Table 1 Study demographics of included 19 studies.

SALV-ENZA Tran et al. [29]

RCT

RP

PSA ≥ 0.05 ng/ml GS8-10 GS7 with pT3 or R1

PSA ≥ 0.2 ng/ml

6 months

Enzalutamide (160 mg) + RT (66.6–70.2 Gy/37–39 fr)

Placebo+RT (66.6–70.2 Gy/37–39 fr)

NA

FORMULA 509 Nguyen et al. [34]

RCT

RP

PSA ≥ 0.1 ng/ml one or more unfavorable features (GS8-10, PSA > 0.5, pT3/T4, pN1 or radiographic N1, PSADT < 10 months, positive margins, persistent PSA, gross local/regional disease, or Decipher High Risk)

NA

6 months

Abiraterone (1000 mg) + predonisone (5 mg) + Apalutamide (240 mg) + ADT + RT ( ± PLNRT)

Bicalutamide (50 mg) + ADT + RT ( ± PLNRT)

NA

NRG Oncology/RTOG 0534 SPPORT Pollack et al. [37]

RCT

RP

PSA ≥ 0.1 ng/ml pT2/3 GS ≤ 9

PSA ≥ nadir + 2.0 ng/ml local failure metastasis death

ADT: 6 weeks

RT (64.8–70.2 Gy)

RT (64.8–70.2 Gy) + ADT

RT (19.8–25.2 Gy) + ADT + PLNRT (45 Gy)

RTOG 9601 Jackson et al. [54] Shipley et al. [41]

RCT

RP

PSA ≥ 0.2 ng/ml pT2 with positive margin/T3

PSA ≥ nadir + 0.3 ng/ml

2 years

Bicalutamide (150 mg) + RT (64.8 Gy/36 fr)

RT (64.8 Gy/36 fr)

NA

JCOG0401 Yokomizo et al. [24]

RCT

RP

PSA ≥ 0.4 ng/ml pT0/2/3 pN0/x

PSA rise if previous <0.4 ng/ml: ≥0.4 ng/ml PSA rise if previous >0.4 ng/ml: Any increase PSA at any point: >PSA at enrolment

Bicalutamide should be continued as long as it is effective

Bicalutamide (80 mg)

RT (64.8 Gy/36 fr) ± Bicalutamide (80 mg)

NA

GETUG-AFU 16 Carrie et al. [23, 42]

RCT

RP

PSA ≥ 0.2 ng/ml

PSA > nadir + 0.5 ng/ml

ADT: 6 months

RT (66 Gy/33 fr) + ADT

RT (66 Gy/33 fr)

NA

EMBARK Freedland et al. [31]

RCT

RP ± RT or RT

PSA ≥ 2 ng/ml (post-RT) PSA ≥ 1 ng/ml (post-RP) PSADT ≤ 9 months

PSADT ≤ 10 months

36 weeks

Enzalutamide(160 mg) + ADT

Enzalutamide (160 mg)

Placebo + ADT

PRESTO Aggarwal et al. [36]

RCT

RP ± RT

PSA ≥ 0.5 ng/ml PSADT ≤ 9 months

PSA rise to ≥25% PSA ≥ nadir + 2 ng/ml

52 weeks

Apalutamide (240 mg) + Abiraterone (1000 mg) + predonine (10 mg) + ADT

Apalutamide (240 mg) + ADT

ADT

NCT01790126 Aggarwal et al. [26]

RCT

RP ± RT or RT

PSA ≥ 1.0 ng/ml (post-RP) PSA ≥ nadir + 2.0 ng/ml (post-RT) PSADT ≤ 12 months

PSA rise to ≥50% PSA ≥ nadir + 2 ng/ml

12 months

Apalutamide (240 mg) + ADT

Apalutamide (240 mg)

ADT

NCT01786265 Spetsieris et al. [33]

RCT

RP ± RT or RT

PSA ≥ 0.2 ng/ml (post-RP) PSA ≥ nadir + 2.0 ng/ml (post-RT)

PSA ≥ 1.0 ng/ml

8 months

Abiraterone (1000 mg) + predonine (5 mg) + ADT

ADT

NA

NCT01751451 Autio et al. [28]

RCT

RP ± RT

PSA ≥ 1.0 ng/ml

PSA rise to ≥25%

8 months

Abiraterone (1000 mg) + predonine (10 mg) + ADT

Abiraterone (1000 mg) + predonine (10 mg)

ADT

TAX3503 Morris et al. [30]

RCT

RP ± RT

PSA ≥ 1.0 ng/ml PSADT ≤ 9 months

PSA ≥ 0.05 ng/ml

DOC: 10 cycles ADT: 18 months

Docetaxel (75 mg/m²) + ADT

ADT

NA

NCT00764166 Oudard et al. [35]

RCT

RP ± RT

PSA ≥ 0.2 ng/ml

PSA ≥ 0.2 ng/ml

DOC: 6 cycles ADT: 12 months

Docetaxel (70 mg/m²) + ADT

ADT

NA

TOAD Duchesne et al. [38]

RCT

RP ± RT or RT

PSA ≥ 0.2 ng/ml (post-RP) PSA ≥ nadir + 2.0 ng/ml (post-RT)

Radiological progression

NA

Delayed ADT

Immediate ADT

NA

NCT00928434 Crawford et al. [39]

RCT

RP or other primary therapy

PSA ≥ 0.2 ng/ml (post-RP) 3 separate PSA ≥ nadir PSA (post other primary therapy)

PSA progression additional PCa therapy death

T1: 7 months

Intermittent ADT

Continuous ADT

NA

NCIC Crook et al. [40]

RCT

RT

PSA ≥ 3.0 ng/ml (post RT)

NA

T1: 8 months

Intermittent ADT

Continuous ADT

NA

ARTS Schröder et al. [32]

RCT

RP ± RT, RT

PSA ≥ 0.4 ng/ml (post-RP) PSA ≥ 2.0 ng/ml (post-RT) PSADT 3–24 months cT1-T3aN0M0

PSADT ≤ 3 months PSA > 20 ng/ml (post-RT) PSA > 10 ng/ml (post-RP) PSA rise ≥50% pathological progression radiological progression

2 years

Dutasteride (0.5 mg)

Placebo

NA

PROTECT Beer et al. [27]

RCT

RP ± RT or ±ADT

Increase PSA PSA ≥ 3.0 ng/ml, 1.25 × nadia (previous ADT)

PSA ≥ 3.0 ng/ml

NA

Sipuleuce-T

Placebo

NA

Goluboff et al. [25]

RCT

RP ± RT or ADT

PSA ≥ 0.4 ng/ml PSA rise ≥10%

PSA progression

NA

Exisulind (250 mg × 2/day)

Placebo

NA