Strahlentherapie und Onkologie

, Volume 185, Issue 2, pp 94–100

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
  • Gregor Goldner
  • Valentin Bombosch
  • Hans Geinitz
  • Gerd Becker
  • Stefan Wachter
  • Stefan Glocker
  • Frank Zimmermann
  • Natascha Wachter-Gerstner
  • Andrea Schrott
  • Michael Bamberg
  • Michael Molls
  • Horst Feldmann
  • Richard Pötter
Original Article

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.

Key Words:

Prostate cancer 3D-CRT Toxicity bNED Outcome 

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

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.

Schlüsselwörter:

Prostatakarzinom 3D-CRT Nebenwirkungen Ergebnisse bNED 

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Copyright information

© Urban & Vogel, Muenchen 2009

Authors and Affiliations

  • Gregor Goldner
    • 1
    • 7
  • Valentin Bombosch
    • 1
  • Hans Geinitz
    • 2
  • Gerd Becker
    • 3
  • Stefan Wachter
    • 1
  • Stefan Glocker
    • 4
  • Frank Zimmermann
    • 2
  • Natascha Wachter-Gerstner
    • 1
  • Andrea Schrott
    • 5
  • Michael Bamberg
    • 4
  • Michael Molls
    • 2
  • Horst Feldmann
    • 6
  • Richard Pötter
    • 1
  1. 1.Department of Radiotherapy and RadiobiologyVienna General Hospital, University of Vienna Medical SchoolViennaAustria
  2. 2.Department of RadiotherapyTechnical UniversityMunichGermany
  3. 3.Department of RadiotherapyHospital am EichertGöppingenGermany
  4. 4.Department of RadiotherapyUniversity of TübingenTübingenGermany
  5. 5.StatistikambulanzLeobendorfAustria
  6. 6.Department of RadiotherapyGeneral Hospital FuldaFuldaGermany
  7. 7.Department of Radiotherapy and RadiobiologyUniversity Hospital of ViennaViennaAustria

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