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Oncology
Low-dose-rate Brachytherapy as SalvageTreatment of Local Prostate CancerRecurrence After Radical ProstatectomyKrystyna Traudt, Jay Ciezki, and Eric A. Klein
OBJECTIVES To present our initial experience with brachytherapy used as a salvage procedure for localrecurrence of prostate cancer in the prostatic fossa after radical prostatectomy.
METHODS The patients included 5 consecutive men who underwent brachytherapy as a salvage procedureafter radical prostatectomy from December 2006 to March 2008. We used a technique ofimplanting the local recurrences similar to the American Brachytherapy Society Guidelines forimplanting an intact prostate as definitive therapy.1 Two modifications were made related to therecurrence location: a rare need to manage urethral doses because the recurrence was typicallyperirectal, and more aggressive management of the dose to the rectum because of this proximity.
RESULTS All patients tolerated the brachytherapy procedure well and showed a decline in the prostate-specific antigen level, with a median nadir of 0.72 ng/mL at a median follow-up of 13 months.The postprocedural symptoms were minor and included limited new-onset urgency. At the lastfollow-up visit, all patients had prostate-specific antigen doubling times, which have beenassociated with long median survival times.
CONCLUSIONS Salvage brachytherapy for biopsy-proven local recurrence of prostate cancer is a technicallyfeasible alternative to external beam radiotherapy for local control of recurrences in the prostaticfossa in selected patients after radical prostatectomy. UROLOGY 77: 1416–1419, 2011. © 2011
Elsevier Inc.dc
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Since the late 1970s, radical retropubic prostatectomyhas been accepted as an effective definitive therapyfor localized carcinoma of the prostate; however,
0% of men with organ-confined disease will experienceecurrence within 10 years of therapy.2,3 This recurrence
rate increased to 40% in men with extraprostatic extensionand positive surgical margins.1 Most of these recurrencesevelop as biochemical failure in which no histologic evi-ence of disease can be detected in the prostatic fossa.4
Traditionally, prostate cancer recurrences have been man-aged with external beam radiotherapy or androgen depriva-tion therapy; however, both of these salvage treatmentmodalities carry significant risks of adverse side effects. Pa-tients undergoing external beam radiotherapy can experi-ence genitourinary, gastrointestinal, and sexual side effectsowing to irradiation of the bladder, neurovascular bundles,and rectum during treatment.5 Androgen deprivation ther-py has been shown to increase the risk of sarcopenia, sexual
From the Case Western Reserve University School of Medicine, Cleveland, Ohio;Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleve-land, Ohio; and Glickman Urologic and Kidney Institute, Cleveland Clinic, Cleveland,Ohio
Reprint requests: Eric A. Klein, M.D., Glickman Urologic and Kidney Institute,Cleveland Clinic, Desk Q10, 9500 Euclid Ave, Cleveland, OH 44195. E-mail:
[email protected]Submitted: November 15, 2010, accepted (with revisions): February 9, 2011
1416 © 2011 Elsevier Inc.All Rights Reserved
ysfunction, loss of lean body mass, glucose intolerance, andardiovascular 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 conveniencef brachytherapy, because it is performed as a single-day,utpatient procedure. Although low-dose-rate brachyther-py has traditionally been used as primary therapy for low-nd intermediate-risk prostate cancer, we present our initialxperience with brachytherapy used as a salvage procedureor 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 by0090-4295/11/$36.00doi:10.1016/j.urology.2011.02.011
tdapopeaciwpttpcVansod�bsn1st
digital rectal examination, ultrasonography, and abdominal andpelvic computed tomography, and the patients were selectedbecause of a favorable location of the recurrence anterior to therectum and not involving the bladder (Fig. 1). Some patientsalso underwent bone scans at the discretion of the treatingphysician; however, none had evidence of distant metastases.Patients received no additional therapy before or after thesalvage brachytherapy procedure. Iodine-125 sources were usedin all procedures.
Dosimetry and Implant TechniqueWe used a technique of implanting the local recurrences similar tothe American Brachytherapy Society Guidelines for implanting anintact prostate as definitive therapy,10 with 2 modifications relatedo the recurrence location: (a) a rare need to manage urethraloses, because the recurrence was typically perirectal, and (b) moreggressive management of the dose to the rectum because of thisroximity. Specifically, we kept the rectal volume receiving 100%f the prescribed dose �1 cm3, in keeping with standard intact-rostate brachytherapy practices. The patients were placed in thexaggerated dorsal lithotomy position, the rectum was irrigated,nd a transrectal ultrasound probe was placed in the rectum ac-ording to the typical prostate implant procedure. When acquiringmages for planning, the superior and inferior extents of the noduleere identified first. The first axial section to be imported into thelanning system was 1 cm superior to the most superior extent ofhe nodule. The last axial section to be imported was 1 cm distalo the most inferior extent of the nodule. The sources werelanned according to the grid pattern commonly available on mostommercial planning software packages (VariSeed, version 7.1,arian Medical Systems, Palo Alto, CA). The source array mimicsbowl covering an apple on a table. The apple would represent theodule, with the bowl representing the source array. The bowl, orource array, covers the apple, or nodule, as it sits on the table, oruter rectal wall. In this manner, a minimal dose of 144 Gy can beelivered while limiting the rectal volume receiving the dose to1 cm3 (Fig. 2). In all cases, the nodule was identified and
iopsied using transrectal ultrasound guidance in the office. Thisame biopsy target was contoured, without a margin, in the plan-ing software as the treatment target to be encompassed by the44-Gy isodose line. Except for perirectal sources, all sources weretranded or linked (Oncura RAPID Strand [Oncura Inc., Arling-
Figure 1. Scan showing prostate cancer recurrence (arrow).
on Heights, IL] or CR Bard RediLink [Bard Inc., Medical Divi-
UROLOGY 77 (6), 2011
sion, Covington, GA], respectively). The activity per source wasno different that our usual activity used for intact prostate brachy-therapy (range 0.35-0.47 U/source). The insertion of the needlescarrying the sources was performed in a manner identical to atypical prostate implantation procedure.
RESULTSThe pretreatment characteristics of the 5 patients are listedin Table 1. The median age at salvage brachytherapy for thecohort was 77 years, and the median interval from prosta-tectomy to salvage brachytherapy was 8 years. The prepro-statectomy pathologic features included a median PSA levelof 6.3 ng/mL and a median Gleason score of 7. The patho-logic characteristics of recurrent lesions included a medianPSA level of 4.73 ng/mL and median Gleason score of 7.
The post-therapy characteristics are listed in Table 2. Allpatients tolerated the brachytherapy procedure well andshowed a decline in the PSA level at follow-up. One patientexperienced minor new-onset urgency postoperatively.Three patients reported organic impotence before the pro-cedure. This was unchanged in postprocedural follow-up.Patients reported no additional sexual side effects or lowerurinary tract symptoms, and no urethral or rectal injuriesoccurred. After salvage brachytherapy, all patients had adecline in the PSA level, with a median nadir value of 0.72ng/mL at median follow-up of 13 months. At the lastfollow-up visit, all patients had PSA doubling times that areassociated with a long median survival time.
The postoperative quality assessment was performed sim-ilar to the American Brachytherapy Society guidelines forintact prostates.2,11 Figure 3 demonstrates the dose distribu-tion achieved during postimplantation planning at 1 monthafter a typical procedure. The nodular recurrence was well-subtended by the prescription line and the dose to therectum and bladder was minimal (actual values listed inTable 2).
COMMENTWe present an initial experience with salvage low-dose-rate brachytherapy for local recurrence of prostate cancer
Figure 2. Software generated contour of nodule andplanned dosing.
after radical prostatectomy. All patients in the cohort
1417
l ultra
lume
ose
tolerated the procedure well and were alive at publica-tion. Although the presence of metastatic disease in
Table 1. Pretreatment characteristics
Variable 1 2
Age (y) 77 77Pre-RP PSA (ng/mL) 9.0 7.1Pre-RP Gleason score 7 7Pre-RP clinical stage T3bN0M0 T1cN0M0Pathologic stage pT3bN0M0 pT2NxM0Postoperative PSA nadir
(ng/mL)�0.2 �0.2
Interval to local recurrence(y)
14 0.5
Detection of recurrence Nodule palpableon DRE
CT and M
Size of recurrence onTRUS (cm)
0.7 � 1.8 2.7 � 2.5
Gleason score ofrecurrence
7 7
PSA at recurrence (ng/mL) 4.73 4.5
Pt. No., patient number; RP, radical prostatectomy; PSA, prosttomography; MRI, magnetic resonance imaging; TRUS, transrecta
Table 2. Post-treatment characteristics
Variable 1
D90 of nodule (Gy) 207Rectal V100 (cm3) 0.07PSA nadir after treatment (ng/mL) 0.79Interval to PSA nadir (mo) 16PSA at last follow-up visit (ng/mL) 1.41Interval since treatment (mo) 42PSA DT since postimplant nadir (mo) 33
D90, minimal dose received by 90% of target volume; V100, voabbreviations as in Table 1.
Figure 3. D
these patients could not be completely ruled out, the
1418
follow-up data confirmed the PSA declines in all patients(median 0.72 ng/mL at nadir) after implantation, sug-
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
pecific antigen; DRE, digital rectal examination; CT, computedsonography.
Pt. No.
2 3 4 5
155 121 140 1180.10 0.00 0.01 0.00
�0.03 0.86 1.05 0.7244 13 7 7�0.03 0.86 1.05 1.1644 25 7 30
0 0 0 8.8
receiving 100% of prescribed dose; DT, doubling time; other
distribution.
RI
� 4
6
ate-s
gesting that the major disease burden was localized. Fur-
UROLOGY 77 (6), 2011
isrt
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-ngful clinical benefit. The reported genitourinary andexual side effects were minor and infrequent and noectal toxicity occurred in the present series, in contrasto a study by MacDonald et al,13 who reported a 26% rate
of 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.
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delphia: Saunders Elsevier; 2004:959-1017.UROLOGY 77 (6), 2011
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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.
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