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