Long-term results of the Dutch randomized prostate cancer trial: impact of dose-escalation on local, biochemical, clinical failure, and survival.
OBJECTIVE
Nowadays, advanced irradiation techniques make it possible to escalate safely the dose in prostate cancer. We studied the effect of a higher dose on tumor control in a randomized trial with a median follow-up of 110 months.


METHODS
Patients with T1b-T4N0 prostate cancer (n=664) were randomized between 78 Gy and 68 Gy. Primary endpoint was biochemical and/or clinical failure (BCF) according to the American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines (3 consecutive rises), and to Phoenix (nadir plus 2 μg/L). Secondary endpoints were clinical failure (CF), local failure (LF), prostate cancer death (PCD), and overall survival (OS). Explorative subgroup analyses were performed.


RESULTS
BCF rate (HR=0.8; 20% less events) and LF rate (HR=0.5; 50% less events) were significantly lower in the 78 Gy arm (p<0.05). CF, PCD and OS were similar in both arms. A significant heterogeneity of treatment effect was found for PSA cutoffs between 7 and 10 μg/L.


CONCLUSIONS
We observed significantly less BCF and LF in the high-dose arm. This suggests improvement of the therapeutic ratio. However, we observed similar rates of CF and PCD at the current update. More follow-up is needed to investigate which patients benefit in terms of prolonged OS.
Department of Radiation Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Electronic address: w.heemsbergen@nki.nl.
Wilma D
WD
Heemsbergen
Department of Radiation Oncology, Erasmus MC - Cancer Institute, Rotterdam, The Netherlands.
Abrahim
A
Al-Mamgani
Radiotherapeutic Institute Friesland, Leeuwarden, The Netherlands.
Annerie
A
Slot
Zeeuws Radiotherapeutic Institute, Vlissingen, The Netherlands.
Michel F H
MF
Dielwart
Department of Radiation Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Joos V
JV
Lebesque
D000368:Aged; D000369:Aged, 80 and over; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D015996:Survival Rate; D017211:Treatment Failure
C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
Clinical trial; Dose-escalation; Prostate cancer