Background
Phase III RCT (German ARO 96-02/AUO AP 09/95). 388 patients with pT3 pN0 prostate cancer after radical prostatectomy. The ITT2 population (undetectable PSA after RP) comprised 159 wait-and-see and 148 adjuvant RT patients. Median follow-up ~111 months.
Interventions and follow up
Arm A: Adjuvant radiotherapy 60 Gy 3D-conformal to the surgical bed
Arm B: Wait-and-see (observation)
Primary endpoint: Progression-free survival (biochemical recurrence, clinical recurrence, or death)
mFollow up: 111 months (ART), 113 months (WS)
Arm B: Wait-and-see (observation)
Primary endpoint: Progression-free survival (biochemical recurrence, clinical recurrence, or death)
mFollow up: 111 months (ART), 113 months (WS)
Results
PFS at 10 years: 56% (ART) vs 35% (WS), P<.0001
PFS in pT3b patients: WS rate 28%
PFS in R1 patients: WS rate 27%
Metastasis-free survival: Not significantly improved (underpowered)
OS: Not significantly improved (underpowered)
PFS in pT3b patients: WS rate 28%
PFS in R1 patients: WS rate 27%
Metastasis-free survival: Not significantly improved (underpowered)
OS: Not significantly improved (underpowered)
Adverse events
Main adverse events: Late grade 3 bladder toxicity: 1 patient (ART). Late grade 2 bladder toxicity: 3 patients. Late grade 2 rectum toxicity: 2 patients. No grade 4 events.
Conclusions
Adjuvant radiotherapy reduced the risk of biochemical or clinical progression by approximately half (HR ~0.51) in pT3 prostate cancer at 10-year follow-up, with an excellent late toxicity profile. No significant benefit in metastasis-free survival or OS was demonstrated, likely due to inadequate statistical power.
Key Limitations
Key Limitations: Trial underpowered for OS and metastasis-free survival. ITT2 population (not full ITT) used as primary analysis, limiting generalizability. 60 Gy dose is lower than currently recommended salvage doses (66–70 Gy). The wait-and-see arm received salvage RT at progression, blurring the adjuvant vs. salvage distinction.
Clinical Context
ARO 96-02 is one of three trials supporting adjuvant RT in pT3 prostate cancer, alongside SWOG 8794 and EORTC 22911. Subgroup analyses suggest greatest benefit in pT3b and R1 patients. As with SWOG 8794, the subsequent RAVES and RADICALS-RT trials challenged the adjuvant approach, supporting early salvage RT instead.
References
References: Wiegel T et al, Eur Urol 2014 (10-yr follow-up)