Baseline circulating tumor cell (CTC) count was found to be significantly prognostic of clinical outcome in a phase III trial of metastatic castration-sensitive prostate cancer (mCSPC). The results suggest that CTC count might be used as a noninvasive biomarker to help guide treatment decisions (Abstract 5506).
“CTC counts have been evaluated as a biomarker in prostate cancer for some time,” said Amir Goldkorn, MD, of the Keck School of Medicine and Norris Comprehensive Cancer Center at the University of Southern California, who presented the results during the ASCO20 Virtual Scientific Program. He noted that CTC counts have been well validated in several studies for use with metastatic castration-resistant prostate cancer, but the studies in mCSPC have been smaller, and they predate the current era of combination therapy in this setting.
The ongoing SWOG S1216 randomized trial is designed to compare androgen deprivation plus either bicalutamide or orteronel (TAK-700) in patients with mCSPC; data on the primary outcome of overall survival are expected in the next 12 to 18 months. CTC counts using the U.S. Food and Drug Administration–approved CELLSEARCH assay were included as part of the trial. The investigators collected 523 samples at baseline and 213 samples at the time of progression to castration-resistant disease.
There were 264 patients available for an analysis of 7-month prostate-specific antigen (PSA) response and 336 patients available for a 2-year progression-free survival (PFS) analysis. The researchers included an equal number of samples from each treatment arm for both of these analyses.
Compared to patients with a baseline CTC count of at least 5, those with a CTC count of 0 had an increased chance of achieving a PSA partial response at 7 months, with an odds ratio (OR) of 2.66 (p = 0.02; Figure). Compared to those with a CTC count of 1 to 4, the OR was not significant (p = 0.28).
The same was true for complete responses, where compared to patients with a count of 5 or greater, those with a CTC count of 0 had an OR of 6.06 (p ≤ 0.001). Again, the difference between undetectable CTCs and counts of 1 to 4 was not significantly different (p = 0.13).
In the PFS analysis, those with a CTC count of 1 to 4 were more likely than those with undetectable CTCs to have disease progression or to have died at 2 years, although this did not reach significance, with an OR of 1.74 (95% CI [0.99, 3.04]; p = 0.052).
Those with a CTC count of 5 or higher had further increased risk compared to those with a count of 0, with an OR of 3.72 (95% CI [1.71, 8.09]; p = 0.001). The OR for those with a CTC count of 5 to 9 was 2.44 (95% CI [0.69, 8.67]; p = 0.17), whereas for those with a count of 10 or higher it was 4.51 (95% CI [1.77, 11.5]; p = 0.002).
Using a CTC count of 5 as a cutoff point as well as comparing undetectable levels to a CTC count of 1 or higher also yielded significant differences. This was true in both cases for PSA partial and complete responses, as well as for PFS at 2 years.
“Based on these results, CTC count may be an effective noninvasive prognostic marker at presentation,” Dr. Goldkorn said, adding that it could help identify which men would benefit from hormone therapy and which might benefit from more aggressive therapy or early alternate interventions.
“Based on these results, CTC count may be an effective noninvasive prognostic marker at presentation.” – Dr. Amir Goldkorn
David R. Wise, MD, PhD, of Perlmutter Cancer Center at NYU Langone Health, was the discussant for the abstract. He said the authors should be congratulated for completing the largest prospective study to date on the prognostic significance of CTCs in hormone-sensitive prostate cancer.
Dr. Wise noted, though, that it is not yet clear whether CTC count can predict who will benefit from escalated therapy. “Further analysis of the TAK-700 study once the data mature will be an excellent opportunity to demonstrate the clinical utility of this biomarker,” he said.
— Dave Levitan
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