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Lancet Oncol. 2015 Mar;16(3):320-7. doi: 10.1016/S1470-2045(15)70045-8. Epub 2015 Feb 19.

High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial.

Author information

1
Hospital Universitario de la Princesa, Madrid, Spain. Electronic address: almudena.zapatero@salud.madrid.org.
2
Hospital Son Espases, Palma de Mallorca, Spain.
3
Hospital Universitari Vall d'Hebron, Barcelona, Spain.
4
Hospital General Universitario Gregorio Marañón, Madrid, Spain.
5
Hospital Universitario 12 de Octubre, Madrid, Spain.
6
Hospital General de Catalunya, Sant Cugat del Vallès and Hospital Universitario de Salamanca, Salamanca, Spain.
7
Hospital Plató, Barcelona, Spain.
8
Hospital Clinic, Barcelona, Spain.
9
Institut Català d'Oncologia, Barcelona, Spain.
10
Hospital Universitario de la Princesa, Madrid, Spain.
11
Hospital Do Meixoeiro, Vigo, Spain.
12
Apices Data Management and Biostatistics Centre, Madrid, Spain.

Abstract

BACKGROUND:

The optimum duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains undefined. We aimed to determine whether long-term androgen deprivation was superior to short-term androgen deprivation when combined with high-dose radiotherapy.

METHODS:

In this open-label, multicentre, phase 3 randomised controlled trial, patients were recruited from ten university hospitals throughout Spain. Eligible patients had clinical stage T1c-T3b N0M0 prostate adenocarcinoma with intermediate-risk and high-risk factors according to 2005 National Comprehensive Cancer Network criteria. Patients were randomly assigned (1:1) using a computer-generated randomisation schedule to receive either 4 months of androgen deprivation combined with three-dimensional conformal radiotherapy at a minimum dose of 76 Gy (range 76-82 Gy; short-term androgen deprivation group) or the same treatment followed by 24 months of adjuvant androgen deprivation (long-term androgen deprivation group), stratified by prostate cancer risk group (intermediate risk vs high risk) and participating centre. Patients assigned to the short-term androgen deprivation group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy (flutamide 750 mg per day or bicalutamide 50 mg per day) was added during the first 2 months of treatment. Patients assigned to long-term suppression continued with the same luteinising hormone-releasing hormone analogue every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175212.

FINDINGS:

Between Nov 7, 2005, and Dec 20, 2010, 178 patients were randomly assigned to receive short-term androgen deprivation and 177 to receive long-term androgen deprivation. After a median follow-up of 63 months (IQR 50-82), 5-year biochemical disease-free survival was significantly better among patients receiving long-term androgen deprivation than among those receiving short-term treatment (90% [95% CI 87-92] vs 81% [78-85]; hazard ratio [HR] 1·88 [95% CI 1·12-3·15]; p=0·01). 5-year overall survival (95% [95% CI 93-97] vs 86% [83-89]; HR 2·48 [95% CI 1·31-4·68]; p=0·009) and 5-year metastasis-free survival (94% [95% CI 92-96] vs 83% [80-86]; HR 2·31 [95% CI 1·23-3·85]; p=0·01) were also significantly better in the long-term androgen deprivation group than in the short-term androgen deprivation group. The effect of long-term androgen deprivation on biochemical disease-free survival, metastasis-free survival, and overall survival was more evident in patients with high-risk disease than in those with low-risk disease. Grade 3 late rectal toxicity was noted in three (2%) of 177 patients in the long-term androgen deprivation group and two (1%) of 178 in the short-term androgen deprivation group; grade 3-4 late urinary toxicity was noted in five (3%) patients in each group. No deaths related to treatment were reported.

INTERPRETATION:

Compared with short-term androgen deprivation, 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy improved biochemical control and overall survival in patients with prostate cancer, particularly those with high-risk disease, with no increase in late radiation toxicity. Longer follow-up is needed to determine whether men with intermediate-risk disease benefit from more than 4 months of androgen deprivation.

FUNDING:

Spanish National Health Investigation Fund, AstraZeneca.

PMID:
25702876
DOI:
10.1016/S1470-2045(15)70045-8
[Indexed for MEDLINE]
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