Improved Androgen Receptor Splice Variant 7 Detection Using a Highly Sensitive Assay to Predict Resistance to Abiraterone or Enzalutamide in Metastatic Prostate Cancer Patients.

In metastatic castration-resistant prostate cancer (mCRPC), androgen receptor splice variant 7 (AR-V7) expression is associated with a low response to androgen receptor signaling (ARS) inhibitors such as abiraterone or enzalutamide.

To perform a highly sensitive assay for detecting AR-V7 (hsAR-V7) in circulating tumor cells (CTCs) and evaluate its ability to predict response to ARS inhibitors.

From 41 mCRPC patients, CTCs were prospectively enriched using AdnaTest platform and analyzed for AR-V7 with and without the highly sensitive assay.

The first objective of the study was to compare AR-V7 detection rates with and without the highly sensitive assay. Next, we investigated how AR-V7 (detected without the highly sensitive assay) and hsAR-V7 status influenced prostate-specific antigen (PSA) response and long-term clinical outcomes (PSA progression-free survival [PFS] and radiological PFS) after ARS-inhibitor treatment. Finally, discriminatory abilities of the assays were assessed by C-index to compare their impact on long-term clinical outcomes.

AR-V7 detection rates increased from 22% to 56% when the highly sensitive assay was used. The discriminatory abilities of hsAR-V7 for PSA PFS (C-index, 0.74; 95% confidence interval [CI], 0.60-0.88) and radiological PFS (0.70; 95% CI, 0.55-0.85) were higher than those of AR-V7 detected without the highly sensitive assay (0.60, 0.51-0.72, and 0.56, 0.44-0.67, respectively). After ARS-inhibitor treatment, PSA response was lower in hsAR-V7+ (53%) than in hsAR-V7- (93%) patients (p = 0.016). AR-V7+ patients had shorter median PSA PFS (3.0 vs 10.6 mo, p = 0.032) and nonsignificantly shorter median radiological PFS (6.0 vs 14.8 mo, p = 0.24) compared with AR-V7- patients. The hsAR-V7+ status was associated with shorter median PSA PFS (3.0 mo vs not reached, p = 0.0001) and radiological PFS (median, 6.0 mo vs not reached, p = 0.0026).

The hsAR-V7 assay achieved the highest AR-V7 detection rates among those reported in mCRPC. Discriminatory abilities for long-term clinical outcomes were better with hsAR-V7 assay.

We prospectively analyzed circulating tumor cells from men with metastatic castration-resistant prostate cancer for androgen receptor splice variant 7 (AR-V7) status using a highly sensitive assay. It yielded higher AR-V7 detection rates and predicted resistance to androgen receptor signaling inhibitors with better discriminatory abilities for long-term clinical outcomes.

European urology oncology. 2019 Oct 29 [Epub ahead of print]

Denis Maillet, Nathalie Allioli, Julien Peron, Adriana Plesa, Myriam Decaussin-Petrucci, Sophie Tartas, Alain Ruffion, Sébatien Crouzet, Ruth Rimokh, Pierre-Germain Gillet, Gilles Freyer, Virginie Vlaeminck-Guillem

Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France; Centre de Recherche en Cancérologie de Lyon, INSERM 1052 CNRS UMR 5286, Centre Léon Berard, Université Claude Bernard Lyon 1, Lyon, France; Centre d'études, de Recherche et de Valorisation en Oncologie (CERVO), Faculté de Médecine et de Maïeutique Lyon Sud-Charles Mérieux, Pierre-Bénite, France. Electronic address: ., Centre de Recherche en Cancérologie de Lyon, INSERM 1052 CNRS UMR 5286, Centre Léon Berard, Université Claude Bernard Lyon 1, Lyon, France; Centre d'études, de Recherche et de Valorisation en Oncologie (CERVO), Faculté de Médecine et de Maïeutique Lyon Sud-Charles Mérieux, Pierre-Bénite, France; Institut des Sciences Pharmaceutiques et Biologiques, Faculté de Pharmacie, Université Claude Bernard Lyon 1, Lyon, France., Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France; Service de Biostatistique et Bioinformatique, Hospices Civils de Lyon, Lyon, France; Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, CNRS UMR 5558, Université Claude Bernard Lyon 1, Villeurbanne, France., Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France; Service d'Hématologie Biologique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France., Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France; Centre de Recherche en Cancérologie de Lyon, INSERM 1052 CNRS UMR 5286, Centre Léon Berard, Université Claude Bernard Lyon 1, Lyon, France; Faculté de Médecine et de Maïeutique Lyon-Sud-Charles Mérieux, Université Claude Bernard Lyon 1, Pierre-Bénite, France; Service d'Anatomie et de Cytologie Pathologiques, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France., Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France., Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France; Centre de Recherche en Cancérologie de Lyon, INSERM 1052 CNRS UMR 5286, Centre Léon Berard, Université Claude Bernard Lyon 1, Lyon, France; Centre d'études, de Recherche et de Valorisation en Oncologie (CERVO), Faculté de Médecine et de Maïeutique Lyon Sud-Charles Mérieux, Pierre-Bénite, France; Faculté de Médecine et de Maïeutique Lyon-Sud-Charles Mérieux, Université Claude Bernard Lyon 1, Pierre-Bénite, France; Service d'Urologie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France., Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France; Service d'Urologie, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France; Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, Lyon, France., Centre de Recherche en Cancérologie de Lyon, INSERM 1052 CNRS UMR 5286, Centre Léon Berard, Université Claude Bernard Lyon 1, Lyon, France., Centre de Recherche en Cancérologie de Lyon, INSERM 1052 CNRS UMR 5286, Centre Léon Berard, Université Claude Bernard Lyon 1, Lyon, France; Centre d'études, de Recherche et de Valorisation en Oncologie (CERVO), Faculté de Médecine et de Maïeutique Lyon Sud-Charles Mérieux, Pierre-Bénite, France; Faculté de Médecine et de Maïeutique Lyon-Sud-Charles Mérieux, Université Claude Bernard Lyon 1, Pierre-Bénite, France; Service d'Anatomie et de Cytologie Pathologiques, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France., Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France; Faculté de Médecine et de Maïeutique Lyon-Sud-Charles Mérieux, Université Claude Bernard Lyon 1, Pierre-Bénite, France., Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France; Centre de Recherche en Cancérologie de Lyon, INSERM 1052 CNRS UMR 5286, Centre Léon Berard, Université Claude Bernard Lyon 1, Lyon, France; Centre d'études, de Recherche et de Valorisation en Oncologie (CERVO), Faculté de Médecine et de Maïeutique Lyon Sud-Charles Mérieux, Pierre-Bénite, France; Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, Lyon, France; Service de Biochimie Biologie Moléculaire Sud, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France. Electronic address: .