Non-invasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumor Cells.

PSA testing results in unnecessary biopsy and over-diagnosis with consequent over-treatment. Tissue biopsy is an invasive procedure, associated with significant morbidity. More accurate non- or minimum-invasive diagnostic approaches should be developed to avoid unnecessary prostate biopsy and over-diagnosis. We investigated the potential of using circulating tumor cell analysis in cancer diagnosis, particularly in predicting clinically significant prostate cancer in pre-biopsy patients.

We enrolled 155 treatment naïve prostate cancer patients and 98 pre-biopsy patients for circulating tumor cell numeration. RNA was extracted from circulating tumor cells from 184 patients for gene expression analysis. Kruskal-Wallis, Spearman's rank, multivariate logistic regression and random forest were applied to assess the association of circulating tumor cells with aggressive prostate cancer.

In localized prostate cancer patients, 54% were scored as circulating tumor cell positive, which was associated with higher Gleason score (p=0.0003), risk group (p<0.0001) and clinically significant prostate cancer (p<0.0001). In pre-biopsy group, positive circulating tumor cell score in combination with PSA predicted clinically significant prostate cancer with AUC=0.869. A 12-gene panel prognostic for clinically significant prostate cancer was also identified. Combining PSA level, circulating tumor cell-score and the 12-gene panel, AUC for clinically significant prostate cancer prediction was 0.927 and in cases with multi-parametric MRI data, adding these to multi-parametric MRI significantly increased the prediction accuracy (AUC 0.936 vs 0.629).

Circulating tumor cell analysis has the potential to significantly improve patient stratification by PSA and/or multi-parametric MRI for biopsy and treatment.

The Journal of urology. 2019 Aug 07 [Epub ahead of print]

Lei Xu, Xueying Mao, Alistair Grey, Glenda Scandura, Tianyu Guo, Edwina Burke, Jacek Marzec, Semah Abdu, Elzbieta Stankiewicz, Caitlin R Davies, Prabhakar Rajan, Karen Tipples, John Hines, Pui Ying Chan, Diane Campbell, Karen Wilkinson, Sakunthala Kudahetti, Jonathan Shamash, Tim Oliver, Daniel Berney, Greg Shaw, Yong-Jie Lu

Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK., Department of Urology, Barts Health NHS, London, UK., Department of Medical Oncology, Barts Health NHS, London, UK.