Radiotherapy is the standard salvage treatment after radical prostatectomy. To date, the role of androgen deprivation therapy has not been formally shown. In this follow-up study, we aimed to update the results of the GETUG-AFU 16 trial, which assessed the efficacy of radiotherapy plus androgen suppression versus radiotherapy alone.
GETUG-AFU 16 was an open-label, multicentre, phase 3, randomised, controlled trial that enrolled men (aged ≥18 years) with Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed adenocarcinoma of the prostate (but no previous androgen suppression or pelvic radiotherapy), stage pT2, T3, or T4a (bladder neck involvement only) and pN0 or pNx according to the tumour, node, metastasis (TNM) staging system, whose prostate-specific antigen (PSA) concentration increased from 0·1 ng/mL to between 0·2 ng/mL and 2·0 ng/mL after radical prostatectomy, without evidence of clinical disease. Patients were assigned through central randomisation (1:1) to short-term androgen suppression (subcutaneous injection of 10·8 mg goserelin on the first day of irradiation and 3 months later) plus radiotherapy (3D conformal radiotherapy or intensity modulated radiotherapy of 66 Gy in 33 fractions, 5 days a week for 7 weeks) or radiotherapy alone. Randomisation was stratified using a permuted block method (block sizes of two and four) according to investigational site, radiotherapy modality, and prognosis. The primary endpoint was progression-free survival in the intention-to-treat population. This post-hoc one-shot data collection done 4 years after last data cutoff included patients who were alive at the time of the primary analysis and updated long-term patient status by including dates for first local progression, metastatic disease diagnosis, or death (if any of these had occurred) or the date of the last tumour evaluation or last PSA measurement. Survival at 120 months was reported. Late serious adverse effects were assessed. This trial is registered on ClinicalTrials.gov, NCT00423475.
Between Oct 19, 2006, and March 30, 2010, 743 patients were randomly assigned, 374 to radiotherapy alone and 369 to radiotherapy plus goserelin. At the time of data cutoff (March 12, 2019), the median follow-up was 112 months (IQR 102–123). The 120-month progression-free survival was 64% (95% CI 58–69) for patients treated with radiotherapy plus goserelin and 49% (43–54) for patients treated with radiotherapy alone (hazard ratio 0·54, 0·43–0·68; stratified log-rank test p<0·0001). Two cases of secondary cancer occurred since the primary analysis, but were not considered to be treatment related. No treatment-related deaths occurred.
The 120-month progression-free survival confirmed the results from the primary analysis. Salvage radiotherapy combined with short-term androgen suppression significantly reduced risk of biochemical or clinical progression and death compared with salvage radiotherapy alone. The results of the GETUG-AFU 16 trial confirm the efficacy of androgen suppression plus radiotherapy as salvage treatment in patients with increasing PSA concentration after radical prostatectomy for prostate cancer.
When prostate cancer comes back after a radical prostatectomy (= an operation to remove prostate cancer), radiotherapy is the standard second attempt to treat prostate cancer with. However, another possible therapy is an antihormone treatment called androgen deprivation therapy. In this article, the authors describe the clinical trial they have conducted in which they assessed the impact of androgen deprivation therapy given simultaneously with radiotherapy on prostate cancer that has come back. The results were positive: patients who had received the combined treatment had better outcomes: they lived longer without the cancer getting worse, and they didn’t develop tumours in other parts of the body. Therefore, six months of androgen deprivation therapy simultaneous with radiotherapy should be considered the norm. The next step should be to identify patients who would benefit the most from this method in order to reduce the risks of overtreatment and the occurrence of negative effects linked to androgen deprivation therapy.