Abstract
Background
The site of prostate cancer metastasis is an important predictor of oncologic outcomes, however, the clinicogenomic characteristics associated with the site are not well-defined. Herein, we characterize the genomic alterations associated with the metastatic site of prostate cancer.
Methods
We analyzed clinical and genomic data from prostate cancer patients with metastatic disease and known metastatic sites from publicly available targeted sequencing data.
Results
Prostate cancer metastasis to the liver versus other sites of metastasis conferred a high hazard for death in patients with metastatic prostate cancer (HR: 3.96, 95% CI: 2.4–6.5, p < 0.0001). Genomic analysis of metastatic tissues of prostate cancer-specific genes demonstrated that liver metastases were more enriched with MYC amplification (29.5% vs. 9.8%, FDR = 0.001), PTEN deletion (42% vs. 20.8%, FDR = 0.005), and PIK3CB amplification (8.2% vs. 0.9, FDR = 0.005) compared to other sites. No point mutations were significantly associated with liver metastasis compared to other metastatic sites.
Conclusion
Liver metastases in prostate cancer are associated with poor survival and aggressive genomic features, including MYC-amplification, PTEN-deletion, and PIK3CB-amplification. These findings could have prognostic, treatment, and trial implications.
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Funding
Dr. Mahal is funded by the Prostate Cancer Foundation, American Society for Radiation Oncology, Department of Defense, and the Sylvester Comprehensive Cancer Center.
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MA, CS, IF, and BM conducted the analysis, drafted the paper, and contributed to revisions. MA and AP contributed to data acquisition and critical revision for important content. RV, RC, SP, SK, RD, AK, DS, JS, and ADP contributed to the conception of the study, data acquisition, and critical revision for important content. MA, CS, and BM have responsibility for the final approval of the version to be published.
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Dr. Mahal is funded by the Prostate Cancer Foundation-American Society for Radiation Oncology Award to End Prostate Cancer (grant support). Dr. Franco is funded by an NIH NCI Center to Reduce Cancer Health Disparities Diversity Supplement, and ACRO Luther Brady Educational Award (grant support). Dr. Spratt has received personal fees: Janssen, Blue Earth, Boston Scientific, AstraZeneca, and funding from Janssen. The remaining authors declare that they have no conflicts of interest.
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Alshalalfa, M., Seldon, C., Franco, I. et al. Clinicogenomic characterization of prostate cancer liver metastases. Prostate Cancer Prostatic Dis 25, 366–369 (2022). https://doi.org/10.1038/s41391-021-00486-2
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DOI: https://doi.org/10.1038/s41391-021-00486-2
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