Background
Phase 3, double-blind, placebo-controlled RCT; N=2109; newly diagnosed high-risk localized or locally advanced prostate cancer, candidates for radical prostatectomy; randomized 1:1 to perioperative ADT+apalutamide vs ADT+placebo (6 cycles of 28 days before and after radical prostatectomy with pelvic lymph-node dissection).
Results
Interventions and follow up: Arm A: ADT + apalutamide 240 mg PO daily — 6 cycles neoadjuvant + 6 cycles adjuvant around radical prostatectomy (n=1057)
Arm B: ADT + placebo, same schedule (n=1052)
Primary endpoints (dual): pathological complete response or minimal residual disease (ypT2 or lower, tumor ≤5 mm); and metastasis-free survival (MFS)
mFollow up: 61.7 mo
Results: pCR or MRD: 8.9% vs 1.0%; OR 10.17 (95% CI 5.27–19.64); P<.001
MFS (5-yr): 78.2% vs 73.5%; HR 0.80 (95% CI 0.67–0.96); P=.02
EFS, time to first subsequent treatment, time to distant metastasis: all significantly favored apalutamide (P<.001 for each)
Arm B: ADT + placebo, same schedule (n=1052)
Primary endpoints (dual): pathological complete response or minimal residual disease (ypT2 or lower, tumor ≤5 mm); and metastasis-free survival (MFS)
mFollow up: 61.7 mo
Results: pCR or MRD: 8.9% vs 1.0%; OR 10.17 (95% CI 5.27–19.64); P<.001
MFS (5-yr): 78.2% vs 73.5%; HR 0.80 (95% CI 0.67–0.96); P=.02
EFS, time to first subsequent treatment, time to distant metastasis: all significantly favored apalutamide (P<.001 for each)
Adverse events
Grade 3/4 (any): 39.6% vs 31.0%
Main driver of excess: rash (apalutamide)
Main driver of excess: rash (apalutamide)
Conclusions
Perioperative ADT+apalutamide around radical prostatectomy significantly improved pathological response and metastasis-free survival vs ADT alone in high-risk localized/locally advanced prostate cancer — the first positive perioperative androgen-receptor-pathway-inhibitor intensification in this surgical setting. Presented at ASCO 2026.
Key Limitations
Absolute pCR/MRD rates low (8.9% vs 1.0%); MFS benefit modest (4.7% absolute at 5 yr); OS immature; surgically managed patients only (not generalizable to radiotherapy-managed disease); added toxicity (rash, ADT-related).
Clinical Context
Apalutamide (Erleada) is FDA/EMA-approved for non-metastatic CRPC (SPARTAN) and metastatic castration-sensitive disease (TITAN); it is not yet approved perioperatively for localized disease — these data are expected to support a regulatory submission. Prior practice for surgically managed high-risk localized disease was radical prostatectomy ± ADT without proven systemic intensification; the accompanying NEJM editorial anticipated rapid adoption as a new standard of care. Competing paradigm: radiotherapy + ADT + abiraterone (STAMPEDE) for high-risk/node-positive disease.