Tumor Transcriptome-Wide Expression Classifiers Predict Treatment Sensitivity in Advanced Prostate Cancers

Advanced prostate cancers respond to hormone therapy, but outcomes vary , and no predictive tests exist for informed treatment selection. To identify novel biomarker-treatment pairings, researchers examined the associations between biological pathways and 14- year survival outcomes of patients randomized to phase 3 trials testing docetaxel [chemotherapy] or abiraterone [hormone] treatment. They included transcriptome-wide RNA expression signatures and immunohistochemistry markers for Ki- 67 and PTEN in prostate tumors from 1,523 patients, of whom 832 were metastatic.

In summary, the key findings were:

1. Tumors with high proliferation rates or low androgen-receptor activity were linked to shorter patient survival.

2. The Decipher classifier was prognostic for outcome and also predicted tumor sensitivity to docetaxel chemotherapy .

3. Patients whose tumors showed PTEN inactivation had shorter survival, but their tumors were responsive to docetaxel.

Thus, this large-scale analysis of the phase-3 clinical trial of tumor RNA expression samples revealed novel biomarker treatment pairings to guide therapy choices in patients with metastatic prostate cancer. Transcriptome classifiers can predict docetaxel benefit and could be clinically implemented to improve patient management.

https://doi.org/10.1016/j.cell.2025.07.042