No one wants androgen deprivation therapy (ADT) along with ("adjuvant to") salvage radiation therapy (SRT). We are accumulating evidence about how long one needs to stay on it to prevent the cancer from coming back, but judgment is still necessary.
There are some situations where it is unclear that SRT is needed at all (discussed in this link). This includes: a very long time (>18 months) before biochemical recurrence (BCR), slow doubling time, low Gleason score, elderly, significant comorbidities, no metastases with PSMA PET, and low Decipher score.
6 months ADT somewhat better than none
GETUG-16 (article here) found that 6 months of ADT is better than no ADT. Incidence of metastases was improved by 27% among 743 patients. Whole pelvic radiation was at the doctor's discretion.
SPPORT (RTOG 0534) found that 4-6 months was beneficial for everyone and that there was no difference between 4 and 6 months. It was a very large trial (n=1,762) and used 8-year Freedom from Progression (mostly PSA) as its primary endpoint. A third of patients received whole pelvic radiation.
RADICALS-HD found that 6 months was no more beneficial than none! This was a large trial (n=1,500) that ran for 15 years. It used Metastasis Free Survival (MFS) as its primary endpoint. There was an 11% improvement in incidence of metastases which was not statistically significant. Only 15% received whole pelvic radiation.
DADSPORT meta-analysis sought to resolve the conflicting findings by combining the results of all 3 trials. It found an 18% improvement in incidence of metastases.
The endpoint and the follow-up are important. For men who are aged 60-70 at the time of prostatectomy, none of the trials had long enough follow-up to detect a difference in overall survival. MFS improvement may be small in the short-run, but metastases may appear later and adversely affect quality of life. Those who want to be definitively cured (i.e., no evidence of disease as evinced by PSA) should have at least short-term ADT.
24 months of ADT slightly better than 6 months
RTOG 9601 showed that 24 months of adjuvant ADT did not improve survival when postprostatectomy PSA was below 0.7 ng/ml. A recent analysis by Spratt et al. suggested that adjuvant ADT is always necessary when PSA ≥ 1.5 ng/ml, but that risks may outweigh benefits when PSA is lower than 0.6 ng/ml. There were 760 patients with 13 years of follow-up. The primary endpoint was overall survival.
RADICALS-HD showed that 24 months of ADT improved survival over none or 6 months. 10-year MFS improved from 72% to 78%, while incidence of metastases declined by 23%. In the subgroup that had a PSA>0.5, incidence of metastases declined by 33%.
So 24 months of ADT is better than 6 months or none if one's goal is to avoid metastases.
8 months (36 weeks) of ADT with enzalutamide
The EMBARK trial found that by intensifying ADT with enzalutamide (Xtandi) compared to ADT alone, the MFS improved by 58%, and PSA-free survival improved by 97% with 61 months of follow-up.
12 months of ADT with apalutamide
The PRESTO trial found that by intensifying ADT with apalutamide (Erleada) compared to ADT alone, biochemical (PSA) recurrence-free survival (bRFS) improved by 48% with 21 months of follow-up.
6 months of ADT with apalutamide and abiraterone