By Lila Rouland | Published on November 10, 2025 | 3 min readMetastatic
hormone-sensitive prostate cancer (mHSPC) is a clinical entity in which
combination therapies have significantly improved overall survival. However,
despite these advances, interindividual variability in treatment response
remains high, making it difficult to identify patients at high risk of
progression.
Given this
heterogeneity,
circulating tumor cells (CTCs) are emerging as
non-invasive
blood biomarkers potentially predictive of clinical outcomes. While already
validated in castration-resistant prostate cancer (mCRPC), their prognostic
value in hormone-sensitive disease has yet to be established. This study aimed
to
assess the relationship between baseline CTC count and overall survival in
patients with mHSPC enrolled in the phase 3 S1216 clinical trial.
Can
circulating tumor cells predict survival in metastatic prostate cancer?
A
prospective design embedded in a multicenter trial
The study analyzed 503 baseline blood samples collected from participants in
the S1216 trial (N = 1313), who were randomized to receive standard hormonal
therapy (ADT + bicalutamide) or ADT + orteronel, a CYP17 inhibitor. CTCs were
quantified using the FDA-approved CellSearch platform and categorized into
three groups:
- 0
CTCs/7.5 mL
- 1–4
CTCs/7.5 mL
- ≥5
CTCs/7.5 mL
Clear
prognostic stratification based on survival outcomes
The results
revealed striking differences in median
overall survival (OS) according to
baseline CTC count:
- Not reached for patients with 0
CTCs
- 56.2
months for those with 1–4 CTCs
- 27.9
months for those with ≥5 CTCs
After
adjustment for clinical covariates (age, PSA level, bone metastases, etc.),
patients with ≥5 CTCs had a 3.22-fold higher risk of death (HR = 3.22;
95% CI: 2.22–4.68) and an increased risk of progression (HR = 2.46). The rate
of biochemical response (PSA ≤ 0.2 ng/mL at 7 months) was also significantly
lower in this group (OR = 0.26).
Strengthening
existing predictive tools
Adding the
CTC count to conventional prognostic factors (tumor volume, PSA, performance
status) improved 3-year survival prediction accuracy, with an AUC of 0.79
vs. 0.73 without CTCs. This improvement underscores their usefulness as a
complementary tool for risk stratification.
Toward
biomarker-guided personalized medicine
Baseline
CTC count in patients with mHSPC is
strongly correlated with overall survival,
disease progression, and biological response. It reflects the
aggressiveness of
the disease from diagnosis, independently of subsequent treatments.
This study
confirms that CTC count is a robust prognostic marker, outperforming
other clinical parameters. It could be used to:
- Identify high-risk patients
requiring intensified therapy (e.g., triplet therapy)
- Select
candidates for clinical trials
- Refine monitoring and follow-up
strategies
Limitations and future directions
- The biomarker analysis was
introduced after the trial began, limiting the dataset to a subgroup
(503/1313).
- The study did not differentiate
between synchronous and metachronous mHSPC.
- Although the experimental drug
(orteronel) did not improve OS, CTC count remained predictive regardless
of treatment.
In
conclusion, CTCs
pave the way for more personalized management of mHSPC, focusing on individual
tumor biology rather than solely on anatomical or clinical criteria.
Read next: Do vitamins protect against or promote prostate cancer? a matter of source and dosage
About the author – Lila RoulandDoctor of Oncology, specialized in Biotechnology and Management
