Circulating tumor cell count may serve as a prognostic biomarker in mHSPC

Elevated circulating tumor cell (CTC) count at baseline was associated with poor response, rapid progression, and poor overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC), according to data recently published in JAMA Network Open.¹

The median PFS was 11.3 months for men with 5 or more CTCs per 7.5 mL, compared with 59.9 months for men with 0 CTCs per 7.5 mL.

According to the authors, these data indicate that CTC count may serve as a valuable prognostic biomarker at baseline in this patient population, especially when used in combination with existing prognostic factors.

“No one, until now, has looked at whether CTC counts can be used right at the beginning, when a man first presents with metastatic prostate cancer, to tell us whether he’s going to live a long or short time, or whether or not he will progress with therapies,” said lead author Amir Goldkorn, MD, in a news release on the findings.² Goldkorn is an associate director of translational sciences at the USC Norris Comprehensive Cancer Center and a professor of medicine at the Keck School of Medicine of USC.

Goldkorn continued, “You couldn’t tell these men apart when they walked through the door. All of their other variables and prognostic factors were seemingly the same, and yet they had very, very different outcomes over time.”

For the study, the investigators assessed peripheral blood samples from men with newly diagnosed mHSPC who were enrolled in the phase 3 S1216 trial. Patients in the S1216 study received androgen deprivation therapy (ADT) combined with either orteronel or bicalutamide.

In total, 1313 samples were obtained for the analysis. Of those, 503 samples were collected at baseline. Among all baseline samples, 60 (11.9%) contained 5 or more CTCs per 7.5 mL, 107 (21.3%) contained 1 to 4 CTCs per 7.5 mL, and 336 (66.8%) contained 0 CTCs per 7.5 mL.

Data showed that men with 5 or more CTCs per 7.5 mL at baseline had a lower likelihood of prostate-specific antigen (PSA) complete response (OR, 0.26; 95% CI, 0.12-0.54; P < .001) compared with men with no CTCs per 7.5 mL at baseline, even after adjusting for baseline clinical co-variates.

Specifically, in patients with 0 CTCs per 7.5 mL at baseline, a PSA complete response was achieved in 58.5% of patients who received ADT plus bicalutamide and 68.2% of patients who received ADT plus orteronel. Comparatively, in patients with 5 or more CTCs per 7.5 mL at baseline, a PSA complete response was achieved in 15.6% of patients in the ADT plus bicalutamide arm and 39.3% of patients in the ADT plus orteronel arm.

Men with 5 or more CTCs per 7.5 mL at baseline also had a significantly higher risk of death (HR, 3.22; 95% CI, 2.22-4.68; P < .001) and risk of disease progression (HR, 2.46; 95% CI, 1.76-3.43; P < .001) compared with men with lower CTC counts at baseline.

The median OS was 27.9 months (95% CI, 24.1-31.2 months) in men with 5 or more CTCs per 7.5 mL, compared with 56.2 months (95% CI, 45.7-69.8 months) in men with 1 to 4 CTCs per 7.5 mL and not reached (at 78.0 months of follow-up) in men with no CTCs per 7.5 mL. Similarly, the median progression-free survival (PFS) was 11.3 months (95% CI, 8.8-16.5 months) for men with 5 or more CTCs per 7.5 mL, compared with 20.7 months (95% CI, 15.1-32.9 months) for those with 1 to 4 CTCs per 7.5 mL and 59.9 months (95% CI, 49.4-83.7 months) for men with 0 CTCs per 7.5 mL.

The investigators also observed that the addition of baseline CTC count to other known prognostic factors improved the prognostic value for 3-year survival. With known covariates alone, the area under the curve was 0.73 (95% CI, 0.67-0.79), which increased to 0.79 with the addition of baseline CTC count (95% CI, 0.73-0.84).

Based on these findings, the team is now working to develop a blood test that measures the composition of CTCs and circulating tumor DNA with the goal of developing an enhanced predictive biomarker, according to the news release.²

Overall, the authors concluded, “Specifically, in men with newly diagnosed mHSPC, of whom two-thirds generally have good performance status and years of life expectancy, baseline CTC count may identify the one-third of men with more aggressive disease who are likely to experience worse outcomes. This prognostic ability may be of particular benefit in the slate of new clinical trials being launched to test standard mHSPC treatment vs intensified triple therapy (ADT, ARSI, chemotherapy) or other novel combinations.”¹

References

1. Goldkorn A, Tangen C, Plets M, et al. Circulating tumor cell count and overall survival in patients with metastatic hormone-sensitive prostate cancer. JAMA Netw Open. 2024;7(10):e2437871. doi:10.1001/jamanetworkopen.2024.37871

2. An early blood test can predict survival in patients with metastatic prostate cancer, shows USC study. News release. Keck School of Medicine of USC. October 7, 2024. Accessed October 8, 2024. https://keck.usc.edu/news/an-early-blood-test-can-predict-survival-in-patients-with-metastatic-prostate-cancer-shows-usc-study/