External validation of the NADIR model for early prostate-specific antigen response prediction in enzalutamide-treated metastatic hormone-sensitive prostate cancer: An analysis of the ARCHES trial
In brief
NADIR model predicted early PSA response rates from 92% to 37% across groups
In an external validation of 558 enzalutamide-treated patients, 64% reached the target PSA level by 6 months, and response rates ranged from 92% in the highest predicted-probability group to 37% in the lowest. The model also separated patients by later mortality risk, but whether using its predictions to guide treatment improves outcomes remains untested.
- Journal
- Cancer (Q1)
- Published
- 1 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Soumyajit Roy, Andrew J Armstrong, Neeraj Agarwal, Rana R McKay, Angela Y Jia, Samuel Lichtman-Mikol, et al.
- PMID
- 42791604
- DOI
- 10.1002/cncr.70615
Why clinicians should know about it
- Picked for Radiation Oncology (top studies of the week, 27 September 2026): Prostate cancer PSA model, no radiation component
- Picked for Surgical Oncology (top studies of the week, 27 September 2026): High-quality evidence in a top journal
- Picked for Urology (top studies of the week, 27 September 2026): Early PSA response predicts overall survival in mHSPC
Abstract
BACKGROUND: Early favorable prostate-specific antigen (PSA) response to ≤0.2 ng/mL by 6 months is associated with superior overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC). The nadir androgen receptor pathway inhibitor (ARPI)-derived integrative response (NADIR) model is a multivariable model developed to predict this early favorable PSA response in patients receiving ARPI. The authors report an independent external validation of the locked NADIR model in the ARCHES trial. METHODS: Of 574 enzalutamide-treated patients, 558 with complete predictors were included. Discrimination, Brier score/index of prediction accuracy (IPA), and calibration were assessed. Predicted probability tertiles were used descriptively for PSA response. Six-month landmark Cox models explored associations with OS. A sensitivity analysis restricted the cohort to <3 months of prior androgen deprivation therapy (ADT). RESULTS: Early favorable PSA response occurred in 359 patients (64%). The area under the receiver operating characteristic curve was 0.80 (95% confidence interval [CI], 0.76-0.83), the Brier score was 0.17, and the IPA was 25%. Recalibration intercept was 0.026 and slope was 0.97. Response rates across decreasing predicted probability tertiles were 92%, 64%, and 37%. In the landmark analysis (n = 547; 177 deaths), each 10-percentage-point increase in predicted probability was associated with lower mortality (hazard ratio, 0.90; 95% CI, 0.85-0.96). In the <3-month prior-ADT subgroup (n = 401), the area under the receiver operating characteristic curve and IPA were 0.78 and 23%, respectively. CONCLUSIONS: The NADIR model demonstrates robust and reproducible discrimination, calibration, and prognostic stratification in a distinct ARPI-treated mHSPC cohort, supporting its potential utility for early response risk stratification and trial enrichment pending prospective validation of model-guided treatment adaptation.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.