Local Anesthesia for Prostate Biopsy
Local Anesthesia for Prostate Biopsy
Title: Local anesthesia for office biopsy of the prostate: effects on pain control, quality
 of life and surgical intervention.

 Introduction: Local anesthetic should be administered prior to transrectal needle biopsy of
 the prostate to control pain in the office setting. Various centers have injected anesthetic
 in different regions in and around the prostate prior to biopsy. Patient experience with each
 technique has varied. We would like to determine which procedure provides the best pain
 control. In addition, we would like to know if the anesthetic placement has any effect on
 urinary patterns, bowel habits, and sexual function. Furthermore, for those patients found to
 have cancer and elect surgical treatment, we plan to evaluate if the anesthetic had an impact
 on surgical dissection of their prostate.

 Methods: The investigators plan to identify those patients who require prostate biopsy for
 diagnosis. Each patient will be randomly assigned to a different anesthetic injection group.
 During the biopsy protocol, our nurse will monitor the patient?s pain level according to the
 visual analog score. The patient will complete a pre-biopsy questionnaire and two post-biopsy
 questionnaires administered at 1 and 4 weeks after biopsy. He will receive results of the
 prostate biopsy pathology report within 48 hours by calling his primary referral service.
RESEARCH PROPOSAL AND PROTOCOL

 TITLE Local anesthesia for prostate biopsy: Effects on pain control, quality of life, and
 surgical intervention.

 SPECIFIC AIMS Local anesthetic (1% lidocaine) should be administered prior to transrectal
 needle biopsy of the prostate to control pain in the office setting. In this study, we would
 determine which location of injection manages pain best by comparing the patient?s subjective
 pain response as depicted by the visual analog score. In addition, we will evaluate how the
 prostate biopsy and anesthetic techniques changed the patient?s quality of life and determine
 what impact was observed during surgical dissection.

 SIGNIFICANCE Transrectal ultrasound-guided needle biopsy of the prostate is the gold standard
 for diagnosing prostate cancer. We perform approximately 80 of these procedures per month in
 our office setting. This intervention often sparks anxiety in patients due to the pain that
 may be encountered. In fact, past patient surveys show that 50-90% of patients suffered
 significant pain during their prostate biopsy when local anesthesia was not used1. Since the
 year 2000, we have been injecting local anesthetic prior to the biopsy. This allows us to
 obtain an average of 10 to 12 samples from the gland. Overall, most patients are able to
 tolerate this procedure without significant morbidity.

 The cost of an office biopsy at our clinic is close to $1800, while those done under
 anesthesia in an operating room can be over $7000. Patients may need to undergo this biopsy
 in a monitored setting if it is done at the time of an additional procedure or if a
 saturation biopsy is planned, where up to 30 samples may be taken. Other patients are done
 under anesthesia if they adamantly refuse office biopsy due to their anxiety over pain
 associated with the procedure.

 Pain is a subjective response and varies between patients. Various methods of anesthesia have
 been employed to control pain in the office setting. Our traditional method has been to apply
 local anesthetic lubricant to the rectum. Following this, we use a 22 gauge spinal needle
 under ultrasound guidance to place 5cc of lidocaine into the junction of the base of the
 prostate and seminal vesicle on each side of the gland, and draw the medication distally
 toward the apex. Other groups have been injecting the anesthetic directly into the prostate
 gland on the right and left sides of midline. Still, other centers have focused on
 anesthetizing only the apex of the gland. There is no consensus as to which location provides
 the best pain relief for the patient. This knowledge would be critical as more men undergo
 this procedure to identify prostate cancer as early as possible. It is a procedure that
 should be done successfully in the office setting to allow patients early diagnosis, while
 helping to contain medical costs and avoid the operating room.

 In addition, it is unknown whether the location of anesthetic injection causes differences in
 quality of life after the procedure. Specifically, we would be focused on determining how
 this changed urinary patterns, bowel habits, and sexual function. Furthermore, regarding
 patients who are found to have cancer and would like surgical intervention, we plan a future
 study to see if anesthetic has any influence on ease of dissection during prostatectomy.

 PRELIMINARY STUDIES Transrectal ultrasound-guided needle biopsy of the prostate was first
 described in 19892. In the beginning, only hypoechoic areas and palpated nodules were
 targeted for biopsy. Later, elevated serum prostate specific antigen (PSA) became a common
 indication for biopsy. The sextant biopsy was done to sample the gland, but it became
 apparent that many cancers were being missed3. More biopsies were needed and now, some
 centers will perform more than twenty biopsies in an office setting for thorough
 investigations 4-6.

 The autonomic nerves from the caudal roots of S2 to S5 detect pain from the prostate biopsy.
 These nerves travel to the prostatic vascular pedicles located posterolaterally to the gland
 and innervate the prostate capsule and stroma. In 1996 Nash described a technique to ease the
 pain from the procedure7. His team used transrectal ultrasound to place 5cc of 1% lidocaine
 into the region of this prostatic neurovascular pedicle between the junction of the base of
 the prostate and seminal vesicle. This was done on the right and left sides of the prostate,
 significantly decreasing pain during the procedure. Modifications have been made where
 injection begins at this location but the anesthetic is also drawn distally toward the
 prostate apex to numb pain fibers along the entire breadth of the gland8. Most centers use
 this method to obtain an office biopsy and some even use this technique to perform saturation
 biopsy in an office setting5. Traditionally, we have also been performing this anesthetic
 method in our clinic.

 Yet, another study has looked at intraprostatic administration of 1% lidocaine to provide
 anesthesia9. In this analysis, 10cc of 1% lidocaine was infiltrated in 2 or 3 sites on the
 right and left sides of the gland, drawing the anesthetic from base towards the apex of the
 prostate. This method was compared to the traditional method described above. The
 intraprostatic method was found to be a better analgesic technique.

 However, even in this study, the apical biopsies continued to be the most uncomfortable. This
 location often proves to be the most painful site to obtain samples from. It is thought that
 this region of the prostate gland lies beneath the dentate line and therefore, more pain
 fibers exist there. Groups have anesthetized this region only and found significant success
 in pain control10.

 No study has ever compared these various methods to each other to determine how to best
 alleviate patient discomfort during office biopsy of the prostate. With more men undergoing
 prostate biopsy, either for the first time or on a repeat event, it would be critical have
 this knowledge for the best patient satisfaction. We still do not know if the anesthetic
 causes difference in quality of life. In addition, for those patients who are found to have
 cancer on their biopsy, we need to determine if the local anesthetic has any effect on pelvic
 dissection during prostatectomy.

 INVESTIGATIONAL DESIGN AND METHODS

 A. Patient Population and Recruitment

 Our study will not exclude patients based on age or race. Any male patient seen in our clinic
 with the following conditions that warrant and consent to transrectal needle biopsy of the
 prostate would be recruited for this study:

 1. Elevated serum PSA

 2. Hypoechoic nodule incidentally discovered on transrectal ultrasound for other purposes

 3. Abnormal digital rectal exam (DRE)

 The following exclusion criteria must be in place to prevent complications and interference
 with data interpretation:

 1. Patients taking narcotics on a routine basis

 2. Patients on Coumadin therapy

 3. Patients with ano-rectal disease

 4. Patients with history of prostatitis, pelvic pain, pelvic floor tension myalgia, or
 other pain syndromes

 5. Patients with active prostate abscess or urinary tract infection

 6. Patients with allergy to local anesthetic

 B. Potential Patient Risk

 The risks in this study are no greater than the risks incurred during a standard office
 biopsy of the prostate. Most patients undergoing biopsy since the year 2000 have received a
 transrectal injection of local anesthetic prior to prostate biopsy. However, complications
 associated with transrectal needle biopsy of the prostate do include the following:

 1. Urinary tract infection, and even urosepsis

 2. Erectile dysfunction that is usually short-lived, but may take weeks to recover

 3. Rectal bleeding, ranging from minor spotting to severe hematochezia warranting
 interventions by a colorectal surgeon

 4. Hematuria, ranging from spotting to severe requiring Foley catheter placement and
 bladder irrigation

 5. Hematospermia that although not harmful to the patient, may last up to 2 months

 6. Hypotension due to vaso-vagal responses

 These risks are part of the actual prostate biopsy. Our study to apply local anesthetic to
 various regions around the prostate do not increase these risks and do not add any new
 additional risks.

 C. Risk Prevention

 There are several ways to prevent complication from office biopsy of the prostate. These
 methods have been employed by our staff since beginning this procedure in our clinic. Risk is
 decreased by enforcing the following pre-procedural guidelines:

 1. Stop all aspirin-containing or non-steroidal anti-inflammatory (NSAID) agents 7 days
 prior to the biopsy.

 2. Begin a quinolone (or other appropriate antibiotic) the night prior to procedure and
 continue this prophylaxis for a total of 5 days.

 3. If the patient has a prosthetic joint or heart valve, administer appropriate SBE
 prophylaxis one hour before biopsy.

 4. Administer one Fleets enema rectally at least one hour before biopsy.

 The risks that the patients would be subjected to are no different than if they were not a
 part of this study. All prostate biopsies are associated with a small risk, but most patients
 do not suffer long term consequences. Our study is meant to determine how to provide the best
 pain relief possible while obtaining tissue diagnosis and identifying prostate cancer as
 early as possible.

 D. Budget

 Funding will be sought from the Department of Urology Research Committee. These funds will be
 used for nursing support and statistical analysis. We will need nursing assistance for
 recruitment and consenting, as well as assisting with having patients complete the pre-biopsy
 survey. This will require approximately 10 minutes of the nurse?s time, allocated among
 approximately 243 study patients. In addition, the nurses will assist with the post biopsy
 survey administration and collection. Statistical analysis will be completed by our urology
 research statisticians. The small grants project funding of $5000 should allow complete
 coverage of this project. No special equipment, medications, or supplies will need to be
 obtained. We will be using materials that are a standard part of our practice. The patient
 will have to pay for the fees of the office biopsy, anesthetic, and pathology, but there will
 not be any other costs to them.

 E. Justification of Subjects

 Our statisticians have reviewed the prior studies regarding this subject. A total of 81
 patients will be required in each study arm to achieve 80% power to detect a difference in
 means of 0.4 points on the visual analog scale. This assumes that the common standard
 deviation is 0.9 using a two-tailed t-test with a 0.050 significance level.

 F. Research Protocol

 All patients who qualify for the study will be recruited at the time of their initial
 consultation with a urologist in our department. They will be met by our research study nurse
 and consented in the exam room. Then, they will be asked to complete the pre-biopsy survey.
 The patients will also be given a packet at that time which includes the post-biopsy surveys
 to be done at 1 and 4 weeks after the procedure. (All questions on both surveys will have
 been derived from previously validated questionnaires.) After consenting, patients will be
 randomized to one of three groups to determine how to best administer anesthetic prior to
 prostate biopsy:

 Group 1: Injection between the base and seminal vesicle on the right and left sides of the
 gland, while drawing the needle distally to ensure numbing of the prostate apex Group 2:
 Intraprostatic injection into 2 sagittal planes, beginning at the base of the prostate and
 traversing distally toward the apex on the right and left sides of the prostate Group 3:
 Injection at the apex of the prostate only, between the prostate and rectal wall, on the
 right and left sides of the gland

 The patients will have appropriately refrained from any aspirin or NSAID medications for at
 least 10 days. They will have started their appropriate antibiotic the night prior to biopsy.
 A Fleets enema will have already been administered by self one hour before the appointment.
 Upon arrival, they will meet with our urology biopsy nurse who will review the study once
 more with the patient. He will then administer 20% benzocaine (Hurricane) jelly to the
 patients rectum and prepare the patient in the standard knee-chest prone position.

 We will use the standard B-K 7.5 mHz transrectal side-fire ultrasound probe for the imaging
 in this procedure. The study-coordinator physician will then administer the anesthetic (1%
 plain lidocaine) through a 22g spinal needle under transrectal ultrasound guidance to each
 group as described above:

 Group 1: Inject 6cc of anesthetic into the junction between the base and seminal vesicle,
 while drawing out toward apex of the prostate on the right side. This will be repeated on the
 opposite side of the gland for a total of 12cc of anesthetic. Ultrasound will be used to
 confirm the presence of the anesthetic under real-time imaging.

 Group 2: Inject 3cc of anesthetic into a sagittal plane, beginning at the base of the
 prostate, and drawing distally toward the prostate apex. This will be repeated in another
 sagittal plane on the right side of the gland. The same process will be done on the left side
 of the gland. A total of 12cc of anesthetic will be applied and confirmed by ultrasound
 guidance.

 Group 3: Inject 6 cc of anesthetic just lateral to the prostate apex between the gland and
 rectum using ultrasound guidance to confirm its position. The same procedure will be repeated
 on the other side of the gland. A total of 12cc of anesthetic will be applied. (See Figure 1
 for images) A timer will be set at this point for a total of 3 minutes. The biopsy physician
 will then enter the room and the coordinator will leave. This doctor will perform an
 ultrasound exam of the prostate to search for abnormalities and obtain a volume measurement
 to estimate gland size.

 Following this interval, a total of 12 biopsies will be obtained. If no ultrasound lesions
 were identified, 2 apical, 2 base, and 2 mid-gland biopsies will be performed on each side of
 the prostate. If any hypoechoic regions are noted this will be counted toward the total
 number of biopsies, not to exceed 12 samples per patient. At completion of the biopsy, the
 patient?s rectum will be examined digitally and the penile meatus will be inspected to rule
 out significant bleeding requiring further intervention.

 Pain analysis is the first focus of this study and thus, we will use the well-established
 standard visual analog scale to provide patients with an index to rate their pain (See Figure
 2). Subjects will have the visual analog scale in front of them. They will be asked to
 provide a number corresponding to their pain level when our biopsy nurse requests them to
 rate their pain. We will ask at the time points listed below:

 1. Time of transrectal ultrasound probe insertion.

 2. Time of anesthetic needle insertion.

 3. Time of biopsies.

 4. At completion of biopsy session, to obtain overall pain response

 Patients will then be placed in the left lateral decubitus position and vital signs will be
 reassessed before slowly allowing the patient to move away from the biopsy table. He will
 then be allowed to get dressed and recover. The patient will then be allowed to leave our
 Gonda 7 urology clinic. He will be sent out with a reminder to complete the questionnaires at
 1 and 4 weeks after biopsy. These questionnaires will be used to assess quality of life
 changes that may be brought on by the prostate biopsy. Two surveys will be used to determine
 how long the changes lasted.

 In addition, our long term study will look at how the prostate biopsy and anesthetic methods
 affect surgical removal of the prostate. We will identify those patients who end up having a
 biopsy positive for cancer. If they elect surgical management, we will review the surgeon?s
 operative report to identify any difficulties he or she encountered in their case. We would
 compare our three groups to understand if an anesthetic location is associated with any
 difficulty in the surgical cases as coded by the staff surgeon. It will also be critical to
 review operative times and estimated blood loss among the three groups.

 G. Anticipated Results

 Prostate cancer is a major concern for men in our modern times. They will have to undergo
 prostate biopsy for diagnosis. This procedure is a vital part of the diagnostic armamentarium
 in urology. It can be a painful procedure, but there are ways to improve tolerance. In this
 study, we plan to define which anesthetic method provides the best pain relief during an
 office biopsy of the prostate. In addition, we will see how the anesthetic impacts quality of
 life and surgical interventions for cancer. This information will improve clinical practice
 and patient satisfaction with the procedure.
Our study will not exclude patients based on age or race. Any male patient seen in our
 clinic with the following conditions that warrant and consent to transrectal needle biopsy
 of the prostate would be recruited for this study:

 1. Elevated serum PSA

 2. Hypoechoic nodule incidentally discovered on transrectal ultrasound for other purposes

 3. Abnormal digital rectal exam (DRE)

 The following exclusion criteria must be in place to prevent complications and interference
 with data interpretation:

 1. Patients taking narcotics on a routine basis

 2. Patients on Coumadin therapy

 3. Patients with ano-rectal disease

 4. Patients with history of prostatitis, pelvic pain, pelvic floor tension myalgia, or
 other pain syndromes

 5. Patients with active prostate abscess or urinary tract infection

 6. Patients with allergy to local anesthetic