Einleitung
Eine kontroverse Fragestellung im Bereich der Prostatakrebsbehandlung betrifft den Einfluss hochdosiger Strahlentherapie in Kombination mit langfristiger Androgens-Abwertungstherapie (ADT). Ein neues Studium hat nun diese Frage untersucht und zeigt, dass eine höhere Strahlendosis eine bessere Progresaufsetzung über längere Zeiträume verhindern kann.
Studienergebnisse & Methodik
Die GETUG AFU 18-Studie war eine mehrzentrale, offene, zufallsgeteilt und phasen 3-Präzision. 505 Patienten mit hochriskierter Prostatakrebsfunktion (Prostata-Spezifischer Antigen (PSA) von 20 ng/mL oder höher, Gleason-Score 8 oder höher, oder klinische T3-T4-Phase) wurden in zwei Gruppen eingeteilt. 250 Patienten erhielten eine 10 Gy höhere Strahlendosis (80 Gy in 8 Wochen, 2 Gy pro Fraktion) und 255 Patienten eine Standarddosis (70 Gy in 7 Wochen, 2 Gy pro Fraktion) kombiniert mit langfristiger ADT. Die primäre Endpunktanalyse betrachtete den 5-jährigen Progresaufsetzungsunterschied. Die Studie zeigte, dass das 5-jährige Progresaufsetzungsunternehmen in der hochdosigen Strahlungsgruppe 91,4% betrug, im Standarddosis-Untersuchungsgruppe 88,1%, und das 10-jährige Progresaufsetzungsunternehmen 83,6% im Hochdosigungsgruppe und 72,2% im Kontrollgruppe.
Kritische Einordnung
Die Studie belegt, dass eine höhere Strahlendosis eine bessere Progresaufsetzung verhindern kann. Allerdings ist die Anzahl der Ereignisse niedrig, sodass weitere Forschungen erforderlich sind, um die genaue Auswirkung auf Prostatakrebs- und allgemeine Überlebenszeit zu bestätigen. Die Adverse Ereignisse in der Gruppe der hochdosigen Strahlung waren leicht höher, aber nicht kritisch.
Praxis-Fazit
- Prostatakrebspatienten sollten sich beraten lassen, ob eine höhere Strahlendosis eine bessere Therapiemöglichkeit ist.
- Langfristige ADT sollte bei hochriskierter Prostatakrebspatienten standardmäßig mit Strahlentherapie kombiniert werden.
- Patienten sollten vor der Behandlung präzise Informationen erhalten, um ihre Erwartungen zu managen.
Original-Abstract (Englisch)
BACKGROUND: For patients with high-risk prostate cancer, the role of dose-escalated radiotherapy in combination with long-term androgen deprivation treatment (ADT) is controversial, without any demonstrated benefit on cancer-specific or overall survival. We aimed to evaluate the effect of a 10 Gy dose increase, from 70 Gy to 80 Gy, on progression-free survival in men with high-risk prostate cancer.
METHODS: In this multicentre, open-label, randomised, phase 3 trial, we enrolled patients with high-risk prostate cancer, defined as prostate-specific antigen of 20 ng/mL or more, Gleason score of at least 8, or clinical stage T3-T4, from 25 centres in France. Participants were randomly assigned (1:1) by minimisation, stratified by centre and previous pelvic lymph node dissection, to receive prostate-targeted dose-escalated external beam radiotherapy (80 Gy; 2 Gy per fraction for 8 weeks) or standard-dose external beam radiotherapy (70 Gy; 2 Gy per fraction for 7 weeks), combined with long-term ADT. Neither the participants nor the investigators were masked to the allocated treatment. The primary endpoint was 5-year progression-free survival defined as the time from randomisation to first biochemical (defined as prostate-specific antigen >nadir plus 2 ng/mL) or clinical (ie, local, regional, or metastatic) disease progression, analysed in the intention-to-treat population, with 197 events required. 5-year progression-free survival was the prespecified endpoint, and 10-year progression-free survival was additionally reported (post hoc) in view of the low number of events at 5 years. The trial is registered at ClinicalTrials.gov, NCT00967863, and is complete.
FINDINGS: Between April 6, 2009, and Jan 24, 2013, 505 patients with high-risk prostate cancer were enrolled; 250 were assigned to receive dose-escalated radiotherapy (80 Gy) and 255 to receive standard dose radiotherapy (70 Gy). All participants were male and ethnicity data were not collected. At a median follow-up of 9·5 years (IQR 8·5-10·3), 5-year progression-free survival was 91·4% (95% CI 87·0-94·4) in the dose-escalation group versus 88·1% (83·2-91·6) in the control group, and 10-year progression-free survival was 83·6% (77·8-88·0) versus 72·2% (65·3-78·0; stratified HR 0·56, 95% CI 0·40-0·78, p<0·0001). Grade 3 or worse adverse events assessed at 6 months (acute toxicity) were observed in 60 (24%) of patients in the dose-escalation group and 62 (25%) in the control group. The most frequent grade 3 or worse adverse events were sexual disorders (28 [11%] in the dose-escalation group vs 20 [8%] in the control group) and bladder or urethra disorders (12 [5%] vs 19 [8%]). Adverse events assessed at 5 years (late toxicity) occurred in 118 (70%) of 168 in the dose-escalation group and 122 (73%) of 168 in the control group; grade 3 or worse late toxicities occurred in 19 (8%) participants in the dose-escalated radiotherapy group versus 17 (7%) participants in the control group. The most common late grade 3 adverse event was bladder or urethra disorders (seven [4%] vs three [2%], respectively). Serious adverse events occurred in nine (4%) patients in the dose escalation group and nine (4%) in the control group; none were considered to be treatment related. There were no treatment-related deaths.
INTERPRETATION: For patients with high-risk prostate cancer, radiotherapy at a total dose of 80 Gy, in combination with long-term ADT, improved progression-free survival and could be a potential option in this situation. However, given the low number of events, further research is needed to consolidate and confirm the benefit in dose-escalation in prostate cancer-specific survival and overall survival.
FUNDING: French National Cancer Institute and AstraZeneca.
