Liquid Biopsy Cell Diversity Could Indicate Poor Prostate Cancer Prognosis

Prostate cancer patients who have a more heterogeneous set of detectable circulating tumor cells (CTCs) are more likely to develop resistance to anti-androgen therapy, according to the results of a study presented at a presscast ahead of the 2016 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held January 7–9 in San Francisco (abstract 163).

Presenter Howard I. Scher, MD, a medical oncologist at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, and colleagues found that among prostate cancer patients treated with either enzalutamide or abiraterone, those who had a higher CTC heterogeneity score with CTCs that varied in appearance and genetically did not respond well to hormonal therapy. Those patients with a high CTC heterogeneity score had a shorter median progression-free survival (PFS; 5 months vs 17 months among those patients with a low heterogeneity score; hazard ratio [HR], 2.2; P = .00182). The high heterogeneity score patients also had a shorter median overall survival, 9 months, compared with a not yet reached median survival among patients with a low heterogeneity score (HR, 5.51; P < .0001).

Researchers have been investigating whether CTCs, derived from a patient’s blood sample, could be used as a liquid biopsy to identify distinctive features of these cells or use their abundance as predictive biomarkers for response to certain cancer therapies.

The current standard of care for patients with metastatic castration-resistant prostate cancer (CRPC) is either enzalutamide or abiraterone acetate, both of which target androgen receptor signaling, yet which patients are more susceptible to each treatment and the optimal sequencing is not clear.

“One proposed biomarker of sensitivity [to these agents] is tumor heterogeneity,” said Scher. The study authors proposed that the heterogeneity of the CTCs would be reflective of prostate tumor heterogeneity.

Scher and colleagues, including those at San Diego–based Epic Sciences, which developed the CTC analysis platform, tested 221 blood samples from 179 patients. One hundred fifty patients were about to begin either enzalutamide or abiraterone and 71 patients were about to begin a taxane-based chemotherapy regimen. The cells were analyzed for size, shape, and other phenotypic features. A subset of 350 CTCs were individually sequenced and analyzed for clonal status and to assess genomic heterogeneity, including copy number variation.

“Overall survival is considerably longer in the low vs the high heterogeneity groups [among those patients treated with androgen-targeted therapy]. The same difference is not apparent in [those patients treated] with a taxane-based therapy,” said Scher.

“We’ve always relied on a patient’s tumor to get genetic information but this can be incredibly complicated for a number of reasons,” said presscast moderator Sumanta Pal, MD, medical oncologist at City of Hope in Duarte, California. “[This study] links certain CTC characteristics to response or lack of response [among prostate cancer patients].”

Additional validation by the researchers is ongoing. A randomized clinical trial is still needed to assess the utility of this CTC test for metastatic CRPC patients.

The study was partly funded by the Prostate Cancer Foundation, MSKCC SPORE, and MSKCC Core Grant.