ASCO 2019: Interest of Short Hormonotherapy Associated with Radiotherapy as Salvage Treatment for Metastatic-Free Survival after Radical Prostatectomy: Update at Nine Years of the GETUG-AFU 16 Phase III Randomized Trial

Chicago, IL ( Nicolas Magné, MD presented the 9-year update of the GETUG-AFU 16 phase three randomized trial. He began with a short background, explaining that approximately 30% of patients with prostate cancer relapse after radical prostatectomy with a rising PSA level. They usually have no evidence of clinical or radiographic disease, and eventually, develop distant metastases within eight years.1   Salvage radiotherapy is the standard of care in patients with PSA-only relapse, resulting in 35% of patients not having a biological relapse at five years,2 and delaying the time to long term androgen deprivation therapy (ADT).

Retrospective data has suggested an improved outcome if short ADT is added to radiotherapy in high-relapse risk patients. The RTOG 9601 study3 demonstrated an improved overall survival (OS) at 12 years after two years of ADT plus radiotherapy in patients with persistent PSA following radical prostatectomy.

In the presented trial by Dr. Magné, the efficacy of radiotherapy was compared to that of radiotherapy + short duration ADT (6 months). The study design and inclusion criteria are shown in Figure 1. This was a randomized, open-label, multicenter phase 3 study. The patients were stratified according to:
  • Investigational Site
  • Intensity-modulated radiotherapy (IMRT) vs. Three Dimensional (3D) Conformal
  • Radiation therapy (3D RT)
  • High risk vs. low risk
Low-risk disease was defined as:
  • Gleason score<8
  • Positive surgical margins
  • PSA doubling time at relapse of more than six months
  • No seminal vesicle invasion
The study’s primary endpoint was progression-free survival (PFS): time from randomization to biological or clinical progression or death. The secondary objectives included:
  • Metastasis-free survival (MFS)
  • OS
  • Acute and late toxicities
  • Quality of life
Figure 1 – GETUG-AFU 16 study design and inclusion criteria:
ASCO 2019 GETUG AFU 16 study designAfter an update in 2008, the study planned to accrue 738 patients with 369 events, with a power of 80% for 10% gain in OS. Eventually, 743 patients were randomized between 2006 and 2010 in an impressive 43 French centers. The updated median follow-up is 112 months (IQR 102-123), and the delay between radical prostatectomy and relapse was shown to be 40 months (SD 27). The baseline characteristics were similar in both trial arms.

The updated PFS results in 2019 are shown in figure 2, with a clear benefit in the radiotherapy with ADT group (80% vs. 63% and 64% vs. 49% for 5- and 10-year PFS, respectively). The hazard ratio is 0.54 (95% CI 0.43-0.68, p<0.0001). The MFS also showed a benefit for the radiotherapy + ADT group, with a hazard ratio of 0.73 (95% CI 0.54-0.98), p=0.034) (Figure 3). In contrast, no difference was shown in the updated OS results (figure 4).

Figure 2 – Progression-free survival – updated 2019 results:

ASCO 2019 GETUG AFU 16 progression free survival

Figure 3- Metastasis-free survival – updated 2019 results:

ASCO 2019 GETUG AFU 16 Metastasis free survival

Figure 4- Overall survival – updated 2019 results:

ASCO 2019 GETUG AFU 16 overall free survival

In conclusion, short ADT combined with radiotherapy increase the 10-year MFS compared to radiotherapy alone in patients with rising PSA after radical prostatectomy. This significant improvement enables to postpone more aggressive treatment such as long-term ADT with its associated deleterious effect on patient quality of life.

Presented by: Nicolas Magné, MD, Radiotherapy Department, Centre Léon Bérard, Lyon, France

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

  1. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural History of Progression After PSA Elevation Following Radical Prostatectomy. JAMA. 1999;281(17):1591–1597. doi:10.1001/jama.281.17.1591
  2. Stephenson AJ, Scardino PT, Kattan MW, et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol. 2007;25(15):2035–2041. doi:10.1200/JCO.2006.08.9607
  3. Jang et al. Int J Radiat Oncol Biol Phys 2012