Abstract
Purpose: WNT signaling is a cellular pathway that has been implicated in the development and progression of prostate cancer. Oligometastatic castration-sensitive prostate cancer (omCSPC) represents a unique state of disease in which metastasis-directed therapy (MDT) has demonstrated improvement in progression-free survival. Herein, we investigate the clinical implications of genomic alterations in the WNT signaling cascade in men with omCSPC. Methods and Materials: We performed an international multi-institutional retrospective study of 277 men with metachronous omCSPC who underwent targeted DNA sequencing of their primary/metastatic tumor. Patients were classified by presence or absence of pathogenic WNT pathway mutations (in the genes APC, RNF43, and CTNNB1). Pearson χ2 and Mann-Whitney U tests were used to determine differences in clinical factors between genomic strata. Kaplan-Meier survival curves were generated for radiographic progression-free survival and overall survival, stratified according to WNT pathway mutation status. Results: A pathogenic WNT pathway mutation was detected in 11.2% of patients. Patients with WNT pathway mutations were more likely to have visceral metastases (22.6% vs 2.8%; P < .01) and less likely to have regional lymph node metastases (29.0% vs 50.4%; P = .02). At time of oligometastasis, these patients were treated with MDT alone (33.9%), MDT + limited course of systemic therapy (20.6%), systemic therapy alone (22.4%), or observation (defined as no treatment for ≥6 months after metastatic diagnosis). Multivariable cox regression demonstrated WNT pathway mutations associated with significantly worse overall survival (hazard ratio, 3.87; 95% confidence interval, 1.25-12.00). Conclusions: Somatic WNT pathway alterations are present in approximately 11% of patients with omCSPC and are associated with an increased likelihood of visceral metastases. Although these patients have a worse natural history, they may benefit from MDT.
Original language | English (US) |
---|---|
Pages (from-to) | 1095-1101 |
Number of pages | 7 |
Journal | International Journal of Radiation Oncology Biology Physics |
Volume | 115 |
Issue number | 5 |
DOIs | |
State | Published - Apr 1 2023 |
Bibliographical note
Funding Information:P.T.T. was funded by an anonymous donor, Movember Foundation-Distinguished Gentlemen's Ride-Prostate Cancer Foundation, Babara's Fund, National Capitol Cancer Research Fund, and the National Institutes of Health/National Cancer Institute (U01CA212007, U01CA231776, and U54CA273956) and Department of Defense (W81XWH-21-1-0296), and the STOMP trial was supported by Kom op tegen Kanker, a Belgian nonprofit organization.
Publisher Copyright:
© 2022 Elsevier Inc.
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.