Circulating Tumor Cell Counts Associated with Prognosis and Response in Men Receiving Second-line Treatment for Metastatic Castration-resistant Prostate Cancer

IN THE OPEN-LABEL, phase 4 CARD trial, cabazitaxel, a semi-synthetic analog of docetaxel, was established as second-line therapy for men with metastatic castration-resistant prostate cancer (mCRPC) who had disease progression while receiving docetaxel and an androgen-signaling inhibitor (abiraterone or enzalutamide).

In a pre-planned analysis, Dr. Johann S. de Bono (The Royal Marsden Hospital and The Institute of Cancer Research, London, UK) and co-investigators presented data during the 2021 ASCO Genitourinary Cancers Symposium on circulating tumor cells (CTCs, defined as any cytokeratin-positive, CD45-negative cells) measured in the blood samples of men enrolled in the CARD trial at screening and at cycle 2 of therapy. They found that high baseline CTC counts were associated with lower survival, while a reduction in CTC counts during therapy was associated with improved progression-free survival.

Of the 255 patients enrolled, a total of 237 (92.9%) men at screening and 213 (83.5%) at cycle 2 had evaluable samples. Over 80% of patients had detectable CTCs ³ 1 at both time points in time (median 4.1 at screening and 5.2 at cycle 2), and the number of CTCs correlated with other serum measurements, including lactate dehydrogenase, alkaline phosphatase, and prostate-specific antigen. Notably, a reduction from a high to low category of CTCs correlated with objective tumor response. The findings suggest CTCs may have prognostic value for patients with mCRPC both at baseline and following changes during therapy, Dr. de Bono and his colleagues concluded. They are also carrying out additional analyses of the associations of CTC androgen receptor variant 7, chromosomal instability, heterogeneity status, single-cell genotypes, and the presence of CTCs with small-cell/neuroendocrine morphology.

Hiten D. Patel, MD, MPH, completed residency training in urologic surgery at the James Buchanan Brady Urological Institute and is currently a Clinical Instructor and Fellow in Urologic Oncology at Loyola University Medical Center. He has published studies related to epidemiology, comparative effectiveness, evidence-based reviews, and clinical trials in urologic oncology and related fields.

Bibliography:

de Bono JS, Pantel K, Efstathiou E, et al. CTC counts as a biomarker of prognosis and response in metastatic castration-resistant prostate cancer (mCRPC) from the CARD trial. J Clin Oncol. 2021;39 (6, suppl):41. Abstract 161. doi: 10.1200/JCO.2021.39.6_suppl.161

de Wit R, de Bono J, Sternberg CN, et al; CARD Investigators. Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. N Engl J Med. 2019;381(26):2506-2518. doi: 10.1056/NEJMoa1911206