Elsevier

The Lancet

Volume 360, Issue 9327, 13 July 2002, Pages 103-108
The Lancet

Articles
Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial

https://doi.org/10.1016/S0140-6736(02)09408-4Get rights and content

Summary

Background

We did a randomised phase III trial comparing external irradiation alone and external irradiation combined with an analogue of luteinising-hormone releasing hormone (LHRH) to investigate the added value of long-term androgen suppression in locally advanced prostate cancer.

Methods

Between 1987 and 1995, 415 patients were randomly assigned radiotherapy alone or radiotherapy plus immediate androgen suppression. Eligible patients had T1–2 tumours of WHO grade 3 or T3–4 N0–1 M0 tumours; the median age of participants was 71 years (range 51–80). In both treatment groups, 50 Gy radiation was delivered to the pelvis over 5 weeks, and 20 Gy over 2 weeks as a prostatic boost. Goserelin (3·6 mg subcutaneously every 4 weeks) was started on the first day of irradiation and continued for 3 years; cyproterone acetate (150 mg orally) was given for 1 month starting 1 week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analyses were by intention to treat.

Findings

412 patients had evaluable data, with median follow-up of 66 months (range 1–126). 5-year clinical disease-free survival was 40% (95% CI 32–48) in the radiotherapy-alone group and 74% (67–81) in the combined-treatment group (p=0·0001). 5-year overall survival was 62% (52–72) and 78% (72–84), respectively (p=0·0002) and 5-year specific survival 79% (72–86) and 94% (90–98).

Interpretation

Immediate androgen suppression with an LHRH analogue given during and for 3 years after external irradiation improves disease-free and overall survival of patients with locally advanced prostate cancer.

Introduction

The long-term outcome after external irradiation alone in locally advanced prostate cancer, staged T3–4N0M0 according to the classification of the International Union against Cancer1 is poor,2 especially for biochemically defined disease-free survival.3 From the mid-1980s, two approaches to improve these results were investigated: first, the combination of androgen suppression and external irradiation in an attempt to decrease the local failure rate and to destroy hormone-dependent micrometastases outside the planning target volume; and second, three-dimensional conformal radiotherapy to improve local control,4 by increasing the dose delivered to the prostate. Three phase III randomised trials have shown an improvement of overall survival with the combination of radiotherapy and androgen suppression. For two of these trials,5, 6 this improvement was greatest for a subset of patients with Gleason 8–10 T2c–T4 tumours, whereas an EORTC trial7 found a significant difference in 5-year overall survival, irrespective of the histological grade. Here, we present the long-term results of this trial, with a multivariate prognostic-factor analysis, and assessment of the serum testosterone profile after the end of the long-term androgen suppression.

Section snippets

Patients

Eligible patients were younger than 80 years, with histologically proven T1–2 prostatic adenocarcinoma of WHO histological grade 3, or T3–4 prostatic adenocarcinoma of any histological grade. The clinical investigation was based on bone scan, chest radiograph, and ultrasonography or CT of the abdomen. Lymph nodes were assessed by CT scan, bipedal lymphangiography, or extraperitoneal lymphadenectomy. The laboratory studies included complete blood count and measurements of creatinine, serum

Results

Between May, 1987, and September, 1995, 415 patients entered the study: 208 were randomly assigned to the radiotherapy-alone group and 207 to the combined-treatment group (figure 1). At the time of the analysis reported here, median duration of follow-up was 66 months (range 1–126). 412 patients could be centrally evaluated and 11 were ineligible (four assigned combined treatment and seven assigned radiotherapy alone). The reasons for ineligibility were incomplete examination before

Discussion

The combination of 3 years of androgen suppression with external irradiation was associated with better 5-year overall survival of locally advanced prostate cancer than radiotherapy alone. These updated results, with median follow-up of 65·7 months, accord with those reported in 1996, when the median follow-up was 33 months,12 and in 1997 with median follow-up of 45 months.8 Androgen suppression provides a method to improve the outcome of external irradiation alone, possibly by elimination of

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