ArticleJournal of the National Cancer Institute2024
Molecular features of prostate cancer after neoadjuvant therapy in the phase 3 CALGB 90203 trial.
Article in Journal of the National Cancer Institute, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 9 citations in OpenAlex.
- Sparse-Input Neural Network using Group Concave Regularization.Transactions on machine learning research · 2025Article
- Validation of a Digital Pathology-Based Multimodal Artificial Intelligence Biomarker in a Prospective, Real-World Prostate Cancer Cohort Treated with Prostatectomy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Computational analysis of treatment resistant cancer cells.Frontiers in cell and developmental biology · 2025Article
- Defining biology and recurrence risk in prostate cancers treated by neoadjuvant chemohormonal therapy.Journal of the National Cancer Institute · 2024Article
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundThe phase 3 CALGB 90203 (Alliance) trial evaluated neoadjuvant chemohormonal therapy for high-risk localized prostate cancer before radical prostatectomy. We dissected the molecular features of post-treated tumors with long-term clinical outcomes to explore mechanisms of response and resistance to chemohormonal therapy.
methodsWe evaluated 471 radical prostatectomy tumors, including 294 samples from 166 patients treated with 6 cycles of docetaxel plus androgen deprivation therapy before radical prostatectomy and 177 samples from 97 patients in the control arm (radical prostatectomy alone). Targeted DNA sequencing and RNA expression of tumor foci and adjacent noncancer regions were analyzed in conjunction with pathologic changes and clinical outcomes.
resultsTumor fraction estimated from DNA sequencing was significantly lower in post-treated tumor tissues after chemohormonal therapy compared with controls. Higher tumor fraction after chemohormonal therapy was associated with aggressive pathologic features and poor outcomes, including prostate-specific antigen-progression-free survival. SPOP alterations were infrequently detected after chemohormonal therapy, while TP53 alterations were enriched and associated with shorter overall survival. Residual tumor fraction after chemohormonal therapy was linked to higher expression of androgen receptor-regulated genes, cell cycle genes, and neuroendocrine genes, suggesting persistent populations of active prostate cancer cells. Supervised clustering of post-treated high-tumor-fraction tissues identified a group of patients with elevated cell cycle-related gene expression and poor clinical outcomes.
conclusionsDistinct recurrent prostate cancer genomic and transcriptomic features are observed after exposure to docetaxel and androgen deprivation therapy. Tumor fraction assessed by DNA sequencing quantifies pathologic response and could be a useful trial endpoint or prognostic biomarker. TP53 alterations and high cell cycle transcriptomic activity are linked to aggressive residual disease, despite potent chemohormonal therapy.
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