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High-dose intensity-modulated radiation therapy as primary treatment of prostate cancer: genitourinary/gastrointestinal toxicity and outcomes, a single-institution experience

  • Beatrice Detti
  • Muhammed Baki
  • Carlotta Becherini
  • Calogero Saieva
  • Daniele Scartoni
  • Irene Giacomelli
  • Laura TrombettaEmail author
  • Cristina Muntoni
  • Emanuela Olmetto
  • Giulio Francolini
  • Ana Turkaj
  • Juliana Topulli
  • Cinzia Ciabatti
  • Giulio Carta
  • Linda Poggesi
  • Camilla Delli Paoli
  • Francesca Terziani
  • Roberta Grassi
  • Lorenzo Livi
RADIOTHERAPY
  • 21 Downloads

Abstract

Purpose

Prostatectomy, radiotherapy and watchful waiting are the main therapeutic options available for local stage of prostate cancer (PCa). We report our experience on 394 patients affected by prostate cancer primarily treated with high-dose, image-guided, IMRT, focusing on gastrointestinal, genitourinary toxicities and biochemical control.

Methods

From July 2003 to August 2014, 394 patients were treated with radical high-dose radiotherapy (HDRT) for prostate cancer; the mean total radiation dose was 79 Gy in standard fractions. Hormonal therapy (HT) was administered to 7.6% of low-risk patients, to 20.3% of intermediate-risk patients and to 72% of high-risk patients. Patients were evaluated for biochemical failure, local recurrence (LR) and metastases.

Results

Ninety-seven patients (26.65%) developed acute GU toxicity at the medium dose of 25.4 Gy, grade 1 (G1) or grade 2 (G2) in 94 cases. Only 16 patients (4.06%) reported chronic GU toxicity (G1 or G2), and one case developed G3 cystitis. No G3 GI acute and late toxicity were detected. Fifty-six (14.2%) patients experienced LR, 26 (6.6%) developed metastases and 70 patients (17.8%) were deceased. Gleason sum score > 7 was predictive for worse overall survival (GS = 7 was borderline) and for metastasis. No factors resulted predictive for local relapse. HT pre-RT had been demonstrated as a negative predictor for OS and DFS-DM.

Conclusions

Data confirm the safety of HDRT for PCa. Treatment was efficient with low toxicity profile. Moreover, continued technologic advancements, as image-guided radiotherapy, could lead to further reduction in toxicity, thus increasing the therapeutic index.

Keywords

Prostate cancer Intensity-modulated radiation therapy (IMRT) Genitourinary toxicity Gastrointestinal toxicity 

Notes

Compliance with ethical standards

Conflict of interest

We declare that the absence of conflict of interest and financial relationships relevant to the content of this article have been disclosed by all authors. Our original article and our experience were not funded by an agency with a proprietary or financial interest. We had full access to all data in this study, and we take complete responsibility for the integrity of the data and the accuracy of the data analysis.

Research involving human participants

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and its later amendments or comparable ethical standards. For our retrospective study, formal consent is not required.

Informed consent

All authors declare that informed consent was obtained from all individual participants included in the study and to have used adequate strategies for protecting anonymity. Therefore, all patients gave the permission for manuscript to be published and their personal identifiers have been removed so as not to be identified; all patients cannot be identified through the details of the story.

References

  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90.  https://doi.org/10.3322/caac.20107 CrossRefGoogle Scholar
  2. 2.
    Siegel R, Naishadham D, Jemal A (2013) Cancer statistics 2013. CA Cancer J Clin 63:11–30.  https://doi.org/10.3322/caac.21166 CrossRefGoogle Scholar
  3. 3.
    González-San Segundo C, Herranz-Amo F, Alvarez-González A, Cuesta-Álvaro P, Gómez-Espi M, Paños-Fagundo E et al (2011) Radical prostatectomy versus external-beam radiotherapy for localized prostate cancer: long-term effect on biochemical control-in search of the optimal treatment. Ann Surg Oncol 18(10):2980–2987CrossRefGoogle Scholar
  4. 4.
    Peeters ST, Heemsbergen WD, Koper PC, van Putten WL, Slot A, Dielwart MF et al (2006) 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 24(13):1990–1996CrossRefGoogle Scholar
  5. 5.
    Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR et al (2008) Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 70(1):67–74CrossRefGoogle Scholar
  6. 6.
    Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E et al (2002) Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys 53(5):1097–1105CrossRefGoogle Scholar
  7. 7.
    Zietman AL, DeSilvio ML, Slater JD, Rossi CJ Jr, Miller DW, Adams JA et al (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):1233–1239CrossRefGoogle Scholar
  8. 8.
    Dearnaley DP, Sydes MR, Graham JD, Aird EG, Bottomley D, Cowan RA et al (2007) Escalated- dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomized controlled trial. Lancet Oncol 8(6):475–487CrossRefGoogle Scholar
  9. 9.
    Nam RK, Cheung P, Herschorn S, Saskin R, Su J, Klotz LH et al (2014) Incidence of complications other than urinary incontinence or erectile dysfunction after radical prostatectomy or radiotherapy for prostate cancer: a population-based cohort study. Lancet Oncol 15(2):223–231.  https://doi.org/10.1016/S1470-2045(13)70606-5 CrossRefPubMedGoogle Scholar
  10. 10.
    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.  https://doi.org/10.1016/j.ijrobp.2008.10.091 CrossRefPubMedGoogle Scholar
  11. 11.
    Huang EH, Pollack A, Levy L, Starkschall G, Dong L, Rosen I et al (2002) Late rectal toxicity: dose-volume effects of conformal radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 54(5):1314–1321CrossRefGoogle Scholar
  12. 12.
    Chennupati SK, Pelizzari CA, Kunnavakkam R, Liauw SL (2014) Late toxicity and quality of life after definitive treatment of prostate cancer: redefining optimal rectal sparing constraints for intensity-modulated radiation therapy. Cancer Med 3(4):954–961.  https://doi.org/10.1002/cam4.261 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Becker-Schiebe M, Abaci A, Ahmad T, Hoffmann W (2016) Reducing radiation-associated toxicity using online image guidance (IGRT) in prostate cancer patients undergoing dose-escalated radiation therapy. Rep Pract Oncol Radiother 21(3):188–194CrossRefGoogle Scholar
  14. 14.
    Michalski JM, Yan Y, Watkins-Bruner D, Bosch WR, Winter K, Galvin JM et al (2013) Preliminary toxicity analysis of 3-dimensional conformal radiation therapy versus intensity modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group 0126 prostate cancer trial. Int J Radiat Oncol Biol Phys 87(5):932–938CrossRefGoogle Scholar
  15. 15.
    Di Franco R, Borzillo V, Ravo V, Ametrano G, Falivene S, Cammarota F (2017) Rectal/urinary toxicity after hypofractionated vs conventional radiotherapy in low/intermediate risk localized prostate cancer: systematic review and metaanalysis. Oncotarget 8(10):17383–17395.  https://doi.org/10.18632/oncotarget.14798 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Mullaney LM, O’Shea E, Dunne MT, Finn MA, Thirion PG, Cleary LA et al (2014) A randomized trial comparing bladder volume consistency during fractionated prostate radiation therapy. Pract Radiat Oncol 4(5):e203–e212CrossRefGoogle Scholar
  17. 17.
    Fonteyne V, Sadeghi S, Ost P, Vanpachtenbeke F, Vuye P, Lumen N et al (2015) Impact of changing rectal dose volume parameters over time on late rectal and urinary toxicity after high-dose intensity-modulated radiotherapy for prostate cancer: a 10-years single centre experience. Acta Oncol 54(6):854–861CrossRefGoogle Scholar
  18. 18.
    Marks LB, Yorke ED, Jackson A, Ten Haken RK, Constine LS, Eisbruch A et al (2010) Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys 76(3 Suppl):S10–S19.  https://doi.org/10.1016/j.ijrobp.2009.07.1754 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Mullaney LM, O’Shea E, Dunne MT, Finn MA, Thirion PG, Cleary LA et al (2014) A randomized trial comparing bladder volume consistency during fractionated prostate radiation therapy. Pract Radiat Oncol 4(5):203–212CrossRefGoogle Scholar
  20. 20.
    D’Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA et al (1998) Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 280(11):969–974CrossRefGoogle Scholar
  21. 21.
    Roach M 3rd, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH, Sandler H (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.  https://doi.org/10.1016/j.ijrobp.2006.04.029 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Shrader-Bogen CL et al (1997) Quality of life and treatment outcomes: prostate carcinoma patients’ perspectives after prostatectomy or radiation therapy. Cancer 79(10):1977–1986CrossRefGoogle Scholar
  23. 23.
    Tyson MD et al (2018) Effect of prostate cancer severity on functional outcomes after localized treatment: comparative effectiveness analysis of surgery and radiation study results. Eur Urol 74:26–33CrossRefGoogle Scholar
  24. 24.
    Wallis CJD, Glaser A, Hu JC, Huland H, Lawrentschuk N, Moon D, Murphy DG, Nguyen PL, Resnick MJ, Nam RK (2018) Survival and complications following surgery and radiation for localized prostate cancer: an international collaborative review. Eur Urol 73(1):11–20.  https://doi.org/10.1016/j.eururo.2017.05.055 CrossRefPubMedGoogle Scholar
  25. 25.
    Spratt DE, Pei X, Yamada J, Kollmeier MA, Cox B, Zelefsky MJ (2013) Long-term survival and toxicity in patients treated with high-dose intensity modulated radiation therapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 85(3):686–692CrossRefGoogle Scholar
  26. 26.
    Cahlon O, Zelefsky MJ, Shippy A, Chan H, Fuks Z, Yamada Y et al (2008) Ultra-high dose (86.4 Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes. Int J Radiat Oncol Biol Phys 71(2):330–337.  https://doi.org/10.1016/j.ijrobp.2007.10.004 CrossRefPubMedGoogle Scholar
  27. 27.
    Zelefsky MJ, Fuks Z, Hunt M, Lee HJ, Lombardi D, Ling CC et al (2001) High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer. J Urol 166(3):876–881CrossRefGoogle Scholar
  28. 28.
    Arcangeli G, Saracino B, Gomellini S, Petrongari MG, Arcangeli S, Sentinelli S et al (2010) A Prospective phase III randomized trial of hypofractionation versus conventional fractionation in patients with high-risk prostate cancer. Int J Radiat Oncol Biol Phys 78(1):11–18.  https://doi.org/10.1016/j.ijrobp.2009.07.1691 CrossRefPubMedGoogle Scholar
  29. 29.
    Zelefsky MJ, Kollmeier M, Cox B, Fidaleo A, Sperling D, Pei X et al (2012) Improved clinical outcomes with high-dose image guided radiotherapy compared with non-IGRT for the treatment of clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 84(1):125–129.  https://doi.org/10.1016/j.ijrobp.2011.11.047 CrossRefPubMedGoogle Scholar
  30. 30.
    Pollack A, Zagars GK, Starkschall G, Childress CH, Kopplin S, Boyer AL et al (1996) Conventional vs. conformal radiotherapy for prostate cancer: preliminary results of dosimetry and acute toxicity. Int J Radiat Oncol Biol Phys 34(3):555–564CrossRefGoogle Scholar
  31. 31.
    Koper PC, Jansen P, van Putten W, van Os M, Wijnmaalen AJ, Lebesque JV et al (2004) Gastro-intestinal and genito-urinary morbidity after 3D conformal radiotherapy of prostate cancer: observations of a randomized trial. Radiother Oncol 73(1):1–9CrossRefGoogle Scholar
  32. 32.
    Peeters ST, Hoogeman MS, Heemsbergen WD, Slot A, Tabak H, Koper PC et al (2005) Volume and hormonal effects for acute side effects of rectum and bladder during conformal radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 63(4):1142–1152CrossRefGoogle Scholar
  33. 33.
    Schultheiss TE, Lee WR, Hunt MA, Hanlon AL, Peter RS, Hanks GE (1997) Late GI and GU complications in the treatment of prostate cancer. Int J Radiat Oncol Biol Phys 37(1):3–11CrossRefGoogle Scholar
  34. 34.
    Zelefsky MJ, Leibel SA, Gaudin PB, Kutcher GJ, Fleshner NE, Venkatramen ES et al (1998) Dose escalation with three dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys 41:491–500CrossRefGoogle Scholar
  35. 35.
    Pollack A, Zagars GK, Smith LG, Lee JJ, von Eschenbach AC, Antolak JA et al (2000) Preliminary results of a randomized radiotherapy dose escalation study comparing 70 Gy to 78 Gy for prostate cancer. J Clin Oncol 18:3904–3911CrossRefGoogle Scholar
  36. 36.
    Vora SA, Wong WW, Schild SE, Ezzell GA, Andrews PE, Ferrigni RG et al (2013) Outcome and toxicity for patients treated with intensity modulated radiation therapy for localized prostate cancer. J Urol 190(2):521–526.  https://doi.org/10.1016/j.juro.2013.02.012 CrossRefPubMedGoogle Scholar
  37. 37.
    Fellin G, Rancati T, Fiorino C, Vavassori V, Antognoni P, Baccolini M et al (2014) Long term rectal function after high-dose prostate cancer radiotherapy: results from a prospective cohort study. Radiother Oncol 110(2):272–277CrossRefGoogle Scholar
  38. 38.
    Slagsvold JE, Viset T, Wibe A, Kaasa S, Widmark A, Lund JÅ (2016) Radiation therapy did not induce long-term changes in rectal mucosa: results from the randomized Scandinavian Prostate Cancer Group-7 Trial. Int J Radiat Oncol Biol Phys 95(4):1268–1272.  https://doi.org/10.1016/j.ijrobp.2016.02.054 CrossRefPubMedGoogle Scholar
  39. 39.
    Dréan G, Acosta O, Ospina JD, Fargeas A, Lafond C, Corrégé G et al (2016) Identification of a rectal subregion highly predictive of rectal bleeding in prostate cancer IMRT. Radiother Oncol 119(3):388–397.  https://doi.org/10.1016/j.radonc.2016.04.023 CrossRefPubMedGoogle Scholar
  40. 40.
    Tomita N, Soga N, Ogura Y, Hayashi N, Kageyama T, Ito M et al (2016) High-dose radiotherapy with helical tomotherapy and long-term androgen deprivation therapy for prostate cancer: 5-year outcomes. J Cancer Res Clin Oncol 142(7):1609–1619.  https://doi.org/10.1007/s00432-016-2173-9 CrossRefPubMedGoogle Scholar
  41. 41.
    Taguchi S, Fukuhara H, Shiraishi K, Nakagawa K, Morikawa T, Kakutani S et al (2015) Radical prostatectomy versus external beam radiotherapy for cT1-4N0M0 prostate cancer: comparison of patient outcomes including mortality. PLoS ONE 10(10):e0141123.  https://doi.org/10.1371/journal.pone.0141123 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Kanakavelu N, Samuel EJ (2015) Assessment and evaluation of MV image guidance system performance in radiotherapy. Rep Pract Oncol Radiother 20(3):188–197.  https://doi.org/10.1016/j.rpor.2015.01.002 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Zapatero A, Guerrero A, Maldonado X, Alvarez A, Gonzalez San Segundo C, Cabeza Rodríguez MA, Macias V, Pedro Olive A, Casas F, Boladeras A, de Vidales CM, Vazquez de la Torre ML, Villà S, Perez de la Haza A, Calvo F (2015) High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol 16(3):320–327CrossRefGoogle Scholar
  44. 44.
    Helgstrand JT, Berg KD, Lippert S, Brasso K, Røder MA (2016) Systematic review: does endocrine therapy prolong survival in patients with prostate cancer? Scand J Urol. 50(3):135–143CrossRefGoogle Scholar
  45. 45.
    Gunner C, Gulamhusein A, Rosario D (2016) The modern role of androgen deprivation therapy in the management of localised and locally advanced prostate cancer. J ClinUrol 9(2 Suppl):24–29Google Scholar

Copyright information

© Italian Society of Medical Radiology 2019

Authors and Affiliations

  • Beatrice Detti
    • 1
  • Muhammed Baki
    • 1
  • Carlotta Becherini
    • 1
  • Calogero Saieva
    • 2
  • Daniele Scartoni
    • 1
  • Irene Giacomelli
    • 1
  • Laura Trombetta
    • 1
    Email author return OK on get
  • Cristina Muntoni
    • 1
  • Emanuela Olmetto
    • 1
  • Giulio Francolini
    • 1
  • Ana Turkaj
    • 1
  • Juliana Topulli
    • 1
  • Cinzia Ciabatti
    • 1
  • Giulio Carta
    • 1
  • Linda Poggesi
    • 1
  • Camilla Delli Paoli
    • 1
  • Francesca Terziani
    • 1
  • Roberta Grassi
    • 1
  • Lorenzo Livi
    • 1
  1. 1.Department of Radiation OncologyUniversity of FlorenceFlorenceItaly
  2. 2.Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO)University of FlorenceFlorenceItaly

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