Background
Phase III, multi-arm multi-stage (MAMS) platform trial (STAMPEDE). 2061 patients with newly diagnosed metastatic prostate cancer (M1) starting long-term ADT (with or without docetaxel). Radiotherapy to the prostate was added to systemic therapy to test local consolidation in the oligometastatic-to-polymetastatic spectrum. Low metastatic burden defined as <4 bone metastases and no visceral metastases.
Interventions and follow up
Arm A: Radiotherapy (RT) to prostate (55 Gy in 20 fractions or 36 Gy in 6 fractions) + standard systemic therapy (ADT ± docetaxel)
Arm B: Standard systemic therapy (ADT ± docetaxel) alone
Primary endpoint: Failure-free survival (FFS)
mFollow up: 37 mo
Arm B: Standard systemic therapy (ADT ± docetaxel) alone
Primary endpoint: Failure-free survival (FFS)
mFollow up: 37 mo
Results
FFS (overall): HR 0.92 — not significant (P=.266)
FFS (low metastatic burden): HR 0.47, P<.001
FFS (high metastatic burden): HR 1.10 — no benefit
OS (low metastatic burden, 4-yr): 73% vs 61%, HR 0.68, P=.008
FFS (low metastatic burden): HR 0.47, P<.001
FFS (high metastatic burden): HR 1.10 — no benefit
OS (low metastatic burden, 4-yr): 73% vs 61%, HR 0.68, P=.008
Adverse events
Overall: Prostate RT generally well tolerated; no significant increase in grade ≥3 AEs overall
Gastrointestinal: Grade ≥2 bowel toxicity 5.3% vs 1.3%
Genitourinary: Grade ≥2 urinary toxicity 35.3% vs 26.7%; bowel and urinary effects consistent with pelvic radiation
Gastrointestinal: Grade ≥2 bowel toxicity 5.3% vs 1.3%
Genitourinary: Grade ≥2 urinary toxicity 35.3% vs 26.7%; bowel and urinary effects consistent with pelvic radiation
Conclusions
Prostate radiotherapy added to systemic therapy did not improve FFS in the overall M1 population, but demonstrated significant FFS and OS benefit in patients with low metastatic burden (<4 bone metastases, no visceral mets). This subgroup analysis established local consolidation RT as a standard approach in low-volume de novo mHSPC.
Key Limitations
Key Limitations: The OS benefit in low-burden disease was a subgroup finding — the overall trial was negative for FFS. Low versus high metastatic burden was defined by conventional imaging without PSMA PET; some low-burden patients may have had higher true disease burden by PSMA PET, potentially diluting the effect. The PSMA PET era may redefine which patients are truly low-volume. The optimal RT dose and fractionation schedule, extent of nodal irradiation, and integration with modern ARPI-based systemic therapy remain open questions.
Clinical Context
STAMPEDE-RT provided the definitive evidence supporting prostate-directed RT in low-volume de novo mHSPC, now a guideline recommendation (ESMO, EAU). For high-volume M1 disease, prostate RT provides no benefit. The PEACE-1 trial (abi + doce + RT ± prostate RT) and ongoing trials are evaluating RT in the context of intensified systemic therapy. PSMA PET-defined oligometastatic disease is increasingly used to select patients for prostate RT.
References
References: Parker CC et al, Lancet 2018