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High-purity CTC RNA sequencing identifies prognostic prostate cancer phenotypes by Marina Sharifi et al.

Marina Sharifi/medicine.wisc.edu

Feb 12, 2025, 09:24

High-purity CTC RNA sequencing identifies prognostic prostate cancer phenotypes by Marina Sharifi et al.

On February 06 2025, a paper by Marina Sharifi et al. was published in Cancer Discovery, titled:

“High-purity CTC RNA sequencing identifies prostate cancer lineage phenotypes prognostic for clinical outcomes”

Authors: Marina Sharifi, Jamie Sperger, Amy Taylor, Shuang Zhao, Joshua Lang et al.

The study used CTC RNA sequencing to classify metastatic prostate cancer into four phenotypes. Luminal B, with high AR signalling and proliferation, had poor survival and rapid progression on Lutetium-177–PSMA-617. This highlights CTC sequencing as a tool for tracking disease and the need for better treatments for aggressive cases.

Overall Survival (OS) Findings:

Luminal B and Neuroendocrine (NE) phenotypes had the worst OS.

Luminal B phenotype: Median OS = 6 months (Hazard Ratio [HR] = 9.1, 95% Confidence Interval [CI]: 3.8–21.8, p < 0.0001).
Neuroendocrine phenotype: Median OS = 3.7 months (HR = 11.8, 95% CI: 2.4–57.2, p = 0.0019).

Luminal A and Low Proliferation phenotypes had better OS:

Luminal A phenotype: Median OS = 13 months (HR = 2.0, 95% CI: 0.7–6.2).
Low Proliferation phenotype: Median OS = 11.8 months (HR = 2.2, 95% CI: 0.6–8.1).
Low CTC burden patients had the best survival, with OS not reached.

In multivariate analysis, factors associated with worse OS included:

Presence of metastatic castration-resistant prostate cancer (mCRPC) or neuroendocrine prostate cancer (NEPC).
Higher PSA levels.
Visceral metastases.
Luminal B and NE CTC phenotypes (both were independent predictors of poor OS).

Progression-Free Survival (PFS) Findings (Specific to 177Lu-PSMA-617 Therapy):

Patients with the Luminal B phenotype had significantly shorter radiographic PFS when treated with 177Lu-PSMA-617:

Luminal B median PFS: 3.5 months vs. 11.7 months in other phenotypes (p < 0.005).

Early progression (within 18 weeks of starting 177Lu-PSMA-617) was significantly more common in the Luminal B phenotype compared to other CTC phenotypes (p = 0.033).

Key Takeaway:

The Luminal B phenotype is associated with aggressive disease, poor OS, and early progression on 177Lu-PSMA-617, highlighting the need for alternative treatment strategies for these patients.

Read more posts about Prostate Cancer on oncodaily.com.