Prostate Cancer · Radiation · Localized · Intermediate-Risk Intensification · 2026-09-18

RTOG 9408

In localized prostate cancer treated with definitive RT, does adding 4 months of androgen-deprivation therapy improve cancer outcomes?

Population

Men with localized T1b–T2b prostate cancer and PSA ≤20 ng/mL; benefit was concentrated in intermediate-risk disease.

Intervention

4 months of flutamide plus an LHRH agonist with 66.6 Gy RT.

Comparator

RT alone.

Sample size / primary endpoint

1,979 randomized men in the long-term report; Overall survival; secondary disease-specific mortality, biochemical failure and metastasis

Absolute Effect

Primary efficacy result

18-year disease-specific mortality: 8% vs 14% (−6 percentage points)

Median follow-up 14.8 years among survivors.

18-year OS was 23% in both groups after late convergence; restricted mean survival time at 18 years was 11.8 vs 11.3 years (P=.05).

Biochemical failure, distant metastasis and disease-specific mortality favored combined therapy, particularly in intermediate-risk patients.

NNT / NNH

NNT: 17, based on 18-year disease-specific mortality.

NNH: not quantifiable for a single principal severe-toxicity endpoint; late grade ≥3 GU toxicity was 8% vs 5%.

Treatment burden and toxicity

Late grade ≥3 GI toxicity was 3% vs 2% and GU toxicity 8% vs 5% with RT plus ADT versus RT alone. Hormonal toxicity was also clinically relevant.

Quality of life: The benefit came with the expected short-term androgen-deprivation burden; the trial was not designed around modern validated QoL instruments.

Subgroups / clinically important modifiers

Long-term analyses show the clearest survival benefit in intermediate-risk disease, with little evidence of benefit in low-risk disease.

Limitations and maturity

RT dose and imaging were from an older era. Modern dose-escalated RT and contemporary systemic intensification may change the absolute balance.

Clinical interpretation

Four months of ADT with definitive RT improves disease-specific outcomes in appropriately selected localized prostate cancer, particularly intermediate-risk disease, but does not produce a persistent overall-survival advantage at very long follow-up.

RTOG 9408 is a foundational demonstration that modest systemic intensification can improve disease control when added to definitive prostate RT.

Primary / authoritative sources

RTOG 9408 long-term update (PubMed)

Original NEJM report (PubMed)