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WNT pathway mutations in metachronous oligometastatic castration-sensitive prostate cancer - ScienceDirect

WNT pathway mutations in metachronous oligometastatic castration-sensitive prostate cancer - ScienceDirect

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WNT pathway mutations in metachronous oligometastatic castration-sensitive prostate cancer

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Outline

  1. Abstract
  2. Introduction
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. References
  8. Appendix. Supplementary materials

Figures (3)

  1. Figure 1. Frequency of metastatic lesion location at time of oligometastsis stratified by…

  2. Figure 2. Kaplan Meier survival curves of (a) overall survival and (b) radiographic…

  3. Figure 3. Kaplan Meier survival curves of overall survival stratified by WNT pathway…

Tables (3)


  1. Table 3

Elsevier

International Journal of Radiation Oncology*Biology*Physics

Abstract

Background

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

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's χ2 and Mann-Whitney U were used to determine differences in clinical factors between genomic strata. Kaplan-Meier survival curves were generated for radiographic progression-free survival (rPFS) and overall survival (OS), 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<0.01) and less likely to have regional lymph node metastases (29.0% vs 50.4%; p=0.02). 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 following metastatic diagnosis). Multivariable cox regression demonstrated WNT pathway mutations associated with significantly worse OS (HR=3.87, 95%CI 1.25-12.00).

Conclusion

Somatic WNT pathway alterations are present in approximately 11% of patients with omCSPC and are associated with an increased likelihood of visceral metastases. While these patients have a worse natural history, they may benefit from MDT.

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