Low-dose-rate Brachytherapy as Salvage Treatment of Local Prostate Cancer Recurrence After Radical Prostatectomy

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  • Oncology

    L eT sR aKr

    OB ithprost

    ME mencemlar titiveanaeme

    RE apynadinostattim

    CO ovenadiol pro

    Elsevier Inc.

    S10recratandedeTragetiomotieenowanap

    FroDeplandOhiR

    ClekleinS

    14ince the late 1970s, radical retropubic prostatectomyhas been accepted as an effective definitive therapyfor localized carcinoma of the prostate; however,

    % of men with organ-confined disease will experienceurrence within 10 years of therapy.2,3 This recurrencee increased to 40% in men with extraprostatic extensiond positive surgical margins.1 Most of these recurrencesvelop as biochemical failure in which no histologic evi-nce of disease can be detected in the prostatic fossa.4

    aditionally, prostate cancer recurrences have been man-d with external beam radiotherapy or androgen depriva-n therapy; however, both of these salvage treatmentdalities carry significant risks of adverse side effects. Pa-nts undergoing external beam radiotherapy can experi-ce genitourinary, gastrointestinal, and sexual side effectsing to irradiation of the bladder, neurovascular bundles,d rectum during treatment.5 Androgen deprivation ther-y has been shown to increase the risk of sarcopenia, sexual

    dysfunction, loss of lean body mass, glucose intolerance, andcardiovascular events.6,7

    In recent years, image-guided brachytherapy has emergedas another form of primary monotherapy for localized pros-tate cancer, allowing patients who are not surgical candi-dates or who might favor a less-invasive treatment modalityto still seek curative therapy.8 In general, low-dose-ratebrachytherapy confers fewer side effects than external beamradiotherapy or androgen deprivation and does so at a lowercost to patients.9 Patients also benefit from the convenienceof brachytherapy, because it is performed as a single-day,outpatient procedure. Although low-dose-rate brachyther-apy has traditionally been used as primary therapy for low-and intermediate-risk prostate cancer, we present our initialexperience with brachytherapy used as a salvage procedurefor local recurrence after radical prostatectomy.

    MATERIAL AND METHODS

    Patient SelectionWe report on 5 consecutive patients who had undergonebrachytherapy as a salvage procedure after local recurrence ofprostate cancer in the prostatic fossa after radical prostatectomyfrom December 2006 to March 2008. The initial surgical ap-proaches included 3 patients who had undergone radical retro-pubic prostatectomy, radical perineal prostatectomy, and ro-botic prostatectomy. All recurrences were documented by

    m the Case Western Reserve University School of Medicine, Cleveland, Ohio;artment of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleve-, Ohio; and Glickman Urologic and Kidney Institute, Cleveland Clinic, Cleveland,oeprint requests: Eric A. Klein, M.D., Glickman Urologic and Kidney Institute,veland Clinic, Desk Q10, 9500 Euclid Ave, Cleveland, OH 44195. E-mail:e@ccf.orgubmitted: November 15, 2010, accepted (with revisions): February 9, 2011

    16 2011 Elsevier Inc. 0090-4295/11/$36.00ow-dose-rate Brachythreatment of Local Proecurrence After Radicystyna Traudt, Jay Ciezki, and Eric A. Klein

    JECTIVES To present our initial experience wrecurrence of prostate cancer in the

    THODS The patients included 5 consecutiveafter radical prostatectomy from Deimplanting the local recurrences simiimplanting an intact prostate as definrecurrence location: a rare need to mperirectal, and more aggressive manag

    SULTS All patients tolerated the brachytherspecific antigen level, with a medianThe postprocedural symptoms were mfollow-up visit, all patients had proassociated with long median survival

    NCLUSIONS Salvage brachytherapy for biopsy-prfeasible alternative to external beam rfossa in selected patients after radicaAll Rights Reservedrapy as Salvagetate Cancerl Prostatectomy

    brachytherapy used as a salvage procedure for localatic fossa after radical prostatectomy.who underwent brachytherapy as a salvage procedureber 2006 to March 2008. We used a technique ofo the American Brachytherapy Society Guidelines fortherapy.1 Two modifications were made related to thege urethral doses because the recurrence was typicallynt of the dose to the rectum because of this proximity.procedure well and showed a decline in the prostate-ir of 0.72 ng/mL at a median follow-up of 13 months.r and included limited new-onset urgency. At the laste-specific antigen doubling times, which have beenes.local recurrence of prostate cancer is a technically

    therapy for local control of recurrences in the prostaticstatectomy. UROLOGY 77: 14161419, 2011. 2011doi:10.1016/j.urology.2011.02.011

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    URital rectal examination, ultrasonography, and abdominal andvic computed tomography, and the patients were selectedause of a favorable location of the recurrence anterior to thetum and not involving the bladder (Fig. 1). Some patientso underwent bone scans at the discretion of the treatingysician; however, none had evidence of distant metastases.tients received no additional therapy before or after thevage brachytherapy procedure. Iodine-125 sources were usedall procedures.

    simetry and Implant Techniqueused a technique of implanting the local recurrences similar toAmerican Brachytherapy Society Guidelines for implanting anact prostate as definitive therapy,10 with 2 modifications relatedthe recurrence location: (a) a rare need to manage urethrales, because the recurrence was typically perirectal, and (b) moreressive management of the dose to the rectum because of thisximity. Specifically, we kept the rectal volume receiving 100%the prescribed dose 1 cm3, in keeping with standard intact-state brachytherapy practices. The patients were placed in theggerated dorsal lithotomy position, the rectum was irrigated,a transrectal ultrasound probe was placed in the rectum ac-

    ding to the typical prostate implant procedure. When acquiringages for planning, the superior and inferior extents of the nodulere identified first. The first axial section to be imported into thenning system was 1 cm superior to the most superior extent ofnodule. The last axial section to be imported was 1 cm distalthe most inferior extent of the nodule. The sources werenned according to the grid pattern commonly available on mostmercial planning software packages (VariSeed, version 7.1,

    rian Medical Systems, Palo Alto, CA). The source array mimicsowl covering an apple on a table. The apple would represent thedule, with the bowl representing the source array. The bowl, orrce array, covers the apple, or nodule, as it sits on the table, orer rectal wall. In this manner, a minimal dose of 144 Gy can beivered while limiting the rectal volume receiving the dose tocm3 (Fig. 2). In all cases, the nodule was identified and

    psied using transrectal ultrasound guidance in the office. Thise biopsy target was contoured, without a margin, in the plan-g software as the treatment target to be encompassed by the-Gy isodose line. Except for perirectal sources, all sources werended or linked (Oncura RAPID Strand [Oncura Inc., Arling-Heights, IL] or CR Bard RediLink [Bard Inc., Medical Divi-

    igure 1. Scan showing prostate cancer recurrence (arrow).OLOGY 77 (6), 2011n, Covington, GA], respectively). The activity per source wasdifferent that our usual activity used for intact prostate brachy-rapy (range 0.35-0.47 U/source). The insertion of the needlesrying the sources was performed in a manner identical to aical prostate implantation procedure.

    SULTSe pretreatment characteristics of the 5 patients are listedTable 1. The median age at salvage brachytherapy for thehort was 77 years, and the median interval from prosta-tomy to salvage brachytherapy was 8 years. The prepro-tectomy pathologic features included a median PSA level6.3 ng/mL and a median Gleason score of 7. The patho-ic characteristics of recurrent lesions included a medianA level of 4.73 ng/mL and median Gleason score of 7.The post-therapy characteristics are listed in Table 2. Alltients tolerated the brachytherapy procedure well andwed a decline in the PSA level at follow-up. One patientperienced minor new-onset urgency postoperatively.ree patients reported organic impotence before the pro-ure. This was unchanged in postprocedural follow-up.tients reported no additional sexual side effects or lowernary tract symptoms, and no urethral or rectal injuriescurred. After salvage brachytherapy, all patients had acline in the PSA level, with a median nadir value of 0.72/mL at median follow-up of 13 months. At the lastlow-up visit, all patients had PSA doubling times that areociated with a long median survival time.The postoperative quality assessment was performed sim-r to the American Brachytherapy Society guidelines foract prostates.2,11 Figure 3 demonstrates the dose distribu-n achieved during postimplantation planning at 1 monther a typical procedure. The nodular recurrence was well-tended by the prescription line and the dose to thetum and bladder was minimal (actual values listed inble 2).

    MMENTe present an initial experience with salvage low-dose-e brachytherapy for local recurrence of prostate cancerer radical prostatectomy. All patients in the cohort

    ure 2. Software generated contour of nodule andnned dosing.1417

  • toltiothe

    Table 1. Pretreatment characteristics

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    14erated the procedure well and were alive at publica-n. Although the presence of metastatic disease inse patients could not be completely ruled out, the

    riable 1 2

    e (y) 77 77e-RP PSA (ng/mL) 9.0 7.1e-RP Gleason score 7 7e-RP clinical stage T3bN0M0 T1cN0M0thologic stage pT3bN0M0 pT2NxM0stoperative PSA nadir(ng/mL)

    0.2 0.2

    terval to local recurrence(y)

    14 0.5

    tection of recurrence Nodule palpableon DRE

    CT and MRI

    ze of recurrence onTRUS (cm)

    0.7 1.8 2.7 2.5

    eason score ofrecurrence

    7 7

    A at recurrence (ng/mL) 4.73 4.56

    . No., patient number; RP, radical prostatectomy; PSA, prostatmography; MRI, magnetic resonance imaging; TRUS, transrectal u

    ble 2. Post-treatment characteristics

    riable 1

    0 of nodule (Gy) 207ctal V100 (cm

    3) 0.07A nadir after treatment (ng/mL) 0.79terval to PSA nadir (mo) 16A at last follow-up visit (ng/mL) 1.41terval since treatment (mo) 42A DT since postimplant nadir (mo) 33

    0, minimal dose received by 90% of target volume; V100, volubreviations as in Table 1.

    Figure 3. Dos18low-up data confirmed the PSA declines in all patientsedian 0.72 ng/mL at nadir) after implantation, sug-ting that the major disease burden was localized. Fur-

    Pt. No.

    3 4 5

    63 64 77Unknown 5.5 5.4Unknown 8 6Unknown T1cN0M0 T1cN0M0Unknown pT2N0M0 pT2NxM0

    0.2 0.2 0.2

    12 2 8

    Nodule palpableon DRE

    Nodule palpableon DRE

    Nodule palpableon DRE

    2.5 4 2.5 4.3 1.2 1.8

    7 8 7

    6.5 2.2 6.0

    cific antigen; DRE, digital rectal examination; CT, computednography.

    Pt. No.

    2 3 4 5

    5 121 140 1180.10 0.00 0.01 0.000.03 0.86 1.05 0.724 13 7 70.03 0.86 1.05 1.164 25 7 300 0 0 8.8

    ceiving 100% of prescribed dose; DT, doubling time; other

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    15UROLOGY 77 (6), 2011

  • thermore, the PSA doubling times at the last follow-upvisit for all patients were at rates associated with a lowrisk of clinically detectable metastatic disease at 5 yearsand a median survival of 5 years,12 suggesting mean-ingful clinical benefit. The reported genitourinary andsexual side effects were minor and infrequent and norectal toxicity occurred in the present series, in contrastto a study by MacDonald et al,13 who reported a 26% rateof chronic gastrointestinal toxicity and 24% chronic gen-itourinary toxicity after salvage external beam radiother-apy in 34 patients treated for similar palpable local re-currences.

    CONCLUSIONSOur initial experience with the use of salvage brachy-therapy in 5 patients with biopsy-proven local recur-rences has demonstrated its technical feasibility and po-tential as an alternative to external beam radiotherapyfor local control of recurrence in the prostatic fossa inselected patients after radical prostatectomy. The nearabsence of gastrointestinal and genitourinary toxicitycompares favorably with the toxicity rates generally seenafter salvage external beam radiotherapy, with additionaladvantages of lower cost and patient convenience.

    References1. Nag S, Beyer D, Friedland J, et al. American Brachytherapy Society

    (ABS) recommendations for transperineal placement brachytherapy

    2.

    3. Catalona WJ, Han M. Definitive therapy for localized prostatecanceran overview. In: Wein AJ, Kavoussi LR, Peters CA, et al,eds. Campbell-Walsh Urology, 9th ed. Philadelphia: SaundersElsevier; 2007.

    4. Eastham J, Scardino P. Radical prostatectomy. In: Walsh PC, RetikAB, Vaughan E, et al, eds. Campbells Urology, 8th ed. Philadelphia:Saunders Elsevier; 2002:3080-3106.

    5. DAmico A, Crook J, Beard CJ, et al. Radiation therapy forprostate cancer. In: Walsh PC, Retik AB, Vaughan E, et al, eds.Campbells Urology, 8th ed. Philadelphia: Saunders Elsevier;2002:3147-3170.

    6. Green H, Pakenham K, Headley B, et al. Quality of life comparedduring pharmacological treatments and clinical monitoring fornon-localized prostate cancer: a randomized controlled trial. BJUInt. 2004;93:975-979.

    7. Smith MR. Changes in fat and lean body mass during androgen-deprivation therapy for prostate cancer. Urology. 2004;63:742-745.

    8. Potters L, Morgenstern C, Calugaru E. 12-Year outcomes followingpermanent prostate brachytherapy in patients with clinically local-ized prostate cancer. J Urol. 2005;173:1562-1566.

    9. Vigneri P, Herati AS, Potters L. The second decade of prostatebrachytherapy: evidence and cost based outcomes. Urol Oncol Se-min Orig Investig. 2010;28:86-90.

    10. Nag S, Beyer D, Friedland J, et al. American Brachytherapy Society(ABS) recommendations for transperineal placement brachyther-apy of prostate cancer. Int J Radiat Oncol Biol Phys. 1999;44:789-799.

    11. Nag S, Bice W, DeWyngaert JK, et al. The American Brachyther-apy Society recommendations for permanent prostate brachyther-apy postimplant dosimetric analysis. Int J Radiat Oncol Biol Phys.2000;46:221-230.

    12. Lee A, DAmico A. Utility of prostate-specific antigen kinetics inaddition to clinical factors in the selection of patients for salvage

    13.

    URof prostate cancer. Int J Radiat Oncol Biol Phys. 1999;44:789-799.Leibel TL, Phillips SA. Cancer of the Prostate. In: Phillips SA,Leibel TL, eds. Textbook of Radiation Oncology, 2nd ed. Phila-delphia: Saunders Elsevier; 2004:959-1017.OLOGY 77 (6), 2011local therapy. J Clin Oncol. 2005;23):8192-8197.MacDonald OK, Schild SE, Vora SA, et al. Salvage radiotherapyfor palpable, locally recurrent prostate cancer after radical prosta-tectomy. Int J Radiat Oncol Biol Phys. 2004;58:1530-1535.1419

    Low-dose-rate Brachytherapy as Salvage Treatment of Local Prostate Cancer Recurrence After Radic ...Material and MethodsPatient SelectionDosimetry and Implant Technique

    ResultsCommentConclusionsReferences

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