatic infiltration, to achieve more complete pain control during the entire biopsy procedure. The choice of a lidocaine-prilocaine mixture as a topical anesthetic was based on our previous study, which demonstrates a pain control advantage versus placebo when the transrectal probe is inserted and the prostate capsule is punctured [14]. The efficacy of topical prilocaine-lidocaine cream was reported by other authors as well [15 18]. To test our hypothesis, we compared topical-periprostatic combined local anesthesia with periprostatic alone in a three-arm placebo-controlled trial. 2. Methods From January 2004 to October 2004, 300 consecutive patients with abnormally elevated prostate-specific antigen (PSA) values or suspicious digital rectal exam (DRE) results, or both, underwent transrectal ultrasound (TRUS)-guided needle biopsy of the prostate by a single operator (M.Ra.). Exclusion criteria included lidocaine allergy, hemorrhagic diathesis, anticoagulation therapy, prediagnostic pain, chronic pain syndrome, rectoanal pathology, and/or urge urinary symptoms. Approval for this study was obtained from the ethics committee at our hospital. Each patient signed an informed consent. Patients were randomized by computer software to receive periprostatic nerve block (PNB) (group 1, 100 patients), topical anesthesia combined with PNB (group 2, 100 patients), and placebo (group 3, 100 patients). We calculated that at least 51 patients would be required per group to be able to detect a 1-point difference in the visual analogue scale, assuming a mean of 1.6 and a standard deviation (SD) of 0.9 in the PNB group [2] with a power of 80% and a type I error of To compare the results from the three groups, we performed the whole procedure in a similar step-to-step Fig. 1 Transrectal probe tip. fashion. A preliminary DRE was done 20 min before transrectal probe insertion in all patients. In the PNB group, immediately after insertion of the ultrasound probe, periprostatic tissues were infiltrated by 5 ml of 2% lidocaine into the neurovascular bundle at the seminal vesicle base on each side with a 7-in., 22-G spinal needle. The first core was taken after roughly 3 min. In the combined group, topical anesthesia was made at the time of DRE. A 5-ml syringe without a needle was filled with anesthetic cream (EMLA 1, AstraZeneca Inc, Macclesfield, UK). The cream was applied around the anal ring before the tip of the syringe entered the anal canal, and was delivered into the anal canal and rectum. During the following DRE, cream was spread and massaged along the anal ring, anal canal, and anterior rectal wall. The following steps were similar to the PNB group. Patients in the placebo group received the same procedure, but EMLA was substituted with gentamicin cream, which has an identical appearance. TRUS was performed with a 6.5-MHz end-fire probe (Hitachi Medical Systems Co, Tokyo, Japan). In all procedures we used the same dual-plane transrectal probe. Characteristics of the probe tip is shown in Fig. 1. The insertion procedure may be divided into two steps as follows: (1) The sagittal plane of the tip probe is rotated 908 clockwise with reference to the sagittal plane of the patient (Fig. 2); thus, Fig. 2 The probe is rotated clockwise so that the angle between the patient s sagittal plane and probe sagittal plane is 908.

3 european urology 53 (2008) Fig. 3 As the probe tip points towards the anal ring, the curved tip axis coincides with the anal canal axis. Fig. 5 As the tip enters the rectum, the probe handle is rotated 908 counterclockwise so that the probe sagittal plane and patient sagittal plane are coincident. orientation of the ovoid-shaped tip probe cross-section coincides with the anal ring and anal sphincter morphology (Fig. 3). (2) As the tip is pointed at the anal ring, the probe handle is moved down; in this way the plane of both the curved tip and the anal canal lie in the same direction (Fig. 4). This insertion technique enables less traumatic insertion through the anal ring and anal canal owing to minimal stretching of the anal sphincter muscle fibres. As the tip passes through the anal canal and enters the rectum, the probe is rotated 908 counterclockwise, and the sagittal plane of both the patient and the probe take the same direction so that the biopsy procedure can start (Fig. 5). Prostate size was determined in the three groups according to standardized three-dimensional measurements computed by the ultrasound machine. Prophylaxis was carried out by the oral administration of ciprofloxacin 250 mg, one tablet every 12 h, starting the evening before sampling until 4 d after the procedure. A cleansing enema was self-administered on the morning of the biopsy. Biopsies were performed with the patient in the left lateral decubitus position; an 18-G Tru-cut needle powered by a biopsy gun (Manan Pro-Mag 2.2, Manan Medical Products, Northbrook, IL, USA) was used. In all cases, 14 core biopsy samples were taken. Three prostate cores were randomly obtained from each peripheral side, and two cores from the apical margin and base. In our practice, the biopsies are performed with the assistance of a nurse who is in charge of releasing the specimens from the biopsy gun and recharging it immediately after. Biopsy time was recorded in all cases. Topical anesthesia, periprostatic infiltration, and placebo were administered by the same operator (M.Ra). Immediately after the procedure, another operator (M.Ro.), who was blind to the treatment, asked the patients to complete a questionnaire about subjective pain; in particular, they were asked to use a scale of 0 (no pain) to 10 (maximal pain) to complete a visual analog scale questionnaire about pain during the transrectal probe insertion in all groups (VAS1), periprostatic infiltration in all but the placebo group (VAS2), and biopsy punctures in all groups (VAS3). Finally, complications during and after the procedure (48 h) were recorded. Vasovagal responses were rated as none, mild (diaphoresis with systolic blood pressure greater than 95 mm Hg), moderate (systolic blood pressure less than 95 mm Hg, requiring intravenous atropine as well as fluid administration), and severe (associated with neurological events such as seizure or loss of consciousness). We analyzed the ordinate 0 10 scales that were used to grade patient symptoms as continuous variables. We used the Student t test to evaluate these and other continuous variables; the chi-square test was applied for categorical data. 3. Results Fig. 4 The probe tip enters the anal canal and the probe handle progressively is moved up until the probe handle axis coincides with the anal canal axis. The mean age SD of the 300 men was (range, 35 89). The PNB group (group 1, 100 patients), combined anesthesia group (group 2, 100 patients),

4 970 european urology 53 (2008) Table 1 Patients characteristics Periprostatic group 1 Combined group 2 Control group 3 p value Mean age NS Mean prostate volume (ml) NS Mean PSA levels (ng/ml) NS No. of core biopsies Core sampling time (s) NS Abnormal DRE (%) NS Abnormal TRUS findings (%) NS Prostate cancer (%) NS NS, not significant; PSA, prostate-specific antigen; DRE, digital rectal examination; TRUS, transrectal ultrasound. Table 2 Pain level during the three phases of biopsy procedure in the three groups Periprostatic group 1 Combined group 2 Control group 3 p value G1 vs. G2 Mean pain level during probe introduction (VAS1) < Mean pain level during periprostatic infiltration (VAS2) < Mean pain during biopsy (VAS3) VAS, visual analogue scale [score for phases as listed]; G1, group 1; G2, group 2. and control group (group 3, 100 patients) were comparable for age, prostate volume, PSA levels, DRE and TRUS findings, histological results, and operating times (Table 1). The probe produced a significantly higher pain score in the placebo and PNB groups than in the combined group ( and vs ; p < 0.001). The perception of pain was significantly reduced during periprostatic infiltration in the combined group compared with the PNB group ( vs ; p < 0.001). On the contrary, pain control was similar during biopsy in the PNB and combined groups ( vs ; p = 0.77) and was superior to the placebo group (vs ; p < 0.001) (Table 2). A subanalysis of pain scores according to the patients age, taking into account a cut-off age of 67 yr (median age), showed a more significant difference in mean pain score during transrectal probe insertion and periprostatic infiltration between the combined groups 2 and 1 ( p < ) in younger patients. This difference was not demonstrated in older patients in the same groups ( p = 0.06) (Table 3). No general or local side effects associated with local anesthesia were observed. Vagal symptoms were observed in 36 (12%) patients in all groups: 28 (9.3%) were mild and 8 (2.7%) were moderate. No severe symptoms were observed in any group. No statistical difference regarding vagal symptoms was demonstrated between groups. Sepsis occurred in one group 1 patient and in one group 2 patient. They were hospitalized and treated with intravenous Table 3 Subanalysis of pain scores according to the patients age PNB Combined Placebo p value Younger patients Number NS Average age NS Mean pain level at transrectal probe insertion < Mean pain level at PNB puncture < Mean pain level during biopsy Older patients Number NS Average age NS Mean pain level at transrectal probe insertion Mean pain level at PNB puncture Mean of pain level during biopsy PNB, periprostatic nerve block; NS, not significant.

5 european urology 53 (2008) Table 4 Minor complications in all groups Minor complications Group 1 Group 2 Group 3 Fever up to C Acute urinary retention Persistent hematuria Hematospermia Dysuria Mild rectal bleeding antibiotics, and the condition was completely resolved after 5 d. Rectal bleeding was recorded in one group 2 patient, who was also hospitalized and treated with rectal tamponade with no sequelae. Minor complications are listed in Table 4. No statistical difference was demonstrated between groups. 4. Discussion It is intuitive that a potential painful procedure should require some form of anesthesia. In our opinion, even if a selected patient s category might not necessarily need anesthesia (eg, the aging population), we think that an abundance of evidence exists in the literature suggesting that anesthesia should always be used [1 12]. Moreover, the detection rate of prostate cancer at rebiopsy is not negligible (10 22%), so reducing discomfort is important to improve patients acceptance of eventual multiple biopsies [19]. Several studies since the first report by Nash et al [2] in 1996 reported that using PNB during transrectal prostate biopsies guarantees the best pain control. Most prospective, randomized, and placebo-controlled studies suggest that this anesthetic technique should be considered the gold standard [2 11]. In only one study by Wu et al [15], lidocaine injection lateral to the seminal vesicles before prostate biopsy showed no reduced biopsy-associated pain. This lack of pain control may mainly be explained by a too lateral injection site and too little lidocaine solution [5,7]. PNBs do not completely eliminate pain. In fact, pain that originates from inserting a transrectal probe may be even more painful than a biopsy [12]. Moreover, a transrectal lidocaine injection bilaterally to the prostate base may also be painful and cause discomfort [13]. Thus, another local anesthesia is needed in the first part of the biopsy procedure. Intrarectal lidocaine gel alone has shown conflicting results for pain control during biopsies [20 23] and during transrectal probe insertion [24,25]. Öbek et al [26] hypothesized that topical intrarectal lidocaine gel application combined with PNB was superior to PNB alone and concluded that this combined local anesthesia could be considered the new gold standard. They did not demonstrate statistical significance between biopsy pain scores. Moreover, they evaluated pain from the procedure as a whole and not pain specifically from the biopsy portion of the procedure. When we considered only the biopsy portion of the procedure, we found the same effective pain control in two groups (VAS3, 0.43 vs. 0.37, p = 0.77). However, in our opinion, the value of combined local anesthesia versus PNB alone is related to effective pain control in the first part of the biopsy procedure or when the transrectal probe is inserted, the anterior rectal wall is pierced by the PNB needle, and the periprostatic infiltration is made. In these terms, we clearly demonstrated the superiority of combined local anesthesia in controlling pain during all phases of the biopsy procedure ( p < ). We chose prilocaine-lidocaine cream because we showed its efficacy over placebo in a previous study [14]. The formulation of this synergistic mixture yields a higher concentration (approximately 80%) of active substance, compared with the commonly used lidocaine gel, which yields approximately 20% [27]. This property leads to a better penetration of the drug and better anesthetic effect. This procedure was demonstrated to be safe. The most frequent complication related to the biopsy was vagal symptoms. In one previous multicenter prospective study on biopsy morbidity on a large series of patients without local anesthesia, vagal symptoms were rated as mild, moderate, and severe [19]. These series showed a 2.8% incidence of moderately and severely symptomatic patients. According to this classification, we similarly found a low incidence of such symptoms in the placebo group (3%). Moreover, the rate of symptomatic patients in the PNB group is similar to the placebo group (3%); in the combined group, this value is lower (1%) but is not statistically significant, probably because the statistical sample was too small. With the support of these data, we can hypothesize that combined local anesthesia may reduce the impact of vagal symptoms. Less frequent complications were observed in two (0.6%) patients who developed postbiopsy sepsis, which agrees with data reported in the literature [28,29]. Procedure interruption because of unbearable pain is not common in our experience. In our data not yet published, we recorded 56 cases of such events in 3150 cases (1.8%). If we considered the unanesthetized group only, the incidence increased

6 972 european urology 53 (2008) up to 5.2%. In the present study, however, we did not record any procedure interruptions. Nowadays, the use of the control placebo group may seem not only useless, but even unethical. Our study was designed in 2003, when in our routine practice, we did not administer local anesthesia to every single patient. We believe that our design matches what is reported in studies performed in the same time period. Another concern on this topic might be that, to be a real placebo group, this group should have received a periprostatic injection of saline instead of local anesthetic. We did not administer a saline injection because we considered it to be an unethical, useless, and painful procedure. In the placebo group, we reported pain score levels lower than those of other studies under the same conditions. Indeed, reported pain scores by some authors were as high as 5 [16,18,30]. We do not have any explanation for these results. We can only hypothesize that a faster operating time played a role in pain level as well as the need of procedure interruption because of pain. Moreover, geometry, size, and introduction modality of the transrectal probe may result in a less painful procedure. The combined and PNB groups received DRE 20 min before the ultrasound probe insertion. Subsequently, the procedure proceeded similarly in the two groups. The PNB group in the present trial had a procedure that was not representative of how it is done in daily practice. This more complicated PNB procedure might affect the differences noticed. However, to compare the two anesthetic methods, we needed to take the same steps for both groups. Disadvantages of this anesthetic technique may be the costs related to prilocaine-lidocaine cream, leading to a charge of roughly 9 s per patient, and the relatively long timing of cream application before transrectal probe insertion. These disadvantages may be balanced by application in selected cases of younger or lower-pain-threshold patients. 5. Conclusion In our randomized double-blind placebo-controlled trial, we were able to demonstrate the superiority of combined prilocaine-lidocaine cream topically placed around the anal ring, anal canal, and rectal mucosa combined with PNB versus PNB alone. Whereas pain control during the biopsy procedure for the two anesthetic methods is similar, the preventive topical anesthesia was shown to be more effective in controlling pain when the transrectal probe was inserted and when the periprostatic infiltration was done. Combined local anesthesia may be of greatest benefit in younger patients, whereas, in older patients, it may be superfluous. Conflicts of interest The authors have nothing to disclose. References [1] Irani J, Fournier F, Bon D, et al. Patient tolerance of transrectal ultrasound-guided biopsy of the prostate. Br J Urol 1997;79: [2] Nash PA, Bruce JE, Indudhara R, et al. Transrectal ultrasound guided prostatic nerve blockade eases systematic needle biopsy of the prostate. J Urol 1996;155: [3] Soloway MS, Obek C. Periprostatic local anesthesia before ultrasound guided prostate biopsy. J Urol 2000;163: [4] Lynn NN, Collins GN, Brown SC, et al. Periprostatic nerve block gives better analgesia for prostatic biopsy. BJU Int 2002;90: [5] Rodriguez A, Kyriakou G, Leray E, et al. Prospective study comparing two methods of anaesthesia for prostate biopsies: apex periprostatic nerve block versus intrarectal lidocaine gel: review of the literature. Eur Urol 2003;44: [6] Leibovici D, Zisman A, Siegel YI, et al. Local anesthesia for prostate biopsy by periprostatic lidocaine injection: a double-blind placebo controlled study. J Urol 2002;167: [7] Berger AP, Frauscher F, Halpern EJ, et al. Periprostatic administration of local anesthesia during transrectal ultrasound-guided biopsy of the prostate: a randomized, double-blind, placebo-controlled study. Urology 2003;61: [8] Walker AE, Schelvan C, Rockall AG, et al. Does pericapsular lignocaine reduce pain during transrectal ultrasonography-guided biopsy of the prostate? BJU Int 2002;80: [9] Seymour H, Perry MJA, Lee-Elliot C, et al. Pain after transrectal ultrasonography-guided prostate biopsy: the advantages of periprostatic local anaesthesia. BJU Int 2001;88: [10] Kaver I, Mabjeesh NJ, Matzkin H. Randomized prospective study of periprostatic local anesthesia during transrectal ultrasound-guided prostate biopsy. Urology 2002;59: [11] Von Knobloch R, Weber J, Varga Z, et al. Bilateral fineneedle administered local anaesthetic nerve block for pain control during TRUS-guided multi-core prostate biopsy: a prospective randomised trial. Eur Urol 2002;41: [12] Luscombe CJ, Cooke PW. Pain during prostate biopsy. Lancet 2004;363: [13] Schostak M, Christoph F, Muller M, et al. Optimizing local anesthesia during 10-core biopsy of the prostate. Urology 2002;60:253 7.

7 european urology 53 (2008) [14] Raber M, Scattoni V, Roscigno M, et al. Perianal and intrarectal anesthesia before transrectal biopsy of the prostate: a prospective, randomized study assessing lidocaine-prilocaine cream versus placebo. BJU Int 2005;96: [15] Wu CL, Carter HB, Naqibuddin M, et al. Effect of local anesthetics on patient recovery after transrectal biopsy. Urology 2001;57: [16] De Maria M, Mogorovich A, Giannarini G, et al. Lidocaineprilocaine administration during transrectal ultrasoundguided prostatic biopsy: a randomized, single-blind, placebo-controlled trial. J Endourol 2006;20: [17] Galosi AB, Minardi D, Dell Atti L, et al. Tolerability of prostate transrectal biopsies using gel and local anesthetics: results of a randomized clinical trial. J Endourol 2005;19: [18] Adamakis I, Mitropoulos D, Haritopoulos K, et al. Pain during transrectal ultrasonography guided prostate biopsy: a randomized prospective trial comparing periprostatic infiltration with lidocaine with the intrarectal instillation of lidocaine-prilocain cream. World J Urol 2004;22: [19] Djavan B, Waldert M, Zlotta A, et al. Safety and morbidity of first and repeat transrectal ultrasound guided prostate needle biopsies: results of a prospective European prostate cancer detection study. J Urol 2001;166: [20] Desgrandchamps F, Meria P, Irani J, et al. The rectal administration of lidocaine gel and tolerance of transrectal ultrasonography guided biopsy of the prostate: a prospective randomized placebo-controlled study. BJU Int 1999;83: [21] Cevik I, Ozveri H, Dillioglugil O, Akdaş A. Lack of effect of intrarectal lidocaine for pain control during transrectal prostate biopsy: a randomized prospective study. Eur Urol 2002;42: [22] Chang SS, Alberts G, Wells N, et al. Intrarectal lidocaine during transrectal prostate biopsy: results of a prospective double-blind randomized trial. J Urol 2001;166: [23] Issa MM, Bux S, Chun T, et al. A randomized prospective trial of intrarectal lidocaine for pain control during transrectal prostate biopsy: the Emory University experience. J Urol 2000;164: [24] Matlaga BR, Lovato JF, Hall MC. Randomized prospective trial of a novel local anesthetic technique for extensive prostate biopsy. Urology 2003;61: [25] Stirling BN, Shockley KF, Carothers GG, et al. Comparison of local anesthesia techniques during transrectal ultrasound-guided biopsies. Urology 2002;60: [26] Öbek C, Özkan B, Tunc B, et al. Comparison of three different methods of anesthesia before transrectal prostate biopsy: a prospective randomized trial. J Urol 2004; 172: [27] Ehrenstrom Reiz GM, Reiz SL. EMLA a synergistic mixture of local anaesthetics for topical anaesthesia. Acta Anaesthesiol Scand 1982;26: [28] Rifkin MD. Biopsy techniques. In: Rifkin MD, editor. Ultrasound of the prostate. 2nd ed. Philadelphia: Lippincott- Raven; p [29] Lindert KA, Kabalin JN, Terris MK. Bacteremia and bacteriuria after transrectal ultrasound guided prostate biopsy. J Urol 2000;164: [30] Basar H, Basar MM, Ozcan S, et al. Local anesthesia in transrectal ultrasound-guided prostate biopsy: EMLA cream as a new alternative technique. Scand J Urol Nephrol 2005;39: Editorial Comment on: Topical Prilocaine- Lidocaine Cream Combined with Peripheral Nerve Block Improves Pain Control in Prostatic Biopsy: Results from a Prospective Randomized Trial Cesare Selli, Gianluca Giannarini Department of Urology, University of Pisa, Ospedale Santa Chiara, Pisa, Italy c.selli@med.unipi.it The authors are to be commended for the present study [1], which significantly adds to the existing literature on the timely and still controversial topic of analgesia during transrectal ultrasound (TRUS)-guided prostate biopsy (PB). It is now largely recognized that discomfort or pain during transrectal PB has a dual origin, arising from the insertion, permanence, and movements of the TRUS probe into the anal canal and rectum, and the needle punctures through the prostate capsule [2]. An increasing number of randomized controlled trials have proved the benefit of a combined form of analgesia, consisting of topically or systemically administered substances (ie, local anesthetics, muscle relaxants, or analgesics) and periprostatic nerve block (PPNB), over PPNB alone, which is currently considered the gold standard [3]. Consistent with these findings, the authors showed that PPNB combined with preliminary perianal and intrarectal administration of lidocaine-prilocaine cream compared to PPNB alone significantly reduced PB-related pain, by reducing discomfort caused by the TRUS probe and PPNB application. Pain of the sampling part was not lowered. These results seem to be convincing; nonetheless, we feel that some comments should be made. (1) A group of patients treated with topical lidocaine-prilocaine cream alone should have been included to make the trial more

8 974 european urology 53 (2008) appropriate, because topical cream might provide the same pain control as PPNB or combined anesthesia in selected patients. The rationale for including this group lies in the fact that, as demonstrated in previous studies [4], patients with a high anal discomfort threshold are likely to better tolerate the whole procedure, including the sampling part. In this respect, we observed similar results and proposed that patients with high anal compliance (arbitrarily defined as a score 2ona 10-point visual analogue scale [VAS] and assessed during preliminary, simple prostate TRUS), albeit a small part of the clinical spectrum, might not need analgesia at all, since pain evaluated after PB did not significantly increase [5]. (2) The assessment of pain at various stages of the procedure was performed retrospectively, thus possibly introducing a confounding factor. By doing it prospectively, the potential pitfall of patients recalling the most painful part of the procedure and giving a proportional (not absolute) value to the other ones ( recall bias ) would have been definitely overcome. (3) An additional possible selection bias may be advanced to explain the reason that VAS scores in the placebo group of the present series were remarkably lower compared to those reported in similar experiences [6]. In this respect, we are convinced that procedural time is not an issue because the learning curve for PB is limited and experienced urologists certainly equal the reported quickness, as long as the same template technique is adopted. We feel that future research should be focused on the real impact of TRUS probe geometry and size on the anal component of pain. This area has so far been neglected but represents the most heterogeneous material determinant in the whole PB procedure, preventing reliable comparisons. Additional studies exploring the efficacy of a combined analgesia technique in PB-related pain are needed before PPNB may be considered surpassed and a new gold standard is established. References [1] Raber M, Scattoni V, Roscigno M, et al. Topical prilocaine-lidocaine cream combined with peripheral nerve block improves pain control in prostatic biopsy: results from a prospective randomized trial. Eur Urol 2008;53: [2] Luscombe CJ, Cooke PW. Pain during prostate biopsy. Lancet 2004;363: [3] Scattoni V, Zlotta A, Montironi R, Schulman C, Rigatti P, Montorsi F. Extended and saturation biopsy in the diagnosis and characterization of prostate cancer: a critical analysis of the literature. Eur Urol 2007;52: [4] Philip J, McCabe JE, Roy SD, Samsudin A, Campbell IM, Javle P. Site of local anaesthesia in transrectal ultrasonography-guided 12-core prostate biopsy: does it make a difference? BJU Int 2006;97: [5] De Maria M, Mogorovich A, Giannarini G, Manassero F, Selli C. Lidocaine-prilocaine administration during transrectal ultrasound-guided prostatic biopsy: a randomized, single-blind, placebo-controlled trial. J Endourol 2006;20: [6] De Maria M, Mogorovich A, Giannarini G, Selli C. Perianal and intrarectal anaesthesia for transrectal biopsy of the prostate: a prospective randomized study comparing lidocaine-prilocaine cream and placebo. BJU Int 2006; 97: DOI: /j.eururo DOI of original article: /j.eururo Editorial Comment on: Topical Prilocaine-Lidocaine Cream Combined with Peripheral Nerve Block Improves Pain Control in Prostatic Biopsy: Results from a Prospective Randomized Trial Rolf von Knobloch Department of Urology, Franziskus Hospital Bielefeld, D Bielefeld, Germany rolf.von-knobloch@franziskus.de In their paper, Raber et al demonstrate the benefit of incorporating perianal together with intrarectal prilocaine-lidocaine cream in addition to standard periprostatic nerve block (PNB) for pain reduction during 14-core transrectal prostate biopsy [1]. Adding topical anaesthetic cream diminishes pain and discomfort caused by the insertion of the sonography probe and application of the PNB. Nevertheless, pain from the biopsy procedure itself is not reduced. Currently, urologists in academic centres commonly accept PNB during transrectal prostate biopsy to be the gold standard for pain control during the procedure [2]. Six years ago, when the first published prospective trials demonstrated the

9 european urology 53 (2008) efficacy of PNB for pain control during the biopsy procedure most urologists were reluctant to accept this additional effort mainly because they were convinced the biopsy procedure was well tolerated by their patients and often caused no pain [3 5]. This may be true for some patients but certainly not for the vast majority. The urologist as the investigator has no possibility in advance of identifying patients who will experience pain and, therefore, we have to offer all our patients an effective means of pain control. Neglecting an effective measure of pain control during an invasive diagnostic procedure would be highly unethical! Moreover, eliminating discomfort of a highly disturbing procedure in urologic outpatient practice results in higher patient satisfaction. Obviously, higher patient satisfaction can lead to a higher referral rate. After we introduced our PNB method during prostate biopsy in a large German town, we had a > 2.5-fold rise in prostate biopsy procedures performed annually within 18 mo (now > 500/yr) [5]. Although, we have to make every possible effort to reduce pain and discomfort during urologic examinations, adhering to the results of the above study would also mean applying an anaesthetic cream before every insertion of an ultrasound probe into the rectum and not just during the biopsy procedure. Whether this will become feasible in daily practice remains an issue of further debate. The results obtained by Raber et al have a pitfall, however. They are not generally applicable! The ultrasound probe used, with its characteristic geometry, causes discomfort during insertion into the rectum. Most probes have a much smoother shape and therefore barely cause more discomfort than an examining finger. Nevertheless, anaesthetic cream application before ultrasound-guided transrectal biopsy further reduces the pain of the procedure and should be incorporated whenever possible. References [1] Raber M, Scatton V, Roscigno M, et al. Topical prilocainelidocaine cream combined with peripheral nerve block improves pain control in prostatic biopsy: results from a prospective randomized trial. Eur Urol 2008;53: [2] Nash PA, Bruce JE, Indudhara R, et al. Transrectal ultrasound guided prostatic nerve blockade eases systematic needle biopsy of the prostate. J Urol 1996;155: [3] Alavi AS, Soloway MS, Vaidya A, et al. Local anesthesia for ultrasound guided prostate biopsy: a prospective randomized trial comparing 2 methods. J Urol 2001;166: [4] Schostak M, Christoph F, Müller M, et al. Optimizing local anesthesia during 10-core biopsy of the prostate. Urology 2002;60: [5] von Knobloch R, Weber J, Varga Z, et al. Bilateral fineneedle administered local anaesthetic nerve block for pain control during TRUS-guided multi-core prostate biopsy: a prospective randomised trial. Eur Urol 2002; 41: DOI: /j.eururo DOI of original article: /j.eururo