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

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

Oncology Low-dose-rate Brachytherapy as Salvage Treatment of Local Prostate Cancer Recurrence After Radical Prostatectomy Krystyna Traudt, Jay Ciezki,...

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Oncology Low-dose-rate Brachytherapy as Salvage Treatment of Local Prostate Cancer Recurrence After Radical Prostatectomy Krystyna Traudt, Jay Ciezki, and Eric A. Klein OBJECTIVES METHODS

RESULTS

CONCLUSIONS

To present our initial experience with brachytherapy used as a salvage procedure for local recurrence of prostate cancer in the prostatic fossa after radical prostatectomy. The patients included 5 consecutive men who underwent brachytherapy as a salvage procedure after radical prostatectomy from December 2006 to March 2008. We used a technique of implanting the local recurrences similar to the American Brachytherapy Society Guidelines for implanting an intact prostate as definitive therapy.1 Two modifications were made related to the recurrence location: a rare need to manage urethral doses because the recurrence was typically perirectal, and more aggressive management of the dose to the rectum because of this proximity. All patients tolerated the brachytherapy procedure well and showed a decline in the prostatespecific 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 last follow-up visit, all patients had prostate-specific antigen doubling times, which have been associated with long median survival times. Salvage brachytherapy for biopsy-proven local recurrence of prostate cancer is a technically feasible alternative to external beam radiotherapy for local control of recurrences in the prostatic fossa in selected patients after radical prostatectomy. UROLOGY 77: 1416 –1419, 2011. © 2011 Elsevier Inc.

S

ince the late 1970s, radical retropubic prostatectomy has been accepted as an effective definitive therapy for localized carcinoma of the prostate; however, 10% of men with organ-confined disease will experience recurrence within 10 years of therapy.2,3 This recurrence rate increased to 40% in men with extraprostatic extension and positive surgical margins.1 Most of these recurrences develop as biochemical failure in which no histologic evidence of disease can be detected in the prostatic fossa.4 Traditionally, prostate cancer recurrences have been managed with external beam radiotherapy or androgen deprivation therapy; however, both of these salvage treatment modalities carry significant risks of adverse side effects. Patients undergoing external beam radiotherapy can experience genitourinary, gastrointestinal, and sexual side effects owing to irradiation of the bladder, neurovascular bundles, and rectum during treatment.5 Androgen deprivation therapy has been shown to increase the risk of sarcopenia, sexual

dysfunction, loss of lean body mass, glucose intolerance, and cardiovascular events.6,7 In recent years, image-guided brachytherapy has emerged as another form of primary monotherapy for localized prostate cancer, allowing patients who are not surgical candidates or who might favor a less-invasive treatment modality to still seek curative therapy.8 In general, low-dose-rate brachytherapy confers fewer side effects than external beam radiotherapy or androgen deprivation and does so at a lower cost to patients.9 Patients also benefit from the convenience of brachytherapy, because it is performed as a single-day, outpatient procedure. Although low-dose-rate brachytherapy has traditionally been used as primary therapy for lowand intermediate-risk prostate cancer, we present our initial experience with brachytherapy used as a salvage procedure for local recurrence after radical prostatectomy.

MATERIAL AND METHODS Patient Selection

From the Case Western Reserve University School of Medicine, Cleveland, Ohio; Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, 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

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© 2011 Elsevier Inc. All Rights Reserved

We report on 5 consecutive patients who had undergone brachytherapy as a salvage procedure after local recurrence of prostate cancer in the prostatic fossa after radical prostatectomy from December 2006 to March 2008. The initial surgical approaches included 3 patients who had undergone radical retropubic prostatectomy, radical perineal prostatectomy, and robotic prostatectomy. All recurrences were documented by 0090-4295/11/$36.00 doi:10.1016/j.urology.2011.02.011

Figure 2. Software generated contour of nodule and planned dosing. Figure 1. Scan showing prostate cancer recurrence (arrow).

digital rectal examination, ultrasonography, and abdominal and pelvic computed tomography, and the patients were selected because of a favorable location of the recurrence anterior to the rectum and not involving the bladder (Fig. 1). Some patients also underwent bone scans at the discretion of the treating physician; however, none had evidence of distant metastases. Patients received no additional therapy before or after the salvage brachytherapy procedure. Iodine-125 sources were used in all procedures.

Dosimetry and Implant Technique We used a technique of implanting the local recurrences similar to the American Brachytherapy Society Guidelines for implanting an intact prostate as definitive therapy,10 with 2 modifications related to the recurrence location: (a) a rare need to manage urethral doses, because the recurrence was typically perirectal, and (b) more aggressive management of the dose to the rectum because of this proximity. Specifically, we kept the rectal volume receiving 100% of the prescribed dose ⬍1 cm3, in keeping with standard intactprostate brachytherapy practices. The patients were placed in the exaggerated dorsal lithotomy position, the rectum was irrigated, and a transrectal ultrasound probe was placed in the rectum according to the typical prostate implant procedure. When acquiring images for planning, the superior and inferior extents of the nodule were identified first. The first axial section to be imported into the planning system was 1 cm superior to the most superior extent of the nodule. The last axial section to be imported was 1 cm distal to the most inferior extent of the nodule. The sources were planned according to the grid pattern commonly available on most commercial planning software packages (VariSeed, version 7.1, Varian Medical Systems, Palo Alto, CA). The source array mimics a bowl covering an apple on a table. The apple would represent the nodule, with the bowl representing the source array. The bowl, or source array, covers the apple, or nodule, as it sits on the table, or outer rectal wall. In this manner, a minimal dose of 144 Gy can be delivered while limiting the rectal volume receiving the dose to ⱕ1 cm3 (Fig. 2). In all cases, the nodule was identified and biopsied using transrectal ultrasound guidance in the office. This same biopsy target was contoured, without a margin, in the planning software as the treatment target to be encompassed by the 144-Gy isodose line. Except for perirectal sources, all sources were stranded or linked (Oncura RAPID Strand [Oncura Inc., Arlington Heights, IL] or CR Bard RediLink [Bard Inc., Medical DiviUROLOGY 77 (6), 2011

sion, Covington, GA], respectively). The activity per source was no different that our usual activity used for intact prostate brachytherapy (range 0.35-0.47 U/source). The insertion of the needles carrying the sources was performed in a manner identical to a typical prostate implantation procedure.

RESULTS The pretreatment characteristics of the 5 patients are listed in Table 1. The median age at salvage brachytherapy for the cohort was 77 years, and the median interval from prostatectomy to salvage brachytherapy was 8 years. The preprostatectomy pathologic features included a median PSA level of 6.3 ng/mL and a median Gleason score of 7. The pathologic characteristics of recurrent lesions included a median PSA level of 4.73 ng/mL and median Gleason score of 7. The post-therapy characteristics are listed in Table 2. All patients tolerated the brachytherapy procedure well and showed a decline in the PSA level at follow-up. One patient experienced minor new-onset urgency postoperatively. Three patients reported organic impotence before the procedure. This was unchanged in postprocedural follow-up. Patients reported no additional sexual side effects or lower urinary tract symptoms, and no urethral or rectal injuries occurred. After salvage brachytherapy, all patients had a decline in the PSA level, with a median nadir value of 0.72 ng/mL at median follow-up of 13 months. At the last follow-up visit, all patients had PSA doubling times that are associated with a long median survival time. The postoperative quality assessment was performed similar to the American Brachytherapy Society guidelines for intact prostates.2,11 Figure 3 demonstrates the dose distribution achieved during postimplantation planning at 1 month after a typical procedure. The nodular recurrence was wellsubtended by the prescription line and the dose to the rectum and bladder was minimal (actual values listed in Table 2).

COMMENT We present an initial experience with salvage low-doserate brachytherapy for local recurrence of prostate cancer after radical prostatectomy. All patients in the cohort 1417

Table 1. Pretreatment characteristics

Variable Age (y) Pre-RP PSA (ng/mL) Pre-RP Gleason score Pre-RP clinical stage Pathologic stage Postoperative PSA nadir (ng/mL) Interval to local recurrence (y) Detection of recurrence Size of recurrence on TRUS (cm) Gleason score of recurrence PSA at recurrence (ng/mL)

1 77 9.0 7 T3bN0M0 pT3bN0M0 ⬍0.2

77 7.1 7 T1cN0M0 pT2NxM0 ⬍0.2

14 Nodule palpable on DRE 0.7 ⫻ 1.8

Pt. No. 3

2

4

63 Unknown Unknown Unknown Unknown ⬍0.2

0.5 CT and MRI 2.7 ⫻ 2.5 ⫻ 4

5

64 5.5 8 T1cN0M0 pT2N0M0 ⬍0.2

77 5.4 6 T1cN0M0 pT2NxM0 ⬍0.2

12

2

8

Nodule palpable on DRE 2.5 ⫻ 4

Nodule palpable on DRE 2.5 ⫻ 4.3

Nodule palpable on DRE 1.2 ⫻ 1.8

7

7

7

8

7

4.73

4.56

6.5

2.2

6.0

Pt. No., patient number; RP, radical prostatectomy; PSA, prostate-specific antigen; DRE, digital rectal examination; CT, computed tomography; MRI, magnetic resonance imaging; TRUS, transrectal ultrasonography.

Table 2. Post-treatment characteristics

Variable D90 of nodule (Gy) Rectal V100 (cm3) PSA nadir after treatment (ng/mL) Interval to PSA nadir (mo) PSA at last follow-up visit (ng/mL) Interval since treatment (mo) PSA DT since postimplant nadir (mo)

1

2

Pt. No. 3

207 0.07 0.79 16 1.41 42 33

155 0.10 ⬍0.03 44 ⬍0.03 44 0

121 0.00 0.86 13 0.86 25 0

4

5

140 0.01 1.05 7 1.05 7 0

118 0.00 0.72 7 1.16 30 8.8

D90, minimal dose received by 90% of target volume; V100, volume receiving 100% of prescribed dose; DT, doubling time; other abbreviations as in Table 1.

Figure 3. Dose distribution.

tolerated the procedure well and were alive at publication. Although the presence of metastatic disease in 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, suggesting that the major disease burden was localized. FurUROLOGY 77 (6), 2011

thermore, the PSA doubling times at the last follow-up visit for all patients were at rates associated with a low risk of clinically detectable metastatic disease at 5 years and a median survival of ⬎5 years,12 suggesting meaningful clinical benefit. The reported genitourinary and sexual side effects were minor and infrequent and no rectal toxicity occurred in the present series, in contrast to a study by MacDonald et al,13 who reported a 26% rate of chronic gastrointestinal toxicity and 24% chronic genitourinary toxicity after salvage external beam radiotherapy in 34 patients treated for similar palpable local recurrences.

CONCLUSIONS Our initial experience with the use of salvage brachytherapy in 5 patients with biopsy-proven local recurrences has demonstrated its technical feasibility and potential as an alternative to external beam radiotherapy for local control of recurrence in the prostatic fossa in selected patients after radical prostatectomy. The near absence of gastrointestinal and genitourinary toxicity compares favorably with the toxicity rates generally seen after salvage external beam radiotherapy, with additional advantages of lower cost and patient convenience. References 1. Nag S, Beyer D, Friedland J, et al. American Brachytherapy Society (ABS) recommendations for transperineal placement brachytherapy of prostate cancer. Int J Radiat Oncol Biol Phys. 1999;44:789-799. 2. Leibel TL, Phillips SA. Cancer of the Prostate. In: Phillips SA, Leibel TL, eds. Textbook of Radiation Oncology, 2nd ed. Philadelphia: Saunders Elsevier; 2004:959-1017.

UROLOGY 77 (6), 2011

3. Catalona WJ, Han M. Definitive therapy for localized prostate cancer—an overview. In: Wein AJ, Kavoussi LR, Peters CA, et al, eds. Campbell-Walsh Urology, 9th ed. Philadelphia: Saunders Elsevier; 2007. 4. Eastham J, Scardino P. Radical prostatectomy. In: Walsh PC, Retik AB, Vaughan E, et al, eds. Campbell’s Urology, 8th ed. Philadelphia: Saunders Elsevier; 2002:3080-3106. 5. D’Amico A, Crook J, Beard CJ, et al. Radiation therapy for prostate cancer. In: Walsh PC, Retik AB, Vaughan E, et al, eds. Campbell’s Urology, 8th ed. Philadelphia: Saunders Elsevier; 2002:3147-3170. 6. Green H, Pakenham K, Headley B, et al. Quality of life compared during pharmacological treatments and clinical monitoring for non-localized prostate cancer: a randomized controlled trial. BJU Int. 2004;93:975-979. 7. Smith MR. Changes in fat and lean body mass during androgendeprivation therapy for prostate cancer. Urology. 2004;63:742-745. 8. Potters L, Morgenstern C, Calugaru E. 12-Year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer. J Urol. 2005;173:1562-1566. 9. Vigneri P, Herati AS, Potters L. The second decade of prostate brachytherapy: evidence and cost based outcomes. Urol Oncol Semin Orig Investig. 2010;28:86-90. 10. Nag S, Beyer D, Friedland J, et al. American Brachytherapy Society (ABS) recommendations for transperineal placement brachytherapy of prostate cancer. Int J Radiat Oncol Biol Phys. 1999;44:789799. 11. Nag S, Bice W, DeWyngaert JK, et al. The American Brachytherapy Society recommendations for permanent prostate brachytherapy postimplant dosimetric analysis. Int J Radiat Oncol Biol Phys. 2000;46:221-230. 12. Lee A, D’Amico A. Utility of prostate-specific antigen kinetics in addition to clinical factors in the selection of patients for salvage local therapy. J Clin Oncol. 2005;23):8192-8197. 13. MacDonald OK, Schild SE, Vora SA, et al. Salvage radiotherapy for palpable, locally recurrent prostate cancer after radical prostatectomy. Int J Radiat Oncol Biol Phys. 2004;58:1530-1535.

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