TP53 Outperforms Other Androgen Receptor Biomarkers to Predict Abiraterone or Enzalutamide Outcome in Metastatic Castration-Resistant Prostate Cancer.
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De Laere Bram, Oeyen Steffi, Mayrhofer Markus, Whitington Tom, van Dam Pieter-Jan, Van Oyen Peter, Ghysel Christophe, Ampe Jozef, Ost Piet, Demey Wim, Hoekx Lucien, Schrijvers Dirk, Brouwers Barbara, Lybaert Willem, Everaert Els G, De Maeseneer Daan, Strijbos Michiel, Bols Alain, Fransis Karen, Beije Nick, de Kruijff Inge E, van Dam Valerie, Brouwer Anja, Goossens Dirk, Heyrman Lien, Van den Eynden Gert G, Rutten Annemie, Del Favero Jurgen, Rantalainen Mattias, Rajan Prabhakar, Sleijfer Stefan, Ullén Anders, Yachnin Jeffrey, Grönberg Henrik, Van Laere Steven J, Lindberg Johan, Dirix Luc Y
Аннотация
RESULTS: Overall, no single AR perturbation remained associated with adverse prognosis after multivariable analysis. Instead, tumor burden estimates (CTC counts, ctDNA fraction, and visceral metastases) were significantly associated with PFS. TP53 inactivation harbored independent prognostic value [HR 1.88; 95% confidence interval (CI), 1.18-3.00; P = 0.008], and outperformed ARV expression and detection of genomic AR alterations. Using Cox coefficient analysis of clinical parameters and TP53 status, we identified three prognostic groups with differing PFS estimates (median, 14.7 vs. 7.51 vs. 2.62 months; P < 0.0001), which was validated in an independent mCRPC cohort (n = 202) starting first-line ARSi (median, 14.3 vs. 6.39 vs. 2.23 months; P < 0.0001).
CONCLUSIONS: In an all-comer cohort, tumor burden estimates and TP53 outperform any AR perturbation to infer prognosis.See related commentary by Rebello et al., p. 1699.