RTOG 94-08

Background

Phase III RCT (RTOG 94-08). 1,979 patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and PSA ≤20 ng/mL, enrolled 1994–2001. Randomized: RT alone (66.6 Gy/37 fx) vs RT + 4 months total androgen suppression (goserelin + flutamide, starting 2 months before RT and continuing through RT). This trial definitively established the benefit of short-term ADT in combination with radiotherapy for localized prostate cancer, particularly for intermediate-risk patients.

Interventions and follow up

Arm A: Radiotherapy alone: 66.6 Gy/37 fx
Arm B: Radiotherapy + 4 months ADT (goserelin 3.6 mg q4wk + flutamide 250 mg TID, starting 2 months before RT through end of RT)
Primary endpoint: Overall survival
mFollow up: Median 9.1 year

Results

10-year OS: 62% RT+ADT vs 57% RT alone, HR 1.17 (RT alone), P=.03 (absolute 5% benefit)
10-year disease-specific mortality: 4% RT+ADT vs 8% RT alone, HR 1.87, P=.001
10-year biochemical failure: Significantly improved with RT+ADT (P<.001)
By risk group: OS benefit concentrated in intermediate-risk (P=.002); no significant benefit in low-risk (P=.61)

Adverse events

Main adverse events: Grade 3+ hormone-related toxicity: <5% in RT+ADT arm. No significant difference in late radiation toxicity between arms. Hot flashes, erectile dysfunction common with ADT. No increased cardiovascular deaths with short-term ADT.

Conclusions

Short-term (4-month) ADT added to radiotherapy significantly improves overall survival and disease-specific mortality in patients with localized prostate cancer with a PSA ≤20 ng/mL. The benefit is driven primarily by intermediate-risk patients; low-risk patients do not derive significant benefit. This established short-term ADT + RT as standard of care for intermediate-risk prostate cancer.

Key Limitations

Key Limitations: RT dose (66.6 Gy) is below current standard (78 Gy), so the benefit of 4-month ADT at dose-escalated RT is less clear. Duration of ADT (4 months) is now recognized as potentially suboptimal for high-risk disease (where 18–36 months is standard). The trial predates IMRT and dose escalation; some benefit attributed to ADT may be partially offset by modern RT dose escalation. No subgroup analysis for high-risk patients.

Clinical Context

RTOG 94-08 is one of the landmark prostate ADT+RT trials alongside D'Amico (6 months ADT), EORTC 22863 (3 years ADT for high-risk), and RTOG 8610 (Shipley). Together, these trials established the standard: low-risk → RT alone; intermediate-risk → short-term ADT (4–6 months) + RT; high-risk → long-term ADT (18–36 months) + RT. Current NCCN guidelines recommend 4–6 months of ADT with RT for intermediate-risk and 18–36 months for high-risk prostate cancer.

References

References: Jones CU et al, N Engl J Med 2011 (RTOG 94-08)