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Long-term clinical outcomes of 538 prostate carcinoma patients treated with combination high-dose-rate brachytherapy and external beam radiotherapy

  • Original Research
  • Published:
Journal of Radiation Oncology

Abstract

Purpose

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.

Results

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.

Conclusion

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.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424

    Article  PubMed  Google Scholar 

  2. Breslow N, Chan CW, Dhom G, Drury RAB, Franks LM, Gellei B, Lee YS, Lundberg S, Sparke B, Sternbya NH, Tulinius H (1977) Latent carcinoma of prostate at autopsy in seven areas. The International Agency for Research on Cancer, Lyons, France. Int J Cancer 20(5):680–688

    Article  CAS  PubMed  Google Scholar 

  3. Zelefsky MJ, Chan H, Hunt M, Yamada Y, Shippy AM, Amols H (2006) Long-term outcome of high dose intensity modulated radiation therapy for patients with clinically localized prostate cancer. J Urol 176(4 Pt 1):1415–1419

    Article  PubMed  Google Scholar 

  4. Zelefsky MJ et al (2001) High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer. J Urol 166(3):876–881

    Article  CAS  PubMed  Google Scholar 

  5. Zietman AL, DeSilvio ML, Slater JD, Rossi CJ, Miller DW, Adams JA, Shipley WU (2005) Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA 294(10):1233–1239

    Article  CAS  PubMed  Google Scholar 

  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):1106–1111

    Article  PubMed  PubMed Central  Google 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):1133–1139

    Article  PubMed  Google Scholar 

  8. Pugh TJ, Nguyen BN, Kanke JE, Johnson JL, Hoffman KE (2013) Radiation therapy modalities in prostate cancer. J Natl Compr Cancer Netw 11(4):414–421

    Article  CAS  Google Scholar 

  9. D’Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW (2008) Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA 299(3):289–295

    Article  PubMed  Google Scholar 

  10. Spratt DE et al (2014) Comparison of high-dose (86.4 Gy) IMRT vs combined brachytherapy plus IMRT for intermediate-risk prostate cancer. BJU Int 114(3):360–367

    PubMed  Google Scholar 

  11. Bowes D, Crook J (2011) A critical analysis of the long-term impact of brachytherapy for prostate cancer: a review of the recent literature. Curr Opin Urol 21(3):219–224

    Article  PubMed  Google Scholar 

  12. Fowler FJ Jr et al (2000) Comparison of recommendations by urologists and radiation oncologists for treatment of clinically localized prostate cancer. JAMA 283(24):3217–3222

    Article  PubMed  Google Scholar 

  13. Cooperberg MR, Carroll PR (2015) Trends in management for patients with localized prostate cancer, 1990-2013. JAMA 314(1):80–82

    Article  CAS  PubMed  Google Scholar 

  14. Resnick MJ, Koyama T, Fan KH, Albertsen PC, Goodman M, Hamilton AS, Hoffman RM, Potosky AL, Stanford JL, Stroup AM, van Horn RL, Penson DF (2013) Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med 368(5):436–445

    Article  CAS  PubMed  PubMed Central  Google 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):1425–1437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Huang GJ, Sadetsky N, Penson DF (2010) Health related quality of life for men treated for localized prostate cancer with long-term followup. J Urol 183(6):2206–2212

    Article  PubMed  PubMed Central  Google 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):1192–1199

    Article  PubMed  Google Scholar 

  18. Hoskin PJ, Motohashi K, Bownes P, Bryant L, Ostler P (2007) High dose rate brachytherapy in combination with external beam radiotherapy in the radical treatment of prostate cancer: initial results of a randomised phase three trial. Radiother Oncol 84(2):114–120

    Article  PubMed  Google Scholar 

  19. Hoskin PJ, Rojas AM, Bownes PJ, Lowe GJ, Ostler PJ, Bryant L (2012) Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer. Radiother Oncol 103(2):217–222

    Article  PubMed  Google 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):751–758

    Article  PubMed  PubMed Central  Google 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):275–285

    Article  PubMed  Google 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):286–295

    Article  PubMed  Google Scholar 

  23. Kee DLC, Gal J, Falk AT, Schiappa R, Chand ME, Gautier M, Doyen J, Hannoun-levi JM (2018) Brachytherapy versus external beam radiotherapy boost for prostate cancer: systematic review with meta-analysis of randomized trials. Cancer Treat Rev 70:265–271

    Article  PubMed  Google 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):269–274

    Article  Google 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):19–30

    Article  Google 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):283–287

    Article  PubMed  Google Scholar 

  27. Roberts, T. and M. Roach, 3rd, The evolving role of pelvic radiation therapy. Semin Radiat Oncol, 2003. 13(2): p. 109–120

  28. Fowler JF (2010) 21 years of biologically effective dose. Br J Radiol 83(991):554–568

    Article  CAS  PubMed  PubMed Central  Google 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):965–974

    Article  PubMed  Google Scholar 

  30. Zelefsky MJ, Fuks Z, Hunt M, Yamada Y, Marion C, Ling CC, Amols H, Venkatraman ES, Leibel SA (2002) High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients. Int J Radiat Oncol Biol Phys 53(5):1111–1116

    Article  PubMed  Google Scholar 

  31. Kuban DA, Levy LB, Cheung MR, Lee AK, Choi S, Frank S, Pollack A (2011) Long-term failure patterns and survival in a randomized dose-escalation trial for prostate cancer. Who dies of disease? Int J Radiat Oncol Biol Phys 79(5):1310–1317

    Article  PubMed  Google Scholar 

  32. Pollack A, Zagars GK, Smith LG, Lee JJ, von Eschenbach AC, Antolak JA, Starkschall G, Rosen I (2000) Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer. J Clin Oncol 18(23):3904–3911

    Article  CAS  PubMed  Google 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):1028–1033

    Article  PubMed  Google Scholar 

  34. Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, Lee AK, Pollack A (2008) Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 70(1):67–74

    Article  PubMed  Google 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):475–487

    Article  PubMed  Google Scholar 

  36. Al-Mamgani A et al (2008) Update of Dutch multicenter dose-escalation trial of radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 72(4):980–988

    Article  PubMed  Google Scholar 

  37. Viani GA, Stefano EJ, Afonso SL (2009) Higher-than-conventional radiation doses in localized prostate cancer treatment: a meta-analysis of randomized, controlled trials. Int J Radiat Oncol Biol Phys 74(5):1405–1418

    Article  PubMed  Google Scholar 

  38. Mendez LC, Morton GC (2018) High dose-rate brachytherapy in the treatment of prostate cancer. Transl Androl Urol 7(3):357–370

    Article  PubMed  PubMed Central  Google Scholar 

  39. Lyons JA, Kupelian PA, Mohan DS, Reddy CA, Klein EA (2000) Importance of high radiation doses (72 Gy or greater) in the treatment of stage T1-T3 adenocarcinoma of the prostate. Urology 55(1):85–90

    Article  CAS  PubMed  Google 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):90–93

    Article  PubMed  Google Scholar 

  41. Pollack A, Walker G, Horwitz EM, Price R, Feigenberg S, Konski AA, Stoyanova R, Movsas B, Greenberg RE, Uzzo RG, Ma C, Buyyounouski MK (2013) Randomized trial of hypofractionated external-beam radiotherapy for prostate cancer. J Clin Oncol 31(31):3860–3868

    Article  PubMed  PubMed Central  Google Scholar 

  42. Arcangeli S, Strigari L, Gomellini S, Saracino B, Petrongari MG, Pinnarò P, Pinzi V, Arcangeli G (2012) Updated results and patterns of failure in a randomized hypofractionation trial for high-risk prostate cancer. Int J Radiat Oncol Biol Phys 84(5):1172–1178

    Article  PubMed  Google 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):1047–1060

    Article  PubMed  PubMed Central  Google 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):1048–1055

    Article  PubMed  Google Scholar 

  45. Demanes DJ, Rodriguez RR, Schour L, Brandt D, Altieri G (2005) High-dose-rate intensity-modulated brachytherapy with external beam radiotherapy for prostate cancer: California endocurietherapy’s 10-year results. Int J Radiat Oncol Biol Phys 61(5):1306–1316

    Article  PubMed  Google Scholar 

  46. Kotecha R, Yamada Y, Pei X, Kollmeier MA, Cox B, Cohen G’N, Zaider M, Zelefsky MJ (2013) Clinical outcomes of high-dose-rate brachytherapy and external beam radiotherapy in the management of clinically localized prostate cancer. Brachytherapy 12(1):44–49

    Article  PubMed  Google Scholar 

  47. Martinez-Monge R et al (2012) External-beam radiation therapy and high-dose rate brachytherapy combined with long-term androgen deprivation therapy in high and very high prostate cancer: preliminary data on clinical outcome. Int J Radiat Oncol Biol Phys 82(3):e469–e476

    Article  PubMed  Google Scholar 

  48. Neviani CB, Miziara MA, de Andrade Carvalho H (2011) Results of high dose-rate brachytherapy boost before 2D or 3D external beam irradiation for prostate cancer. Radiother Oncol 98(2):169–174

    Article  PubMed  Google Scholar 

  49. Phan TP, Syed AMN, Puthawala A, Sharma A, Khan F (2007) High dose rate brachytherapy as a boost for the treatment of localized prostate cancer. J Urol 177(1):123–127; discussion 127

    Article  PubMed  Google Scholar 

  50. Eulau SM et al (2000) High dose rate 192Iridium brachytherapy in localized prostate cancer: results and toxicity with maximum follow-up of 10 years. Int J Radiat Oncol Biol Phys 48(3):149

    Article  Google Scholar 

  51. Yaxley JW, Lah K, Yaxley JP, Gardiner RA, Samaratunga H, MacKean J (2017) Long-term outcomes of high-dose-rate brachytherapy for intermediate- and high-risk prostate cancer with a median follow-up of 10 years. BJU Int 120(1):56–60

    Article  CAS  PubMed  Google Scholar 

  52. Khor R, Duchesne G, Tai KH, Foroudi F, Chander S, van Dyk S, Garth M, Williams S (2013) Direct 2-arm comparison shows benefit of high-dose-rate brachytherapy boost vs external beam radiation therapy alone for prostate cancer. Int J Radiat Oncol Biol Phys 85(3):679–685

    Article  PubMed  Google Scholar 

  53. Spratt DE et al (2017) American Brachytherapy Society Task Group Report: combination of brachytherapy and external beam radiation for high-risk prostate cancer. Brachytherapy 16(1):1–12

    Article  PubMed  Google Scholar 

  54. Stock RG, Yamalachi S, Hall SJ, Stone NN (2010) Impact of hormonal therapy on intermediate risk prostate cancer treated with combination brachytherapy and external beam irradiation. J Urol 183(2):546–550

    Article  CAS  PubMed  Google Scholar 

  55. Bittner N, Merrick GS, Galbreath RW, Butler WM, Adamovich E (2015) Treatment outcomes with permanent brachytherapy in high-risk prostate cancer patients stratified into prognostic categories. Brachytherapy 14(6):766–772

    Article  CAS  PubMed  Google 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 E432

    Article  PubMed  Google Scholar 

  57. Singhal S, Jamaluddin MF, Lee E, Sloboda RS, Parliament M, Usmani N (2017) Clinical factors and dosimetry associated with the development of prostate brachytherapy-related urethral strictures: a matched case-control study. Brachytherapy 16(4):797–805

    Article  PubMed  Google Scholar 

  58. Sullivan L, Williams SG, Tai KH, Foroudi F, Cleeve L, Duchesne GM (2009) Urethral stricture following high dose rate brachytherapy for prostate cancer. Radiother Oncol 91(2):232–236

    Article  PubMed  Google Scholar 

  59. King CR (2002) LDR vs. HDR brachytherapy for localized prostate cancer: the view from radiobiological models. Brachytherapy 1(4):219–226

    Article  PubMed  Google 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 18:186–191

    Article  PubMed  Google Scholar 

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Contributions

(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.

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A portion of the study was funded by the Medici Foundation (non-profit organization).

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Correspondence to Brandon M. Lehrich or Kenneth Tokita.

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Lehrich, B.M., Ravera, J., Mostaghni, N. et al. Long-term clinical outcomes of 538 prostate carcinoma patients treated with combination high-dose-rate brachytherapy and external beam radiotherapy. J Radiat Oncol 8, 311–321 (2019). https://doi.org/10.1007/s13566-019-00401-2

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