Short vs Long?
The RADICALS-HD, multicenter open label randomized control trial, investigated the necessity and duration of androgen deprivation therapy (ADT) in combination with postoperative radiotherapy (RT) after radical prostatectomy in prostate cancer patients.
The study compared three approaches: no ADT (None), 6-month ADT (Short), and 24-month ADT (Long). The primary outcome was metastasis-free survival (MFS), with secondary outcomes included freedom from distant metastasis, overall survival, and initiation of nonprotocol ADT.
Between 2007 and 2015, 492 participants were randomly assigned to one of the three groups: 166 to None, 164 to Short, and 162 to Long. The median age was 66 years, and most had intermediate-risk prostate cancer based on Gleason scores. The median follow-up was nine years.
The trial found no significant difference in MFS among the three groups. After 10 years, 80.1% of the None group, 76.8% of the Short group, and 80.7% of the Long group were free from metastatic disease. The hazard ratio (HR) for Long vs. None was 0.95 (95% confidence interval: 0.54–1.68), indicating no clear benefit from prolonged ADT. Similarly, no significant differences were found in overall survival (log-rank p = 0.94) or freedom from distant metastases.
Although the study was not fully powered to assess the None vs. Long comparison definitively, its results suggest that ADT does not significantly improve long-term outcomes in patients eligible for randomization.
The trial supports the notion that postoperative RT alone may be sufficient for many patients, particularly those with favorable characteristics (lower pre-RT PSA, longer time since radical prostatectomy, and lower Gleason score). If ADT is used, a longer duration (24 months) may be preferable to six months. The findings suggest revising clinical guidelines to refine ADT use in postoperative RT, emphasizing patient selection based on risk factors.
Overall, RADICALS-HD reinforces that many men undergoing postoperative RT after radical prostatectomy have favorable outcomes, and future trials should target higher-risk patients to determine who benefits most from ADT.
Table 1: Summary of RADICALS-HD trails
Outcome | Group | Events | 10-Year Event-Free (%) | Restricted mean survival time (Years) | Log-rank p-value | Hazard Ratio (95% CI) vs. None |
Metastasis-Free Survival (MFS) | None | 32 | 81% | 9.18 (8.89–9.47) | 0.98 | NA |
Short | 31 | 77% | 9.14 (8.84–9.44) | 1.01 (0.57–1.76) | ||
Long | 26 | 81% | 9.22 (8.91–9.53) | 0.95 (0.54–1.68) | ||
Overall Survival (OS) | None | 22 | 85% | 9.43 (9.18–9.68) | 0.94 | NA |
Short | 23 | 82% | 9.39 (9.14–9.64) | 1.12 (0.59–2.16) | ||
Long | 21 | 85% | 9.44 (9.18–9.69) | 1.07 (0.54–2.12) | ||
Freedom from Distant Metastasis (FFDM) | None | 16 | 91% | 9.58 (9.36–9.80) | 0.77 | NA |
Short | 13 | 91% | 9.60 (9.39–9.82) | 0.79 (0.33–1.89) | ||
Long | 13 | 89% | 9.54 (9.28–9.80) | 1.09 (0.50–2.37) | ||
Time to Salvage Hormone Therapy (SHT) | None | 38 | 76% | 8.42 (7.95–8.88) | 0.026 | NA |
Short | 26 | 76% | 9.11 (8.78–9.43) | +0.81 years (0.24–1.38) | ||
Long | 22 | 83% | 9.35 (9.08–9.63) | +0.90 years (0.36–1.44) |
Dr Ketan Kapoor
VMMC & SJH, New Delhi
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