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Oncology

rostate Brachytherapy After Ilealouch–Anal Anastomosis Reconstruction

ichard Williamson, Marc C. Smaldone, Erin P. Gibbons, Ryan P. Smith, Sushil Beriwal,nd Ronald M. Benoit

BJECTIVE To determine the safety of prostate brachytherapy in patients with clinically localized prostatecancer who have undergone proctocolectomy with ileal pouch–anal anastomosis (IPAA).

ETHODS We performed a retrospective chart review of patients with a prior history of IPAA reconstruc-tion who underwent prostate brachytherapy at our institution. Clinical records were reviewed fordemographic characteristics, postoperative dosimetry, changes in bowel function, and oncologicoutcomes. Data were analyzed using descriptive statistics.

ESULTS Five patients with an IPAA underwent prostate brachytherapy for clinically localized prostatecancer. Mean time from colorectal reconstruction to prostate brachytherapy was 6.3 years.Adequate dosimetry (mean D90 114.9%, mean V100 91.1%, mean R100 0.76 mL) was achievedin each patient. Bowel frequency worsened in the immediate postoperative period in all patients,but all patients returned to their baseline bowel pattern by 4 months after their procedure.Serious complications, such as J-pouch ulcers, fistulas, or fecal incontinence, did not occur inthese patients.

ONCLUSIONS Prostate brachytherapy is a safe treatment option in patients with clinically localized prostate cancerand a history of proctocolectomy and IPAA reconstruction. UROLOGY 73: 369–373, 2009. © 2009

Elsevier Inc.

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atients diagnosed with clinically localized prostatecancer have several options for treatment of theirdisease, including radical prostatectomy, external

eam radiotherapy, and prostate brachytherapy. Patientsill decide which treatment option best suits their needsn the basis of the stage and grade of their disease, theirisk tolerance for potential complications such as urinaryncontinence and erectile dysfunction, and the degree ofnvasiveness of treatment. However, in select patients,pecial circumstances can limit these treatment options.ne such situation arises in men who have undergone

roctocolectomy and construction of an ileal pouch-analnastomosis (IPAA).

The management of clinically localized prostate cancern patients with a history of prior proctocolectomy andPAA is challenging. These patients are poor candidatesor radical prostatectomy owing to loss of anatomic tissuelanes, denervation of pelvic musculature, and pelvicdhesions.1 External beam radiotherapy is contraindi-ated owing to concerns over pouch toxicity.2 Prostaterachytherapy may be an attractive modality in this

rom the Department of Urology, University of Pittsburgh, School of Medicine,ittsburgh, Pennsylvania; and the Department of Radiation Oncology, University ofittsburgh, Medical Center, Cancer Center, Pittsburgh, PennsylvaniaReprint requests: Marc C. Smaldone, M.D., Department of Urology, University of

ittsburgh, School of Medicine, Suite 700, 3471 Fifth Ave, Pittsburgh, PA 15213.

t-mail: smaldonemc@upmc.eduSubmitted: April 28, 2008, accepted (with revisions): June 28, 2008

2009 Elsevier Inc.ll Rights Reserved

atient population because of the potential sparing ofadiation to the pouch. The present series reviews ourxperience performing prostate brachytherapy in patientsfter proctocolectomy and IPAA reconstruction.

ATERIAL AND METHODS

sing a protocol approved by the institutional review board atur institution, the medical records of all patients who under-ent prostate brachytherapy at our institution between 2001nd 2007 were reviewed. Five patients were identified with aistory of previous proctocolectomy and IPAA. All patients inhis cohort underwent proctocolectomy for ulcerative colitis.nformation obtained from the medical record included demo-raphic data, pretreatment prostate-specific antigen (PSA)alue, Gleason score, clinical stage, prostate volume, isotopesed, prescribed dose, postimplant dosimetry (D90 [dose to 90%f the prostate], V100 [prostate volume receiving 100% of therescribed dose], and R100 (volume of ileal pouch in milliliterseceiving 100% of prescribed dose]), bowel symptoms, andosttreatment PSA values.Prostate brachytherapy is performed at our institution using a

eal-time interactive technique with modified peripheral load-ng. The number and strength of seeds were ordered accordingo the preoperative transrectal ultrasound. Prostate volume wasbtained using the elliptical approximation (height � width �ength � �/6). No patients in this study were treated withupplemental external beam radiation. Three patients in ourohort were administered androgen deprivation therapy before

heir implantation. Two patients were administered androgen

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eprivation therapy before referral to our center, and 1 patientas advised to undergo androgen deprivation therapy given theresence of high-grade (Gleason 4�4�8) disease and our con-ern about adding external beam radiation in the face of anPAA. Patients were administered general anesthesia andlaced in the dorsal lithotomy position. A 7.5-MHz biplanarltrasound probe was then placed into the pouch and posi-ioned on the prostate. Despite the presence of a J-pouch ratherhan a rectum, no special maneuvers or procedures were nec-ssary to decrease the amount of radiation to the bowel. Aeripheral ring of needles was then placed, beginning anteriorlynd proceeding laterally and inferiorly. Central needles werelaced before placing the posterior needles. Care was taken tolace the central needles at least 5 mm from the urethravisualized on ultrasound by the injection of aerated gel lubri-ation into the urethra) and to place the posterior needles ainimum of 5 mm from the anterior pouch wall. All needlesere viewed in both the transverse and sagittal planes. Tech-ical adjustments were not required owing to the presence ofhe J-pouch.

Determination of seed number and location was performed inhe operating room on the basis of an institution-developedomogram that takes into account the prostate volume, actualeedle location, prescribed dose, and seed activity. Seeds werelaced with a Mick applicator (Mick Radionuclear Instruments,ronx, NY) with intraoperative adjustments made with the goalf obtaining a uniform dose distribution throughout the pros-ate with central sparing of the urethra. The prescribed dose was45 Gy in patients undergoing 125I implantation and 115 Gy inatients undergoing 131Cs implantation.Postimplant dosimetry was based on a postoperative com-

uted tomography scan after the implant. Axial slices at.25-mm intervals were obtained through the prostate for thisetermination. Variseed v7.1 (Varian Medical Systems, Palolto, CA) was used for the dosimetric calculations. The seedsere identified and the prostate and J-pouch were contoured on

hese axial computed tomography slices so that the D90, V100,nd R100 could be determined.

Pre- and postoperative bowel symptoms were evaluated bothubjectively by patient history and objectively using the Ex-

Table 1. Demographic and clinical parameters

PatientAge(y)

PSA(ng/mL)

GleasonScore

1 48 5.2 3�3�62 67 14 3�4�73 70 3.4 3�4�74 55 6.9 3�3�65 58 9.2 4�4�8

ADT � androgen deprivation therapy; PSA � prostate-specific ant

Table 2. Dosimetry outcomes

Patient D90 (%) V100 (%) V150 (%)

1 144.8 98.7 88.12 88.8 80.8 40.83 147.0 99.4 89.04 94.6 87.0 40.45 99.2 89.6 49.0

D90 � dose to 90% of the prostate; VX � prostate volume receiviof prescribed dose.

anded Prostate Cancer Index (EPIC) bowel function and s

70

other subscales3 preoperatively and at all follow-up visits.atients were asked to return for evaluation at 2 weeks, 3onths, 6 months, 9 months, and 12 months postoperatively.verages of continuous variables were calculated as means with

tandard deviation using descriptive statistics.

ESULTSive patients (mean age, 59.6 years) were identified asndergoing prostate brachytherapy after proctocolectomyith IPAA reconstruction. In all patients, colonic recon-

truction had been performed for ulcerative colitis refrac-ory to medical management. These patients underwentrostate brachytherapy at a mean of 6.3 years after theirroctocolectomy. All patients were diagnosed with T1Crostate cancer with a mean PSA value of 7.7 ng/mLrange, 5.2-14 ng/mL) and a Gleason score ranging from

to 8 (Table 1). Mean prostate volume on transrectalltrasound examination performed at the time of therocedure was 42.7 cm3 (median, 33.6 cm3; range, 23.3-5.2 cm3). The isotope 125I was used in 3 patients with aean total number of seeds of 104.3, a mean seed activity

f 0.294 mCi, and a mean total activity of 30.7 mCi. Thesotope 131Cs was used in the 2 most recent patients, with

mean total number of seeds of 105, a mean seedctivity of 2 IU, and a mean total activity of 210 IU,ecause our program began using cesium rather thanodine isotopes in September 2006. Postoperative do-imetry calculations (Table 2) revealed a mean D90 of14.9%, a mean V100 of 91.1%, and a mean R100 of.76 mL. Mean follow-up was 2.9 years (median, 3.0ears; range, 9 months to 5.6 years).

No patient has had biochemical relapse to date. Oneatient died of causes unrelated to his prostate cancerith an undetectable PSA value 36 months after under-oing prostate brachytherapy. The 2 most recent patientsave undetectable or declining PSA values, despite

me3)

NeoadjuvantTherapy

Follow-Up(y)

Last PSA(ng/mL)

6 None 5.6 �0.13 ADT 4.4 �0.15 ADT 3.0 �0.12 None 0.9 1.99 ADT 0.8 �0.1

0 (%) R100 (cm3) R80 (cm3) R60 (cm3)

5.7 0.98 2.12 3.156.6 0.15 0.35 5.610.0 1.51 2.91 5.441.4 1.13 2.44 5.611.7 .01 .08 0.53

of the prescribed dose; RX � volume of ileal pouch receiving X%

Volu(cm

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horter follow-up.

UROLOGY 73 (2), 2009

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Preoperatively, patients reported a wide range of dailyowel frequency: �5 bowel movements (BM) per day inatients 1 and 2, 5-10 BM per day in patients 3 and 4,nd 10-15 BM per day in patient 5. When reassessed 2eeks postoperatively, daily bowel frequency had in-reased to 7-9 BM per day in patient 1, to 10-15 BM peray in patients 2, 3, and 4, and to �15 BM per day inatient 5. However, at their 3-month postoperative visit,atients 1-4 reported that their bowel frequency hadeturned to preoperative baseline levels. Patient 5 sub-ectively reported that his bowel pattern returned toaseline by 4 months after his procedure.In 2 patients (patients 4 and 5), both of whom under-

ent brachytherapy with 131Cs, bowel function andother scores were assessed prospectively using the EPICurvey (Table 3). For both of these patients, 2-weekostoperative EPIC bowel function and bother subscalesevealed an acute worsening of bowel habits when com-ared with preoperative values. Bowel scores at 3 monthseflected a return to baseline in the first patient to un-ergo cesium brachytherapy. However, bowel scores inhe second cesium patient remained much lower thanreoperative values 3 months after the procedure. At theime of this patient’s next visit 12 months after hisrostate brachytherapy, he reported that his bowel pat-ern had not returned to baseline until 4 months after hisrocedure. This patient’s bowel scores on the EPIC sur-ey were improved at 12 months after his procedurehen compared with his preoperative baseline scores.

nterestingly, rectal dose was much higher in the sec-nd cesium patient when compared with the first ce-ium patient, and his prostate volume was much larger85.2 mL). In addition to the second cesium patientxperiencing a slightly longer time to return to base-ine than the first cesium patient, the amount of de-line in EPIC bowel scores at 2 weeks was muchreater for the second cesium patient when compared

Table 3. Pre- and postoperative bowel symptoms as mea-sured by the EPIC survey

Time of Survey EPIC ItemPatient

4Patient

5

Preoperative Bowel Summary 89.9 51.8Bowel Function 75.0 64.3Bowel Bother 92.9 39.3

2 wk postoperative Bowel Summary 37.5 7.1Bowel Function 35.7 7.1Bowel Bother 39.3 7.1

3 mo postoperative Bowel Summary 85.7 26.8Bowel Function 78.6 21.4Bowel Bother 92.8 32.1

6 mo postoperative Bowel Summary 87.3Bowel Function 82.1 N/ABowel Bother 96.4

12 mo postoperative Bowel Summary 64.3Bowel Function N/A 71.4Bowel Bother 57.1

EPIC � Expanded Prostate Cancer Index; N/A � not available.

ith the first cesium patient. c

ROLOGY 73 (2), 2009

Patients in the present study have not had clinical orndoscopic evidence of pouchitis. One patient developedposterolateral perianal abscess and fistula more than 5

ears after prostate brachytherapy, requiring incision andrainage followed by set-on placement. This complica-ion was not thought to be due to his prostate brachy-herapy given the location of the abscess, his lack ofther bowel symptomatology, the normal appearance ofhe anterior wall of the J-pouch near the prostate onndoscopy, and the fact that the abscess had no connec-ion to the J-pouch. No other rectal complications oc-urred in this cohort.

OMMENTleal pouch–anal anastomosis is a standard option in thelective surgical management of patients requiring totalroctocolectomy, providing complete excision of thearge intestine with transanal continent defecation ando external stoma.4 The 2 conditions for which IPAA isost commonly performed are ulcerative colitis and fa-ilial adenomatous polyposis; less common indications

nclude severe constipation due to colonic and rectalnertia, and Hirschsprung’s disease.5 With careful patientelection, IPAA is now performed as a single-stage pro-edure without ileostomy diversion,6 and successful out-omes have been reported with laparoscopic and hand-ssisted techniques.7

Although a majority of patients report a marked im-rovement of their quality of life after pouch surgery,owel function is not always ideal after IPAA. Severaltudies report that patients with an IPAA have an aver-ge of 6 BM per day. Some degree of fecal incontinencexists in 50% of patients after IPAA.8,9 These studiesemonstrate that bowel function can be tenuous afterreation of an IPAA. Pouchitis, an inflammatory condi-ion of the continent reservoir, is one of the most fre-uent long-term complications after IPAA and whenhronic has been shown to decrease health-related qual-ty of life.10 Although the etiology remains unclear, anmbalance between proinflammatory and anti-inflamma-ory cytokines may contribute to the development ofouchitis, which chronically affects 5%-10% of patientsndergoing IPAA reconstruction.5

The presence of an IPAA in men diagnosed withlinically localized prostate cancer makes their treatmentecision even more difficult. The difficulty of radicalrostatectomy is increased in the presence of an IPAAwing to loss of the normal tissue planes because ofnflammation and scarring.1 This loss of tissue planesaises the concern for injury to the pouch and resultingesico-pouch fistula. The risk of urinary incontinence isncreased in men with an IPAA who undergo radicalrostatectomy because of the denervation of the pelvicusculature occurring during resection of the rectum.dditionally, the ability to spare the neurovascular bun-

les may be diminished in men who have undergone

reation of an IPAA.

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Inflammatory bowel disease (IBD) also presents a prob-em for patients considering external beam radiation asheir treatment for prostate cancer. Willett et al.2 re-orted a 46% severe toxicity rate in a series of 28 patientsith IBD treated with abdominal and pelvic externaleam radiation for abdominal and pelvic neoplasms.herefore, IBD has been a relative contraindication toxternal beam radiotherapy in the management of pelvicalignancies. The presence of an IPAA is also a relative

ontraindication to external beam radiotherapy in menith clinically localized prostate cancer. In cases of IPAAerformed for ulcerative colitis, the bowel wall has al-eady been compromised by chronic inflammation anday be at increased risk for radiation damage due to

adiation-related vascular compromise, ischemia, and theroduction of oxygen radicals.11 In addition, the smallowel creating the J-pouch that would now be in therradiated field is much more sensitive to external beamadiotherapy. Although irradiating a large volume of rec-um places patients at risk, as long as �50% of theectum receives �50 Gy, the risk of permanent rectalall damage should be minimal.12 With small bowel,owever, treatment of any volume over doses of 50-54y places the patient at risk for radiation enteritis.13

ecause small bowel has lower tolerance for externaleam radiotherapy than large bowel, external beam ra-iotherapy after proctocolectomy and IPAA reconstruc-ion may increase the risk of pouchitis and decreaseuality of life.

With a reported incidence of grade 1 and 2 rectaloxicity at 8 months of 9.5%, prostate brachytherapy isell tolerated in patients with native rectums, and the

isk of serious rectal injury is rare.14 However, there iscarce literature describing prostate brachytherapy in pa-ients at high risk for rectal/bowel toxicity. Initial reportsescribing low-dose prostate brachytherapy in patientsith medically managed IBD have reported encouraging

esults with regard to rectal toxicity and cancer con-rol.15,16 Peters et al.16 reported an 81% 5-year actuarialreedom from developing late grade 2 rectal toxicity in 24atients with a history of IBD treated with prostaterachytherapy and speculated that symptom control waselated to a decrease in the surface area radiated. Thisypothesis supports our observation that the patient whouffered from the most severe postoperative symptomsad (by far) the largest prostate volume of 85.2 mL. Inhe present series, although all patients reported an in-rease in bowel frequency during the immediate postop-rative period, these symptoms returned to baseline levelsy 3 to 4 months after the procedure. No patients devel-ped serious complications of the pouch, such as ulcers orstulas.Treatment planning was not altered in the present

ohort in an attempt to decrease radiation to the pouch.adiation to the pouch as measured by R100, however,as quite acceptable. The length of patient follow-up

oes not allow for a meaningful estimate of biochemical

72

reedom from disease in the present cohort. However,osimetry has been demonstrated to be a surrogate forong-term cancer control after prostate brachytherapy.osimetry parameters in all men in the cohort were

cceptable, which in conjunction with promising PSAutcomes will, it is hoped, translate into long-term bio-hemical freedom from disease.

Weaknesses of the present study include the smallample size, retrospective nature, and that only 2 menad formal, prospective evaluation of their bowel func-ion. However, all men included in the study describedheir bowel symptoms as unchanged when compared withheir preoperative bowel symptoms, and no patients haderious pouch sequelae after their procedure.

ONCLUSIONSrostate brachytherapy seems to be a viable treatmentption for men who are diagnosed with clinically local-zed prostate cancer and who have undergone creation ofn IPAA. Radiation-induced pouch toxicity was self-imited, and no serious pouch sequelae were encountered.lthough follow-up in our series is too short to reliably

etermine ultimate biochemical outcomes, adequate do-imetry outcomes were obtained and preliminary PSAutcomes are promising.

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have failed radiation therapy or cryotherapy as primary treatmentfor prostate cancer. Urology. 2003;62(suppl 1):69-78.

2. Willett CG, Ooi CJ, Zietman AL, et al. Acute and late toxicity ofpatients with inflammatory bowel disease undergoing irradiation forabdominal and pelvic neoplasms. Int J Radiat Oncol Biol Phys.2000;46:995-998.

3. Dahm P, Silverstein AD, Weizer AZ, et al. A longitudinalassessment of bowel related symptoms and fecal incontinencefollowing radical perineal prostatectomy. J Urol. 2003;169:2220-2224.

4. Parks AG, Nicholls RJ. Proctocolectomy without ileostomy forulcerative colitis. Br Med J. 1978;2:85-88.

5. McGuire BB, Brannigan AE, O’Connell PR. Ileal pouch-anal anas-tomosis. Br J Surg. 2007;94:812-823.

6. Remzi FH, Fazio VW, Gorgun E, et al. The outcome after restor-ative proctocolectomy with or without defunctioning ileostomy.Dis Colon Rectum. 2006;49:470-477.

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8. Ferrante M, Declerck S, De Hertogh G, et al. Outcome afterproctocolectomy with ileal pouch-anal anastomosis for ulcerativecolitis. Inflamm Bowel Dis. 2007;14:20-28.

9. Michelassi F, Stella M, Block GE. Prospective assessment of func-tional results after ileal J pouch-anal restorative proctocolectomy.Arch Surg. 1993;128:889-894; discussion 894-885.

0. Pemberton JH, Kelly KA, Beart RW Jr, et al. Ileal pouch-analanastomosis for chronic ulcerative colitis. Long-term results. AnnSurg. 1987;206:504-513.

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3. Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue totherapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109-122.

4. Gelblum DY, Potters L. Rectal complications associated with trans-perineal interstitial brachytherapy for prostate cancer. Int J Radiat

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