A Prospective Phase 2 Trial of Transperineal Ultrasound-Guided Brachytherapy for Locally Recurrent Prostate Cancer After External Beam Radiation Therapy (NRG Oncology/RTOG-0526)

Juanita M Crook, Peixin Zhang, Thomas M Pisansky, Edouard J Trabulsi, Mahul B Amin, William Bice, Gerard Morton, Nadeem Pervez, Eric Vigneault, Charles Catton, Jeff Michalski, Mack Roach 3rd, David Beyer, Ashesh Jani, Eric Horwitz, Viroon Donavanik, Howard Sandler, Juanita M Crook, Peixin Zhang, Thomas M Pisansky, Edouard J Trabulsi, Mahul B Amin, William Bice, Gerard Morton, Nadeem Pervez, Eric Vigneault, Charles Catton, Jeff Michalski, Mack Roach 3rd, David Beyer, Ashesh Jani, Eric Horwitz, Viroon Donavanik, Howard Sandler

Abstract

Purpose: Only retrospective data are available for low-dose-rate (LDR) salvage prostate brachytherapy for local recurrence after external beam radiation therapy (EBRT). The primary objective of this prospective phase 2 trial (NCT00450411) was to evaluate late gastrointestinal and genitourinary adverse events (AEs) after salvage LDR brachytherapy.

Methods and materials: Eligible patients had low- or intermediate-risk prostate cancer before EBRT and biopsy-proven recurrence >30 months after EBRT, with prostate-specific antigen levels <10 ng/mL and no regional/distant disease. The primary endpoint was grade 3 or higher late treatment-related gastrointestinal or genitourinary AEs occurring 9 to 24 months after brachytherapy. These AEs were projected to be ≤10%, with ≥20% considered unacceptable. All events were graded with National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Multivariate analyses investigated associations of pretreatment or treatment variables with AEs.

Results: One hundred patients from 20 centers were registered from May 2007 to January 2014. The 92 analyzable patients had a median follow-up of 54 months (range, 4-97) and a median age of 70 years (interquartile range [IQR], 65-74). The initial Gleason score was 7 in 48% of patients. The median dose of EBRT was 74 Gy (IQR, 70-76) at a median interval of 85 months previously (IQR, 60-119). Only 16% had androgen deprivation at study entry. Twelve patients (14%) had late grade 3 gastrointestinal/genitourinary AEs, with no treatment-related grade 4 or 5 AEs. No pretreatment variable predicted late AEs, including prior EBRT dose and elapsed interval. Higher V100 (percentage of prostate enclosed by prescription isodose) predicted both occurrence of late AEs (odds ratio, 1.24; 95% confidence interval, 1.02-1.52; P = .03) and earlier time to first occurrence (hazard ratio, 1.18; 95% CI, 1.03-1.34; P = .02).

Conclusions: This prospective multicenter trial reports outcomes of salvage LDR brachytherapy for post-EBRT recurrence. The rate of late grade 3 AEs did not exceed the unacceptable threshold. The only factor predictive of late AEs was implant dosimetry reflected by V100. Efficacy outcomes will be reported at a minimum of 5-year follow-up.

Conflict of interest statement

Conflict of interest statement:

Drs. Amin, Beyer, Bice, Crook, Donavanik, Horwitz, Jani, Michalski, Morton, Pisansky, Roach, Trabulski, Vigneault, and Zhang have nothing to disclose. Dr. Catton reports grants from NRG, during the conduct of the study; personal fees from Sanofi Corp, personal fees from Abbvie Corp, personal fees from Bayer Corp, personal fees from Janssen Corp. Dr. Pervez reports grants from Standard Grant per patient from NRG. Dr. Sandler reports grants from ACR-NRG Oncology, during the conduct of the study; personal fees from Ferring, personal fees from Blue Earth Diagnostics, personal fees from Janssen, personal fees from Caribou Publishing.

Copyright © 2018 Elsevier Inc. All rights reserved.

References

    1. Nichol A, Chung P, Lockwood G, Rosewall T, Divanbiegi L, Sweet J, et al. A phase II study of localized prostate cancer treated to 75.6 Gy with 3D conformal radiotherapy. Radiother Oncol 2005. July;76(1):11–17.
    1. Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, et al. Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 2008. January 1;70(1):67–74.
    1. Michalski J, Winter K, Roach M, Markoe A, Sandler HM, Ryu J, et al. Clinical outcome of patients treated with 3D conformal radiation therapy (3D-CRT) for prostate cancer on RTOG 9406. Int J Radiat Oncol Biol Phys 2012. July 1;83(3):e363–70.
    1. Beckendorf V, Guerif S, Le Prise E, Cosset JM, Bougnoux A, Chauvet B, et al. 70 Gy versus 80 Gy in localized prostate cancer: 5-year results of GETUG 06 randomized trial. Int J Radiat Oncol Biol Phys 2011. July 15;80(4):1056–1063.
    1. Catton CN, Lukka H, Gu CS, Martin JM, Supiot S, Chung PWM, et al. Randomized Trial of a Hypofractionated Radiation Regimen for the Treatment of Localized Prostate Cancer. J Clin Oncol 2017. June 10;35(17):1884–1890.
    1. Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D, et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol 2016. August;17(8):1047–1060.
    1. Lee WR, Dignam JJ, Amin MB, Bruner DW, Low D, Swanson GP, et al. Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer. J Clin Oncol 2016. July 10;34(20):2325–2332.
    1. Morris WJ, Tyldesley S, Rodda S, Halperin R, Pai H, McKenzie M, et al. Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer. Int J Radiat Oncol Biol Phys 2017. June 1;98(2):275–285.
    1. Pucar D, Hricak H, Shukla-Dave A, Kuroiwa K, Drobnjak M, Eastham J, et al. Clinically significant prostate cancer local recurrence after radiation therapy occurs at the site of primary tumor: magnetic resonance imaging and step-section pathology evidence. Int J Radiat Oncol Biol Phys 2007. September 1;69(1):62–69.
    1. Tran H, Kwok J, Pickles T, Tyldesley S, Black PC. Underutilization of local salvage therapy after radiation therapy for prostate cancer. Urol Oncol 2014. July;32(5):701–706.
    1. Coen JJ, Zietman AL, Thakral H, Shipley WU. Radical radiation for localized prostate cancer: local persistence of disease results in a late wave of metastases. J Clin Oncol 2002. August 1;20(15):3199–3205.
    1. Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 2006. September 20;24(27):4448–56.
    1. Grado GL. Benefits of brachytherapy as salvage treatment for radiorecurrent localized prostate cancer. Urology 1999. August;54(2):204–207.
    1. Beyer DC. Permanent brachytherapy as salvage treatment for recurrent prostate cancer. Urology 1999. November;54(5):880–883.
    1. Fleming TR. One-sample multiple testing procedure for phase II clinical trials. Biometrics 1982. March;38(1):143–151.
    1. Zelefsky MJ, Reuter VE, Fuks Z, Scardino P, Shippy A. Influence of Local Tumor Control on Distant Metastases and Cancer Related Mortality After External Beam Radiotherapy for Prostate Cancer. J Urol 2008. February 18.
    1. Fuks Z, Leibel SA, Wallner KE, Begg CB, Fair WR, Anderson LL, et al. The effect of local control on metastatic dissemination in carcinoma of the prostate: long-term results in patients treated with 125I implantation. Int J Radiat Oncol Biol Phys 1991. August;21(3):537–47.
    1. Peeters ST, Heemsbergen WD, Koper PC, van Putten WL, Slot A, Dielwart MF, et al. Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol 2006. May 1;24(13):1990–1996.
    1. Dearnaley DP, Sydes MR, Graham JD, Aird EG, Bottomley D, Cowan RA, et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncol 2007. June;8(6):475–487.
    1. Zietman AL, Bae K, Slater JD, Shipley WU, Efstathiou JA, Coen JJ, et al. Randomized trial comparing conventional-dose with high-dose conformal radiation therapy in early-stage adenocarcinoma of the prostate: long-term results from proton radiation oncology group/american college of radiology 95-09. J Clin Oncol 2010. March 1;28(7):1106–1111.
    1. Arrayeh E, Westphalen AC, Kurhanewicz J, Roach M, 3rd, Jung AJ, Carroll PR, et al. Does local recurrence of prostate cancer after radiation therapy occur at the site of primary tumor? Results of a longitudinal MRI and MRSI study. Int J Radiat Oncol Biol Phys 2012. April 1;82(5):e787–93.
    1. Viani GA, Pellizzon AC, Guimaraes FS, Jacinto AA, dos Santos Novaes PE, Salvajoli JV. High dose rate and external beam radiotherapy in locally advanced prostate cancer. Am J Clin Oncol 2009. April;32(2):187–190.
    1. Duchesne GM, Woo HH, King M, Bowe SJ, Stockler MR, Ames A, et al. Health-related quality of life for immediate versus delayed androgen-deprivation therapy in patients with asymptomatic, non-curable prostate cancer (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial. Lancet Oncol 2017. September;18(9):1192–1201.
    1. Crook JM, O'Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM, et al. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med 2012. September 6;367(10):895–903.
    1. Harris WP, Mostaghel EA, Nelson PS, Montgomery B, Medscape. Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion. Nat Clin Pract Urol 2009. February;6(2):76–85.

    1. Redbook. 2016.

    1. Dragomir A, Dinea D, Vanhuyse M, Cury FL, Aprikian AG. Drug costs in the management of metastatic castration-resistant prostate cancer in Canada. BMC Health Serv Res 2014. June 13;14:252-6963-14-252.
    1. Aaronson DS, Yamasaki I, Gottschalk A, Speight J, Hsu IC, Pickett B, et al. Salvage permanent perineal radioactive-seed implantation for treating recurrence of localized prostate adenocarcinoma after external beam radiotherapy. BJU Int 2009. September;104(5):600–604.
    1. Wong WW, Buskirk SJ, Schild SE, Prussak KA, Davis BJ. Combined prostate brachytherapy and short-term androgen deprivation therapy as salvage therapy for locally recurrent prostate cancer after external beam irradiation. J Urol 2006. November;176(5):2020–2024.
    1. Nguyen PL, Chen RC, Clark JA, Cormack RA, Loffredo M, McMahon E, et al. Patient-reported quality of life after salvage brachytherapy for radio-recurrent prostate cancer: A prospective Phase II study. Brachytherapy 2009. Oct-Dec;8(4):345–352.
    1. Burri RJ, Stone NN, Unger P, Stock RG. Long-term outcome and toxicity of salvage brachytherapy for local failure after initial radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 2010. August 1;77(5):1338–1344.
    1. Crook JM, Bahadur YA, Robertson SJ, Perry GA, Esche BA. Evaluation of radiation effect, tumor differentiation, and prostate specific antigen staining in sequential prostate biopsies after external beam radiotherapy for patients with prostate carcinoma. Cancer 1997. January 1;79(1):81–89.
    1. Shilkrut M, McLaughlin PW, Merrick GS, Vainshtein JM, Feng FY, Hamstra DA. Interval to biochemical failure predicts clinical outcomes in patients with high-risk prostate cancer treated by combined-modality radiation therapy. Int J Radiat Oncol Biol Phys 2013. July 15;86(4):721–728.
    1. Buyyounouski MK, Hanlon AL, Horwitz EM, Pollack A. Interval to biochemical failure highly prognostic for distant metastasis and prostate cancer-specific mortality after radiotherapy. Int J Radiat Oncol Biol Phys 2008. January 1;70(1):59–66.
    1. Nguyen PL, D’Amico AV, Lee AK, Suh WW. Patient selection, cancer control, and complications after salvage local therapy for postradiation prostate-specific antigen failure: a systematic review of the literature. Cancer 2007. October 1;110(7):1417–1428.
    1. Zagars GK, Pollack A. Kinetics of serum prostate-specific antigen after external beam radiation for clinically localized prostate cancer. Radiother Oncol 1997. September;44(3):213–221.
    1. D'Amico AV, Moul J, Carroll PR, Sun L, Lubeck D, Chen MH. Surrogate end point for prostate cancer specific mortality in patients with nonmetastatic hormone refractory prostate cancer. J Urol 2005. May;173(5):1572–1576.
    1. Martinez AA, Gonzalez J, Ye H, Ghilezan M, Shetty S, Kernen K, et al. Dose escalation improves cancer-related events at 10 years for intermediate- and high-risk prostate cancer patients treated with hypofractionated high-dose-rate boost and external beam radiotherapy. Int J Radiat Oncol Biol Phys 2011. February 1;79(2):363–370.
    1. Stock RG, Ho A, Cesaretti JA, Stone NN. Changing the patterns of failure for high-risk prostate cancer patients by optimizing local control. Int J Radiat Oncol Biol Phys 2006. October 1;66(2):389–94.
    1. Rose JN, Crook JM, Pickles T, Keyes M, Morris WJ. Salvage low-dose-rate permanent seed brachytherapy for locally recurrent prostate cancer: Association between dose and late toxicity. Brachytherapy 2015. May-Jun;14(3):342–349.
    1. Emmett L, van Leeuwen PJ, Nandurkar R, Scheltema MJ, Cusick T, Hruby G, et al. Treatment Outcomes from (68)Ga-PSMA PET/CT-Informed Salvage Radiation Treatment in Men with Rising PSA After Radical Prostatectomy: Prognostic Value of a Negative PSMA PET. J Nucl Med 2017. December;58(12):1972–1976.
    1. Morigi JJ, Stricker PD, van Leeuwen PJ, Tang R, Ho B, Nguyen Q, et al. Prospective Comparison of 18F-Fluoromethylcholine Versus 68Ga-PSMA PET/CT in Prostate Cancer Patients Who Have Rising PSA After Curative Treatment and Are Being Considered for Targeted Therapy. J Nucl Med 2015. August;56(8):1185–1190.
    1. Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, et al. Diagnostic performance of (68)Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging 2017. August;44(8):1258–1268.
    1. Moman MR, van der Poel HG, Battermann JJ, Moerland MA, van Vulpen M. Treatment outcome and toxicity after salvage 125-I implantation for prostate cancer recurrences after primary 125-I implantation and external beam radiotherapy. Brachytherapy 2010. Apr-Jun;9(2):119–125.
    1. Alemozaffar M, Regan MM, Cooperberg MR, Wei JT, Michalski JM, Sandler HM, et al. Prediction of erectile function following treatment for prostate cancer. JAMA 2011. September 21;306(11):1205–1214.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner