Does the circulating tumor cell count predict survival in metastatic hormone-sensitive prostate cancer?

By Lila Rouland | Published on November 10, 2025 | 3 min read


Metastatic 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.  

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