Long-term clinical outcomes of 538 prostate carcinoma patients treated with combination high-dose-rate brachytherapy and external beam radiotherapy
- 4 Downloads
We report on the long-term clinical outcomes of clinically localized prostate carcinoma (PCa) patients treated with external beam radiotherapy (EBRT) in combination with high-dose-rate brachytherapy boost (HDR-B).
Material and methods
Between 2002 and 2015, 538 prostate carcinoma patients underwent combined HDR-B (Ir-192) of 16 Gy over 4 fractions and EBRT of 59.4 Gy over 33 fractions. Patients were segregated into risk groups according to the NCCN guidelines. The Cox proportional hazards model was used to elicit risk factors for decreased biochemical relapse-free survival (bRFS), distant metastasis-free survival (dMFS), and overall survival (OS). Patients were graded by a board of radiation oncologists for gastrointestinal (GI) and genitourinary (GU) adverse events due to radiation using CTCAE v4.03 guidelines at follow-up.
The mean follow-up was 49 months (range 6–145 months). Five-year bRFS for low-, intermediate-, and high-risk patients were 96.7%, 93.0%, and 78.5%, respectively. Five-year dMFS for low-, intermediate-, and high-risk patients were 100%, 96.4%, and 80.7%, respectively. Five-year OS rates for low-, intermediate-, and high-risk patients were 98.6%, 97.5%, and 94.7%, respectively. Five-year incidence of late grade 2 and 3 GI toxicities were 6.3% and 0.7%, respectively, and the five-year incidence of late grade 2 and 3 GU toxicities were 11.7% and 1.3%, respectively. Multivariate analysis revealed a higher Gleason score, initial pre-treatment PSA, and no hormonal therapy use as predictive for decreased biochemical control.
Combined HDR-B/EBRT for the treatment of clinically localized prostate cancer provides superb clinical outcomes with excellent 5-year bRFS, dMFS, OS, and late GI/GU toxicity rates.
KeywordsProstate cancer HDR brachytherapy Toxicity IMRT EBRT
(i) Conception and design: BML, KT; (ii) administrative support: KT; (iii) provision of study materials or patients: JY, RT, RB, MG, AW, CP, SC, KT; (iv) collection and assembly of data: BML, NM; (v) statistical analysis and interpretation: BML; (vi) manuscript writing—original draft: BML; (vii) final approval of manuscript: all authors.
A portion of the study was funded by the Medici Foundation (non-profit organization).
Compliance with ethical standards
Conflicts of interest
The authors declare they have no conflicts of interest.
Research involving human participants
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 6.Zietman AL, Bae K, Slater JD, Shipley WU, Efstathiou JA, Coen JJ, Bush DA, Lunt M, Spiegel DY, Skowronski R, Jabola BR, Rossi CJ (2010) 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 28(7):1106–1111PubMedPubMedCentralCrossRefGoogle Scholar
- 7.Zelefsky MJ, Pei X, Chou JF, Schechter M, Kollmeier M, Cox B, Yamada Y, Fidaleo A, Sperling D, Happersett L, Zhang Z (2011) Dose escalation for prostate cancer radiotherapy: predictors of long-term biochemical tumor control and distant metastases-free survival outcomes. Eur Urol 60(6):1133–1139PubMedCrossRefGoogle Scholar
- 15.Donovan JL, Hamdy FC, Lane JA, Mason M, Metcalfe C, Walsh E, Blazeby JM, Peters TJ, Holding P, Bonnington S, Lennon T, Bradshaw L, Cooper D, Herbert P, Howson J, Jones A, Lyons N, Salter E, Thompson P, Tidball S, Blaikie J, Gray C, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Kockelbergh R, Kynaston H, Paul A, Powell P, Prescott S, Rosario DJ, Rowe E, Davis M, Turner EL, Martin RM, Neal DE, ProtecT Study Group* (2016) Patient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer. N Engl J Med 375(15):1425–1437PubMedPubMedCentralCrossRefGoogle Scholar
- 17.Sathya JR, Davis IR, Julian JA, Guo Q, Daya D, Dayes IS, Lukka HR, Levine M (2005) Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate. J Clin Oncol 23(6):1192–1199PubMedCrossRefGoogle Scholar
- 20.Hsu IC, Bae K, Shinohara K, Pouliot J, Purdy J, Ibbott G, Speight J, Vigneault E, Ivker R, Sandler H (2010) Phase II trial of combined high-dose-rate brachytherapy and external beam radiotherapy for adenocarcinoma of the prostate: preliminary results of RTOG 0321. Int J Radiat Oncol Biol Phys 78(3):751–758PubMedPubMedCentralCrossRefGoogle Scholar
- 21.Morris WJ et al (2017) 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 98(2):275–285PubMedCrossRefGoogle Scholar
- 22.Rodda S, Tyldesley S, Morris WJ, Keyes M, Halperin R, Pai H, McKenzie M, Duncan G, Morton G, Hamm J, Murray N (2017) ASCENDE-RT: an analysis of treatment-related morbidity for a randomized trial comparing a low-dose-rate brachytherapy boost with a dose-escalated external beam boost for high- and intermediate-risk prostate cancer. Int J Radiat Oncol Biol Phys 98(2):286–295PubMedCrossRefGoogle Scholar
- 24.Yeh J, Lehrich B, Mesa A, Tran C, Barnes L, Long C, Yoshida J, Torrey R, Gazzaniga M, Albert S, Weinberg A, Alavi A, Baghdassarian R, Chalfin S, Ravera J, Tokita K (2017) Three-year outcomes of 324 prostate carcinoma patients treated with combination high-dose-rate brachytherapy and intensity modulated radiation therapy. Transl Cancer Res 6(2):269–274CrossRefGoogle Scholar
- 25.Mohler JL, Armstrong AJ, Bahnson RR, D’Amico AV, Davis BJ, Eastham JA, Enke CA, Farrington TA, Higano CS, Horwitz EM, Hurwitz M, Kane CJ, Kawachi MH, Kuettel M, Lee RJ, Meeks JJ, Penson DF, Plimack ER, Pow-Sang JM, Raben D, Richey S, Roach M III, Rosenfeld S, Schaeffer E, Skolarus TA, Small EJ, Sonpavde G, Srinivas S, Strope SA, Tward J, Shead DA, Freedman-Cass DA (2016) Prostate Cancer, version 1.2016. J Natl Compr Cancer Netw 14(1):19–30CrossRefGoogle Scholar
- 26.Yeh J, Lehrich B, Tran C, Mesa A, Baghdassarian R, Yoshida J, Torrey R, Gazzaniga M, Weinberg A, Chalfin S, Ravera J, Tokita K (2016) Polyethylene glycol hydrogel rectal spacer implantation in patients with prostate cancer undergoing combination high-dose-rate brachytherapy and external beam radiotherapy. Brachytherapy 15(3):283–287PubMedCrossRefGoogle Scholar
- 29.Roach M 3rd et al (2006) Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 65(4):965–974PubMedPubMedCentralCrossRefGoogle Scholar
- 33.Zelefsky MJ, Yamada Y, Fuks Z, Zhang Z, Hunt M, Cahlon O, Park J, Shippy A (2008) Long-term results of conformal radiotherapy for prostate cancer: impact of dose escalation on biochemical tumor control and distant metastases-free survival outcomes. Int J Radiat Oncol Biol Phys 71(4):1028–1033PubMedCrossRefGoogle Scholar
- 35.Dearnaley DP, Sydes MR, Graham JD, Aird EG, Bottomley D, Cowan RA, Huddart RA, Jose CC, Matthews JH, Millar J, Moore AR, Morgan RC, Russell JM, Scrase CD, Stephens RJ, Syndikus I, Parmar MK, RT01 collaborators (2007) Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncol 8(6):475–487PubMedCrossRefGoogle Scholar
- 40.Dayes IS, Parpia S, Gilbert J, Julian JA, Davis IR, Levine MN, Sathya J (2017) Long-term results of a randomized trial comparing iridium implant plus external beam radiation therapy with external beam radiation therapy alone in node-negative locally advanced cancer of the prostate. Int J Radiat Oncol Biol Phys 99(1):90–93PubMedCrossRefGoogle Scholar
- 43.Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D, Graham J, Kirkbride P, Logue J, Malik Z, Money-Kyrle J, O’Sullivan JM, Panades M, Parker C, Patterson H, Scrase C, Staffurth J, Stockdale A, Tremlett J, Bidmead M, Mayles H, Naismith O, South C, Gao A, Cruickshank C, Hassan S, Pugh J, Griffin C, Hall E, CHHiP Investigators (2016) 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 17(8):1047–1060PubMedPubMedCentralCrossRefGoogle Scholar
- 44.Galalae RM, Martinez A, Mate T, Mitchell C, Edmundson G, Nuernberg N, Eulau S, Gustafson G, Gribble M, Kovács G (2004) Long-term outcome by risk factors using conformal high-dose-rate brachytherapy (HDR-BT) boost with or without neoadjuvant androgen suppression for localized prostate cancer. Int J Radiat Oncol Biol Phys 58(4):1048–1055PubMedCrossRefGoogle Scholar
- 56.Ghadjar P, Thalmann GN (2012) Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU Int 110(10):E431–E432 author reply E432PubMedCrossRefGoogle Scholar
- 60.King MT, Yang DD, Muralidhar V, Mahal B, Butler S, Devlin PM, Lee LJ, Mouw KW, Martin NM, D’Amico AV, Nguyen PL, Orio PF III (2019) A comparative analysis of overall survival between high-dose-rate and low-dose-rate brachytherapy boosts for unfavorable-risk prostate cancer. Brachytherapy 18:186–191PubMedCrossRefGoogle Scholar