Cancer and Prostatic Diseases (2003) 6,53–55 ß 2003 Nature Publishing Group All rights reserved 1365–7852/03 $25.00 www.nature.com/pcan Periprostatic local anesthesia eliminates pain of office-based transrectal prostate

JS Jones1*, JC Ulchaker1, D Nelson1, ED Kursh1, R Kitay1, S Angie1, M Horvat1, EA Klein1 & CD Zippe1 1Urological Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA

Up to 96% of patient who undergo report pain. We performed periprostatic local anesthesia injection in an effort to improve patient acceptance of prostate biopsy. Sixty patients were randomized to receive either local injection of lidocaine in the periprostatic nerves or no anesthetic. Lidocaine was injected through a 7-inch spinal needle placed through a transrectal ultrasound biopsy guide. Ten-core were immediately performed. Following biopsy, all patients gave a Visual Analog Scale (VAS) assessment of their pain experienced during biopsy. A majority of patients reported Visual Analog Scale (VAS) scores in the moderate (28.6%) or severe (28.6%) ranges unless local anesthesia was given. Only one of 27 patients (3.7%) receiving local anesthetic reported moderate pain, and none reported severe pain. Mean VAS pain scores were 1.4 in the anesthetic group and 4.5 in the control group (P< 0.0001). No difficulty was encountered from scarring in the five patients who underwent nerve spring radical retropubic following local anesthetic injection. Periprostatic injection of local anesthetic essentially eliminates pain from prostate biopsy. Nerve-sparing radical retropubic prostatectomy is not more difficult as a result. Prostate Cancer and Prostatic Diseases (2003) 6, 53–55. doi:10.1038/sj.pcan.4500630

Keywords: prostate biopsy; local anesthesia; ultrasound

Introduction Biostatistics and Epidemiology randomized 30 patients to receive either periprostatic lidocaine (group one) or no Although up to 96% of patients report some degree of anesthetic (group two). Blinded randomization envelopes pain1 when prostate biopsy is performed, the standard were opened immediately prior to biopsy. of care has been to ignore this as a necessary downside to Patients were placed in the left lateral decubitus position the procedure.2 Some recent publications have suggested and the ultrasound probe was inserted transrectally. If pain may be controlled by periprostatic administration of patients were randomized to group one, the probe was local anesthetic,3–5 but others have shown no benefit.6 turned to the saggital plane with the biopsy guide switched Based on these early reports, we assessed feasibility of on prior to placement. A 22 gauge, 7-inch spinal needle was pain control using periprostatic injection of lidocaine on a placed through the biopsy guide channel under ultrasound randomized basis. guidance into the area where the prostatic innervation enters the gland. This was identified by angling laterally until the notch between prostate and seminal vesicle was visualized. Materials and methods The needle was placed into this notch and 5 cm3 plain lidocaine were injected on each side. Successful placement Based on our preliminary observations that pain scores was confirmed by observing the injectate cause separation of were decreased at least by half, the Department of the and prostate from the rectal wall. Ultrasound examination and volume calculation were then performed in both groups per routine. Ten biopsies *Correspondence: JS Jones, Urological Institute, the Cleveland Clinic Foundation, Suite A-100, 9500 Euclid Ave, Cleveland, OH 44195, USA. were taken immediately using a spring-loaded biopsy 7 Email: [email protected] needle as described by Gore et al. Biopsies specifically Accepted 24 July 2002 included any visible abnormalities. Local anesthesia for prostate biopsy JS Jones et al 54 All patients were asked to report a validated linear visual analog scale (VAS) score, with 0 denoting no pain and 10 equaling the worst pain the patient had ever experienced. In order to minimize investigator bias, all VAS scores were obtained by the nurse after the physician left the room.

Results Mean VAS scores were over threefold higher in control patients than in those who received local anesthetic (1.4 vs 4.5; P < 0.0001). Due to the dramatic difference in the two groups, the study was closed prior to enrollment of the last five patients. Only one patient in group one reported a pain score (4) Figure 1 Correct needle placement is shown in the notch between seminal in the moderate range of 4 – 7. In contrast, the majority of vesicle and prostate laterally. patients in group two reported pain scores in the mode- rate or severe ranges (28.6% in each). There was no investigators inject these nerves in three or four different difference in VAS scores among patients in either group sites on each side,9 a single injection as these nerves when analyzed by individual surgeon. The results are approach the prostatic base on each side prior to branch- summarized in Table 1. ing should be sufficient based on the neuroanatomy. This Injection of local anesthetic was completed in less than has been confirmed by our findings, in which all but one 60 s in all patients. There was no additional time delay patient early in the series received complete pain relief. taken before proceeding to biopsy in any patient. The other source of pain during prostate biopsy is the Pain was the only complication in either group. All rectum, where the only pain sensory innervation is below patients were given 4 days ciprofloxacin 500 mg twice the dentate line. Before we began performing peripro- daily beginning the day before the biopsy. No infections static anesthesia, we believed the apex was more sensitive were observed. Most patients in both groups noted minor to pain than the rest of the gland as reported by Kaver.10 urinary, rectal and seminal (if sexually active) bleeding, We now believe the increased pain experienced with but none required treatment. apical biopsy is due to the inferior rectal nerve pain Prostate cancer was identified in nine group A patients fibers below the dentate line. If the patient can feel the and 10 group B patients. Radical prostatectomy was needle lightly touching rectal mucosa overlying the apex, performed in six patients from each group. A nervo- we move slightly cephalad prior to passing through the sparing procedure was performed in five patients injected rectal wall. The needle is then angled back towards the with lidocaine. No scarring or other evidence of damage apex for these two apical biopsies. This avoids rectal from the injection was observed. sensory pain fibers below the dentate line, and has been better tolerated in non-randomized observation of patients biopsied after completion of the study. Discussion We acknowledge the lack of placebo control. However, to limit bias, we avoided coaching patient responses by Up to 96% of patients that undergo prostate biopsy report telling patients only that they might ‘feel a stick’, whether pain, but until recently this was ignored as a necessary or not they were receiving an anesthetic. This was con- downside to the procedure. The most recent edition of sistent with the non-randomized approach we used prior Campbell’s Urology states that anesthetic is not needed.2 to beginning the study as the investigators developed the However, from the patient’s standpoint a very different technique. Surgeons left the room immediately after view emerges. Almost one in five patients in a recent biopsy and VAS scores were recorded as soon as possible study declared they would refuse re-biopsy without gen- by the nurse to minimize bias as well. eral anesthetic.8 This is consistent with our findings that All patients in the Urological Institute are routinely 29% of patients biopsied without anesthetic complained asked to give a VAS score on every patient visit — a policy of severe pain. instituted after review by the Joint Commission of Prostatic anesthesia is achieved by blocking the pro- Hospital Accreditation (JCAHO). This makes it unlikely static sensory branches of the neurovascular bundles, that patient responses were affected by the inquiry about which originate in the pelvic plexus. These branches exit their pain. the neurovascular bundles posterolaterally as they course Despite these measures, it is still feasible that the results between rectum and prostate (Figure 1). Although some were affected by the lack of blinding physician and patient.

Table 1

Group Minor or no pain (VAS 0 – 3) Moderate pain (VAS 4 – 7) Severe pain (VAS 7 – 10)

One (anesthetic) 26/27 (96.3%) 1/27 (3.7%) 0 (0%) Two (no anesthetic) 12/28 (42.9%) 8/28 (28.6%) 8/28 (28.6%)

Prostate Cancer and Prostatic Diseases Local anesthesia for prostate biopsy JS Jones et al 55 As pain is subjective, patients might perceive greater care on over 30 patients outside this study group and in no case being taken to assure their comfort. In addition, the sur- has nerve sparing been more difficult than usual. geons might have been gentler in the study group. How- The technique is easily mastered in one or two cases by ever, there was no difference in pain scores when controlling urologists experienced in transrectal ultrasound. Success for individual surgeon, indicating that if there was differ- is based on placement of anesthetic in the proper site. This ence in surgeon technique when using anesthetic, the same is most easily identified by the ‘Mount Everest’ sign, a difference was carried out among the five surgeons equally. hyperechoic (due to periprostatic fat) pyramidal notch This appears unlikely. It is even more unlikely that this between prostate and seminal vesicle seen laterally in the could result in a three-fold difference in VAS scores. saggital plane (Figure 2). When this site is injected, an Operator technique will surely affect pain perception ‘ultrasonic wheal’ is seen to separate the rectum away during any office-based procedure. Gentle probe placement from the prostate and seminal vesicles. This wheal has not through the anal sphincter minimizes patient anxiety, poten- made visualization more difficult. tially affecting pain experienced during the biopsy punctu- res. The number and vigor of biopsies will affect results. VAS scores of controls in the published literature range from 2.56 to 5.0.11 This variation could result from intra- Conclusion institutional differences in technique, study populations or in data collection. The specific question asked is a This study confirms that most patients complain of mod- variable difficult to quantify. It is unclear from published erate to severe pain with prostate biopsy unless local reports whether patients were asked about total pain anesthesia is given. Periprostatic injection of local experience, including probe insertion, or just pain from anesthesia prevents prostate biopsy pain when performed the biopsy puncture. Our patients were asked specifically as described. The technique is easily mastered and repro- about their total pain experience. Probe insertion discom- ducible. No difficulty has been encountered with nerve fort is not altered by this technique, so this will contribute sparing during radical prostatectomy in patients who to the pain experience of both patients and controls.12 have undergone the procedure. The additional time This could explain why the study of Wu et al6 found lower required is minimal and does not otherwise delay biopsy. VAS scores among controls, as they apparently asked patients to rate their pain only for the biopsy procedure alone. Study populations will also experience pain differ- ently, based on regional, age or socioeconomic factors. References Therefore, comparing pain scores between studies from 1 Zisman A, Leibovich D, Kleinmann J, Siegel YI, Lindner A. The different institutions is difficult. However, within the impact of prostate biopsy on patient well-being; A prospective same population as shown in our study, local anesthetic study of pain, anxiety, and crectile dysfunction. JUrol2001; 165: appears to offer substantial benefit during biopsy as 445 – 454. performed in our institution by five different physicians. 2 Brawer MK, Chetner. Ultrasonography of the prostate and biopsy. In: Walsh MP, Alan B. Retnik MDE. Darracott Vaughan Injection of local anesthetic into the area of the neuro- MD Jr (eds). Campbell’s Urology, 7th edn. WB Saunders: vascular bundles would appear to have the potential to Philadelphia, PA, 1998, p 2508. cause scarring. If so, nerve-sparing prostatectomy would 3 Nash P, Bruce J Indudhara R et al. Transrectal ultrasound guided be theoretically more difficult. However, we have specifi- prostatic nerve blockade eases systemic needle biopsy of the cally assessed the area of injection at the time of each prostate. J Urol 1996; 155: 607. operation. In no case thus far has scarring been observed. 4 Soloway MS, Obek C. Periprostatic local anesthesia before ultrasound guided prostate biopsy. J Urol 2000; 163(1): 172 – 173. In addition to the five patients in this study, we have 5 Leibovici D, Zisman A, Siegel Y, Sella A, Kleinmann J, Lindner A. performed nerve-sparing radical retropubic prostatectomy Local anesthesia for prostate biopsy by periprostatic lidocaine injection: A double-blind placebo controlled study. JUrol2002; 167: 563 – 565. 6 Wu CL, Carter HB, Naqibuddin M, Fleisher LA. Effect of local anesthetics on patient recovery after transrectal biopsy. Urology 2001; 57(5): 925 – 929. 7 Gore JL, Shariat SF, Miles BJ et al. Optimal combinations of systematic sextant and laterally directed biopsies for the detection of prostate cancer. JUrol2001; 165: 1554 – 1559. 8 Irani J, Fournier F, Bon D, Gremmo E, Dore B, Aubert J. Patient tolerance of transrectal ultrasound-guided biopsy of the prostate. Br J Urol 1997; 79:60– 610. 9 Vaidya A, Soloway MS. Periprostatic local anesthesia before ultrasound-guided prostate biopsy: An update of the Miami experience. Eur Urol 2001; 40: 135 – 138. 10 Kaver I, Mabjeesh NJ, Matzkin H. Randomized prospective study of periprostatic local anesthesia during transrectal ultrasound-guided biopsy. Urology 2002; 59: 405 – 408. 11 Alavi AS, Soloway MS, Lynne CM, Gheiler L. Local anesthesia for ultrasound guided prostate biopsy: A prospective randomized trial comparing two methods. J Urol 2001; 134 – 1345. 12 Naughton CK, Ornstein DK, Smith DS, Catalona WJ. Pain and mobility transrectal ultrasound guided prostate biopsy: A pro- Figure 2 The ‘Mount Everest’ sign identifies a hyperechoic peak corres- spective randomized trial of 6 versus 12 cores. J Urol 2000; 163(1): ponding to the area illustrated in Figure 1 (arrow). 168 – 171.

Prostate Cancer and Prostatic Diseases