Skip to main content
SpringerLink
Log in

Moderate risk-adapted dose escalation with three-dimensional conformal radiotherapy of localized prostate cancer from 70 to 74 Gy

First report on 5-year morbidity and biochemical control from a prospective Austrian-German multicenter phase II trial

Dreidimensionale konformale risikoadaptierte Radiotherapie des lokalisierten Prostatakarzinoms mit moderater Dosiseskalation von 70 auf 74 Gy. 5-Jahres-Resultate der prospektiven österreichisch-deutschen Phase-II-Multicenterstudie

  • Original Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Purpose:

Evaluation of late side effects and biochemical control (bNED) 5 years after three-dimensional radiotherapy with moderate, risk-adapted dose escalation.

Patients and Methods:

From 03/1999 to 07/2002, 486 patients have been registered in the prospective Austrian-German multicenter phase II trial (AUGE). 399 (82%) localized prostate cancer patients (T1–3 Nx/N0 M0) were evaluated. The low- and intermediate-risk groups were treated with 70 Gy, the high-risk group with 74 Gy, respectively. Additional hormonal therapy (HT) was recommended for intermediate- and high-risk group patients. Late toxicity (EORTC/RTOG) and bNED (ASTRO and Phoenix) were prospectively assessed.

Results:

Median follow-up was 65 months. Distribution concerning risk groups (low-, intermediate-, high-risk group) showed 29%, 50% and 21% of patients, respectively. HT was given in 87% of patients. The 5-year actuarial rates of late side effects grade ≥ 2 for 70 Gy/74 Gy were 28%/30% (gastrointestinal; p = 0.73) and 19%/34% (urogenital; p = 0,06). The 5-year actuarial bNED rate stratified by risk groups (low-, intermediate-, high-risk group) was 74%, 66% and 50% (ASTRO), and 81%, 80% and 60% (Phoenix), respectively. Within multivariate analysis T-stage and initial prostate specific antigen were significant factors influencing bNED (ASTRO) whereas Gleason Score and duration of HT were not.

Conclusion:

Dose escalation within standard three-dimensional conformal radiotherapy (3D-CRT) up to a level of 74 Gy did not result in significantly increased gastrointestinal side effects, whereas urogenital side effects showed an increase close to significance. However, the total number of patients with severe toxicity was low. To achieve high tumor control rates with acceptable treatment-related morbidity, local doses of at least 74 Gy should be considered, in particular for intermediate- or high-risk patients applying 3D-CRT.

Ziel:

Bestimmung von Spätnebenwirkungen und biochemischer Kontrolle (bNED) nach risikoadaptierter Dosiseskalation im Rahmen einer prospektiven österreichisch-deutschen Phase-II-Multicenterstudie.

Patienten und Methodik:

Von 03/1999 bis 07/2002 wurden 486 Patienten mit Prostatakarzinom (T1–3 Nx/N0 M0) gemeldet, und 399 (82%) kamen zur Auswertung. Patienten der Niedrig- und Intermediärrisikogruppe wurden mit 70 Gy, die Hochrisikogruppe mit 74 Gy bestrahlt (Tabelle 1). Eine begleitende Hormontherapie wurde für Patienten der Intermediär- und Hochrisikogruppe empfohlen. Spätnebenwirkungen (EORTC/RTOG) und bNED (ASTRO/Phoenix) wurden ermittelt.

Ergebnisse:

Der mittlere Nachbeobachtungszeitraum betrug 65 Monate. Hinsichtlich der Risikogruppen (Niedrig-, Intermediär-, Hochrisikogruppe) fanden sich 29%, 50%, und 21% Patienten. Eine begleitende Hormontherapie erhielten 87% der Patienten. Detaillierte Patientendaten sind in Tabelle 2 aufgeführt. Die 5-Jahres-Raten an Spätnebenwirkungen Grad ≥ 2 für 70 Gy/74 Gy lagen bei 28%/30% (gastrointestinal; p = 0,73) und 19%/34% (urogenital; p = 0,06; Abbildungen 1 und 2). Die 5-Jahres-bNED-Raten entsprechend den Risikogruppen (Niedrig-, Intermediär-, Hochrisikogruppe) lagen bei 74%, 66% und 50% (ASTRO; Abbildung 3) bzw. 81%, 80% und 60% (Phoenix; Abbildung 4). In der multivariaten Analyse zeigten sich T-Stadium und initiales prostataspezifisches Antigen als signifikant bezüglich bNED (ASTRO) und Gleason-Score sowie die Dauer der Hormontherapie als nicht signifikant (Tabelle 4).

Schlussfolgerung:

Die Dosissteigerung auf 74 Gy führt zu keinen signifikant erhöhten Raten an gastrointestinalen Spätnebenwirkungen. Die Rate an urogenitalen Spätnebenwirkungen ist hingegen erhöht. Insgesamt finden sich jedoch nur wenige schwere Grad-3-Spätnebenwirkungen (Tabelle 3). Um respektable Tumorkontrollraten (Abbildung 5) zu erreichen, sollte, vor allem für Patienten der Intermediär- und Hochrisikogruppe, eine lokale Dosis von zumindest 74 Gy appliziert werden.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. American Society for Therapeutic Radiology and Oncology Consensus Panel. Consensus statement: guidelines for PSA following radiation therapy. Int J Radiat Oncol Biol Phys 1997;37:1035–41.

    Google Scholar 

  2. Cavey ML, Bayouth JE, Colman M, et al. IMRT to escalate the dose to the prostate while treating the pelvic nodes. Strahlenther Onkol 2005;181:431–41.

    Article  PubMed  Google Scholar 

  3. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995;31:1341–6.

    PubMed  CAS  Google Scholar 

  4. Dearnaley DP, Sydes MR, Graham JD, et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncol 2007;8:475–87.

    Article  PubMed  Google Scholar 

  5. De Meerleer G, Vakaet L, De Gersem W, et al. Direct segment aperture and weight optimization for intensity-modulated radiotherapy of prostate cancer. Strahlenther Onkol 2004;180:136–43.

    Article  PubMed  Google Scholar 

  6. Dobler B, Mai S, Ross C, et al. Evaluation of possible prostate displacement induced by pressure applied during transabdominal ultrasound image acquisition. Strahlenther Onkol 2006;182:240–6.

    Article  PubMed  Google Scholar 

  7. Eade TN, Hanlon AL, Horwitz EM, et al. What dose of external-beam radiation is high enough for prostate cancer? Int J Radiat Oncol Biol Phys 2007;68:682–9.

    PubMed  Google Scholar 

  8. Fiorino C, Fellin G, Rancati T, et al. Clinical and dosimetric predictors of late rectal syndrome after 3D-CRT for localized prostate cancer: preliminary results of a multicenter prospective study. Int J Radiat Oncol Biol Phys 2008;70:1130–7.

    PubMed  Google Scholar 

  9. Gershkevitsh E, Clark CH, Staffurth J, et al. Dose to bone marrow using IMRT techniques in prostate cancer patients. Strahlenther Onkol 2005;181:172–8.

    Article  PubMed  Google Scholar 

  10. Gerstner N, Wachter S, Dorner D, et al. Significance of a rectal balloon as internal immobilization device in conformal radiotherapy of prostatic carcinoma. Strahlenther Onkol 1999;175:232–8.

    Article  PubMed  CAS  Google Scholar 

  11. Grosu AL, Piert M, Weber WA, et al. Positron emission tomography for radiation treatment planning. Strahlenther Onkol 2005;181:483–99.

    Article  PubMed  Google Scholar 

  12. Guckenberger M, Flentje M. Intensity-modulated radiotherapy (IMRT) of localized prostate cancer. A review and future perspectives. Strahlenther Onkol 2007;183:57–62.

    Article  PubMed  Google Scholar 

  13. Guckenberger M, Meyer J, Wilbert J, et al. Precision of image-guided radiotherapy (IGRT) in six degrees of freedom and limitations in clinical practice. Strahlenther Onkol 2007;183:307–13.

    Article  PubMed  Google Scholar 

  14. Hoskin PJ, Motohashi K, Bownes P, et al. High dose rate brachytherapy in combination with external beam radiotherapy in radical treatment of prostate cancer: initial results of a randomised phase three trial. Radiother Oncol 2007;84:114–20.

    Article  PubMed  Google Scholar 

  15. ICRU. Report 62: Prescribing, recording and reporting photon beam therapy (supplement to ICRU report 50). Bethesda: International Commission on Radiation Units and Measurements; 1999.

    Google Scholar 

  16. Jereczek-Fossa BA, Vavassori A, Fodor C, et al. Dose escalation for prostate cancer using the three-dimensional conformal dynamic arc technique: analysis of 542 consecutive patients. Int J Radiat Oncol Biol Phys 2008;71: 784–94.

    PubMed  Google Scholar 

  17. Koelbl O, Schwab F, Bratengeier K, et al. Radiotherapy of prostate cancer with multileaf collimators (MLCs): optimization of the undulating dose distribution at the MLC edge. Strahlenther Onkol 2005;181:108–12.

    Article  PubMed  Google Scholar 

  18. Kuban DA, Tucker SL, Dong L, et al. Long-term results of the M.D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 2008;70:67–74.

    PubMed  Google Scholar 

  19. Mock U, Bogner J, Georg D, et al. Comparative treatment planning on localized prostate carcinoma: conformal photon- versus proton-based radiotherapy. Strahlenther Onkol. 2005;181:448–55.

    Article  PubMed  Google Scholar 

  20. Peeters STH, Heemsbergen WD, Koper PCM, 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;24:1990–6.

    Article  PubMed  Google Scholar 

  21. Pollack A, Hanlon AL, Horwitz EM, et al. Prostate cancer radiotherapy dose response: an update of the fox chase experience. J Urol 2004;171:1132–6.

    Article  PubMed  Google Scholar 

  22. Pollack A, Zagars G, Smith LG, et al. Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer. J Clin Oncol 2000;18:3904–11.

    PubMed  CAS  Google Scholar 

  23. Pollack A, Zagars GK, Starkschall G, et al. Prostate cancer radiation dose response: results of the M.D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys 2002;53:1097–105.

    Article  PubMed  Google Scholar 

  24. Reibenwein J. Risikoadaptierte konformale Strahlentherapie des Prostatakarzinoms mit neoadjuvanter Hormontherapie im Rahmen einer multi-center Phase II Studie: Korrelation von späten gastrointestinalen Nebenwirkungen und Rektoskopiebefunden mit Dosis-Volumen-Histogrammen des Rektums. Diplomarbeit 2005. Wien: Universitätsbibliothek, 2005: WJ-D2005-5.

    Google Scholar 

  25. Roach M3rd, Hanks G, Thames HJr, et al. 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 2006;65:965–74.

    PubMed  Google Scholar 

  26. Roach M3rd. Dose escalated external beam radiotherapy versus neoadjuvant androgen deprivation therapy and conventional dose external beam radiotherapy for clinically localized prostate cancer: do we need both? Strahlenther Onkol 2007183 (Spec No 2):26–8.

    Article  PubMed  Google Scholar 

  27. Sathaya JR, Davis IR, Julian JA, et al. 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 2005;23:1192–9.

    Article  Google Scholar 

  28. Schulte RW, Slater JD, Rossi CJ, et al. Value and perspectives of proton radiation therapy for limited stage prostate cancer. Strahlenther Onkol 2000;176:3–8.

    Article  PubMed  CAS  Google Scholar 

  29. Shipley WU, Verhey LJ, Munzenrider JE, et al. Advanced prostate cancer: the results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone. Int J Radiat Oncol Biol Phys 1995;32:3–12.

    PubMed  CAS  Google Scholar 

  30. Shu H-KG, Lee TT, Vigneault E, et al. Toxicity following high-dose three-dimensional conformal and intensity-modulated radiation therapy for clinically localized prostate cancer. Urology 2001;57:102–7.

    Article  PubMed  CAS  Google Scholar 

  31. Sterzing F, Schubert K, Sroka-Perez G, et al. Helical tomotherapy. Experiences of the first 150 patients in Heidelberg. Strahlenther Onkol 2008;184: 8–14.

    Article  PubMed  Google Scholar 

  32. Wachter S, Gerstner N, Goldner G, et al. Rectal sequelae after conformal radiotherapy of prostate cancer: dose-volume histograms as predictive factors. Radiother Oncol 2001;59:65–70.

    Article  PubMed  CAS  Google Scholar 

  33. Yeoh EE, Holloway R, Fraser RJ, et al. Hypofractionated versus conventionally fractionated radiation therapy for prostate carcinoma: updated results of a phase III randomized trial. Int J Radiat Oncol Biol Phys 2006;66: 1072–83.

    PubMed  Google Scholar 

  34. Zelefsky MJ, Chan H, Hunt M, et al. Long-term outcome of high dose intensity modulated radiation therapy for patients with clinically localized prostate cancer. J Urol 2006;176:1415–9.

    Article  PubMed  Google Scholar 

  35. Zelefsky MJ, Leibel SA, Gaudin PB, et al. Dose escalation with three dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys 1998;41:491–500.

    Article  PubMed  CAS  Google Scholar 

  36. Zelefsky MJ, Levin EJ, Hunt M, et al. Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 2008;70:1124–9.

    PubMed  Google Scholar 

  37. Zelefsky MJ, Moughan J, Owen J, et al. Changing trends in national practice for external beam radiotherapy for clinically localized prostate cancer: 1999 patterns of care survey for prostate cancer. Int J Radiat Oncol Biol Phys 2004;59:1053–61.

    Article  PubMed  Google Scholar 

  38. Zietman AL, DeSilvio ML, Slater JD, et al. Comparison of conventional-dose vs. high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA 2005;294:1233–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiotherapy and Radiobiology, Vienna General Hospital, University of Vienna Medical School, Vienna, Austria

    Gregor Goldner MD, Valentin Bombosch, Stefan Wachter, Natascha Wachter-Gerstner & Richard Pötter

  2. Department of Radiotherapy, Technical University, Munich, Germany

    Hans Geinitz, Frank Zimmermann & Michael Molls

  3. Department of Radiotherapy, Hospital am Eichert, Göppingen, Germany

    Gerd Becker

  4. Department of Radiotherapy, University of Tübingen, Tübingen, Germany

    Stefan Glocker & Michael Bamberg

  5. Statistikambulanz, Leobendorf, Austria

    Andrea Schrott

  6. Department of Radiotherapy, General Hospital Fulda, Fulda, Germany

    Horst Feldmann

  7. Department of Radiotherapy and Radiobiology, University Hospital of Vienna, Währinger Gürtel 18–20, 1090, Vienna, Austria

    Gregor Goldner MD

Authors
  1. Gregor Goldner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valentin Bombosch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hans Geinitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gerd Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stefan Wachter
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Stefan Glocker
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Frank Zimmermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Natascha Wachter-Gerstner
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andrea Schrott
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michael Bamberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Michael Molls
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Horst Feldmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Richard Pötter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gregor Goldner MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Goldner, G., Bombosch, V., Geinitz, H. et al. Moderate risk-adapted dose escalation with three-dimensional conformal radiotherapy of localized prostate cancer from 70 to 74 Gy. Strahlenther Onkol 185, 94–100 (2009). https://doi.org/10.1007/s00066-009-1970-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-009-1970-3

Key Words:

Schlüsselwörter:

Search

Navigation