Table 2.
RCTs assessing the combination of RT and HT.
| Study | Year | Risk | Treatment | N | Volume/Total Dose | Results |
|---|---|---|---|---|---|---|
| RTOG 85-31 [11,12,13] |
1997 2001 2005 |
Mainly HR N+ 30% |
RT alone RT + AHT indefinitely |
977 | If N+: Pelvis +/− PAo 44–46 Gy Prostate/Prostate Bed 65–70 Gy |
Immediate AHT improved LC, MFS, and OS at 10 years |
| RTOG 86-10 [14,15,16] |
1995 2001 2008 |
Mainly HR N+ 8% |
RT alone RT + NA-CHT × 4 months |
471 | Pelvis 45 Gy Prostate 65–70 Gy |
Short course NA-CHT improved BF, DM, and PCSM at 10 years. |
| EORTC 22863 [17,18,19] | 1996 2002 2010 |
Mainly HR | RT alone RT + C-AHT × 36 months |
415 | Pelvis 50 Gy Prostate 70 Gy |
ADT improved DFS, PCSM, and OS at 10 years. No difference in CV deaths. |
| RTOG 92-02 [20,21] |
2003 2008 |
Mainly HR | RT + NA-CHT × 4 months RT + NA-C-AHT × 28 months (ADT started 2 months before RT) |
1554 | Pelvis 44–46 Gy Prostate 65–70 Gy |
Long course HT improved MFS at 10 years. OS was also improved in the Gleason 8–10 subgroup. |
| Crook et al. [22,23] | 2004 2009 |
HR 31% IR 43% LR 26% |
RT + NAHT × 3 months RT + NAHT × 8 months |
378 | If N+ risk > 10–15%: Pelvis 45–46 Gy Prostate: 66–67 Gy |
Long course NAHT did not improve DFS at 5 years, except in the HR subgroup. |
| TROG 96.01 [24,25] | 2005 2011 |
HR 84% IR 16% |
RT Alone RT + NA-CHT × 3 months RT + NA-CHT × 6 months |
818 | Prostate 66 Gy No Pelvis |
NA-CHT improved DM, PCSM, and 10-year all-cause mortality when given for 6 months. This was not seen in the 3-months arm. |
| EORTC 22961 [26] | 2009 | Mainly HR N+ 8% |
RT + C-AHT × 6 months RT + C-AHT × 36 months |
970 | Pelvis 50 Gy Prostate 70 Gy |
Short course ADT is inferior for OS and CSS at 5 years. |
| PCS IV [27] | 2018 | HR | RT + NA-C-AHT × 36 months RT + NA-C-AHT × 18 months ADT started 4 months before RT |
630 | Pelvis 44 Gy Prostate 70 Gy |
36-month ADT course is not superior to an 18-month course in OS at 5 years |
| DART 01/05 GICOR [28,29] | 2015 2022 |
HR 53% IR 47% |
DE-RT + NA-CHT × 4 months DE-RT + NA-C-AHT × 28 months |
354 | Pelvis (optional, treated in 12–16%) Prostate 76–82 Gy |
Better OS with a 28-month course at 5 years. At 10 years, clinically relevant OS benefits in HR (NSS) but not in IR. |
| TROG 03-04 RADAR [30,31,32] | 2015 2019 2020 |
HR 66.3% UIR 31.4% FIR 2.3% |
RT + NA-CHT × 6 months +/− Adjuvant Zoledronic Acid × 18 months RT + NA-C-AHT × 18 months +/− Adjuvant Zoledronic Acid × 18 months |
1071 | Prostate 66 Gy, 70 Gy, 74 Gy or EBRT + HDRB 46 Gy + 6.5 Gy × 3 (EQD2 88 Gy) No pelvis |
Better PCSM at 10 years with 18 months of ADT. Zoledronic acid did not impact PCSM. |
| D’Amico et al. [33,34,35] | 2004 2008 2015 |
Mostly IR HR |
RT alone RT + NA-CHT × 6 months |
206 | Prostate 70.35 Gy No pelvis |
RT alone had worse PCSM and OS in men with none/minimal cardiovascular disease at 16.6 years. |
| RTOG 94-08 [36,37] |
2011 2022 |
HR 11% IR 54% LR 35% |
RT Alone RT + NA-CHT × 4 months |
1979 | Pelvis 46.8 Gy Prostate 66.6 Gy |
RT + ADT improved OS in IR but not in LR. The OS curves converge at approximately 15 years. |
| EORTC 22991 [38,39] | 2016 2021 |
HR 24.8% IR 74.8% LR 0.4% |
DE-RT alone DE-RT + C-AHT × 6 months |
819 | If N+ risk 15% or >: Pelvis 46 Gy Prostate 70, 74, or 78 Gy |
RT + ADT improved EFS and DFS, but not OS nor DM at 10 years |
| PCS III [40] | 2020 | IR | RT + NA-CHT × 6 months DE-RT + NA-CHT × 6 months DE-RT alone |
600 | Prostate 70 Gy or 76 Gy No Pelvis |
RT + ADT improved BF, PFS, and PCSM compared to RT alone. No difference between 70 and 76 Gy + ADT. |
| TAP 32 [41,42] | 2012 2020 |
HR | ADT alone × 3 years ADT × 3 years + RT |
263 | Pelvis 46 Gy +/− 2 Gy Prostate 68–70 Gy +/− 2–4 Gy |
ADT + RT improved PCSM at 8 years |
| RTOG 0815 (Abstract) [43] | 2021 | IR | DE-RT alone DE-RT + TAS × 6 months |
1538 | Not reported | RT + TAS did not improve OS but had better MFS, PCSM, and bRFS |
| PR.3/MRC PR07 [44,45] | 2011 2015 |
HR | Life-long ADT alone Life-long ADT + RT |
1205 | Pelvis 45 Gy Prostate 65–69 Gy |
ADT + RT reduced the risk of death at 10 years. |
| Ito et al. [46] | 2020 | HR | RT + NA-C-AHT × 5 years RT + NA-C-AHT × 14 months + iADT thereafter up to year 5 |
303 | Prostate 72 Gy No pelvis |
No difference in bRFS, but non-inferiority was not demonstrated for the iADT arm |
| SPCG7 [47,48] | 2009 2016 |
Mainly HR | TAS × 3 months + Adjuvant Flutamide until death or progression TAS × 3 months + RT + Adjuvant Flutamide until death or progression |
875 | Prostate 70 Gy No pelvis |
RT + ADT improved PCSM and OS at 15 years. |
N+ = node-positive, PAo = Para-Aortic, LC = Local Control, MFS = Metastasis Free Survival, HT = Hormone therapy, BF = Biochemical Failure, DM = Distant Metastasis, PCSM = Prostate Cancer-Specific Mortality, DFS = Disease-Free Survival, CV = Cardiovascular, LR = Low Risk, CSS = Cancer-Specific Survival, DE-RT = Dose-Escalated RT, NSS = Non-statistically significant, UIR = Unfavorable Intermediate Risk, EBRT = External Beam Radiotherapy, HDRB = High Dose Rate Brachytherapy, EQD2 = Equivalent Dose in 2-Gy fractions, PFS = Progression-Free Survival, TAS = Total Androgen Suppression, iADT = Intermittent Androgen Deprivation Therapy, bRFS = Biochemical Recurrence Free Survival.