WNT Pathway Mutations in Metachronous Oligometastatic Castration-Sensitive Prostate Cancer.
Int J Radiat Oncol Biol Phys
; 115(5): 1095-1101, 2023 04 01.
Article
em En
| MEDLINE
| ID: mdl-36708787
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%; Pâ¯=â¯.02). At time of oligometastasis, these patients were treated with MDT alone (33.9%), MDTâ¯+â¯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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Via de Sinalização Wnt
Tipo de estudo:
Diagnostic_studies
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Observational_studies
/
Risk_factors_studies
Limite:
Humans
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Male
Idioma:
En
Revista:
Int J Radiat Oncol Biol Phys
Ano de publicação:
2023
Tipo de documento:
Article