Increased choline uptake in androgen receptor (AR) copy number gain castration-resistant prostate cancers (CRPC)

Date

09 Oct 2016

Session

Poster display

Presenters

Vincenza Conteduca

Citation

Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372

Authors

V. Conteduca1, V. Casadio2, P. Caroli3, E. Scarpi1, C. Lolli1, C. Menna1, E. Bianchi4, G. Schepisi1, S. Testoni5, G. Gurioli2, S. Salvi2, D. Amadori1, G. Paganelli3, F. Matteucci3, G. Attard6, U. De Giorgi1

Author affiliations

  • 1 Medical Oncology, Istituto Tumori della Romagna I.R.S.T., 47014 - Meldola/IT
  • 2 Biosciences Laboratory, Istituto Tumori della Romagna I.R.S.T., 47014 - Meldola/IT
  • 3 Diagnostic Nuclear Medicine Unit, Istituto Tumori della Romagna I.R.S.T., 47014 - Meldola/IT
  • 4 Medical Oncology, Ospedale Infermi, 47923 - Rimini/IT
  • 5 Biostatistics And Clinical Trials, Istituto Tumori della Romagna I.R.S.T., 47014 - Meldola/IT
  • 6 Section Of Medicine, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, SH2 5NG - Sutton/GB
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Background

Preliminary data suggests an association between choline uptake and androgen receptor (AR) expression with upregulation of choline kinase alpha protein in prostate cancer. We aimed to make a direct comparison between circulating AR copy number variations (CNV) and 18F-fluorocholine (FCH) uptake on PET/CT in patients with metastatic CRPC.

Methods

We determined AR CNV by digital droplet PCR and Taqman on pre-treatment plasma from 80 patients with metastatic CRPC progressing after docetaxel treated with abiraterone (n = 47) or enzalutamide (n = 33) as we described previously (Romanel et al, Sci Transl Med 2015; Salvi et al, Br J Cancer 2015; Salvi et al, Oncotarget 2016). For all patients, an FCH PET/CT scans was performed at baseline and total lesion activity (TLA) and metabolic tumor volume (MTV) calculated. The primary end point was the correlation between circulating AR CNV and TLA and MTV. The secondary end points were progression-free survival (PFS) and overall survival (OS) stratified by circulating AR CNV and TLA/MTV.

Results

We observed AR copy number gain in 24 (30%) of 80 patients, 14 (30%) of 47 patients treated with abiraterone and 10 (29%) of 33 treated with enzalutamide. The number of metastatic lesions and previous therapeutic lines were higher in the enzalutamide group (P = 0.03 and P = 0.02, respectively). We observed a significant correlation between AR gain and TLA and MTV values (P = 0.001 and P = 0.004, respectively; Rs >0.6). Multivariate analysis revealed that AR CNV and TLA value were associated with both shorter PFS (P 

Conclusions

Choline uptake is higher in AR gained cancers. This introduces the possibility of identifying this molecularly distinct group using non-invasive imaging and supports the hypothesis of increased choline uptake in cancers overexpressing AR.

Clinical trial identification

None

Legal entity responsible for the study

Ugo De Giorgi

Funding

IRST IRCCS

Disclosure

All authors have declared no conflicts of interest.

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