GETUG-AFU-18 is another trial where the findings are obvious, and irrelevant, because radiation and hormone medication technology have improved far beyond what was available when this trial began 15 years ago, and long follow-ups are necessary to detect outcome differences in men with localized prostate cancer. A similar trial (RTOG 0126) in intermediate-risk patients found a curative benefit for the higher dose, although no increase in overall survival within 8 yearsd.
The trial randomized 505 high-risk patients in 25 French centers to receive a radiation dose of either 70 Gy or 80 Gy.
- All patients received 3 years of ADT. (If started today, it may have been 2 years of ADT (see this link) with external beam radiation.)
- All patients had no detectable cancer in pelvic lymph nodes (N0), but 83% received whole pelvic radiation.
- High-dose patients received IMRT, but many (41%) lower dose patients received 3D-CRT (which is seldom used anymore).
After 10 years of follow-up, only 92 men progressed, which was less than expected. The results were:
- 84% were progression-free in the 80 Gy arm, 72% in the 70 Gy arm.
- 44% reduction in the biochemical failure rate
- 52% reduction in prostate cancer-specific mortality
- 39% reduction in overal mortality rate
- No difference in late-term urinary or rectal toxicity. Serious (grade 3) toxicity was rare (2-3%)
- No difference in patient-reported quality of life
It comes as no surprise that higher dose radiation to the prostate is more curative. Since there is no toxicity cost to giving the higher dose, it is the clear standard of care.
Several randomized clinical trials (ASCENDE-RT and TROG RADAR) have now proven that increasing the prostate dose with brachytherapy improves outcomes. Clinical trials using SBRT for high-risk patients are underway, and moderate hypofractionation is already standard of care. The FLAME trial showed results can be improved by targeting MRI-detected intraprostatic lesions with a radiation boost. POP-RT showed the importance of whole-pelvic treatment. The whole-pelvic treatment area was expanded (see this link).
STAMPEDE showed that 3 years of abiraterone+ 2 years of ADT improved results over ADT alone. Hormone treatment has been intensified and shortened in the AASUR trial. The PREDICT-RT trial investigates Decipher genomic scores to determine intensity and duration of hormone treatment with apalutamide. DASL-HiCAP tests darolutamide.
The FDA approval of PSMA PET/CT for high-risk patients improves patient selection. Those found to have distant metastases might be better treated with hormone therapy alone. Those found to have only pelvic lymph node metastases might still be curatively treated with radiation and hormone therapy.