Genomic Sequencing May Help To Determine Prognosis in High-risk Prostate Cancer
Researchers obtained biopsies from 49 men with high-risk prostate cancer to determine genomic and T cell intratumoral heterogeneity.
Genomic testing and immunomodulation may help to improve outcomes among patients with prostate cancer, according to a study published in the Annals of Oncology.1
While low-risk prostate cancer carries a good prognosis, high-risk disease carries a 10-year cancer-specific survival rate of 20% to 25%. Correctly determining which patients have high-risk disease is important for sparing low-risk patients radical treatment.
To determine whether genomic testing can mark high-risk disease and reveal potential immunomodulatory targets, researchers obtained biopsies from 49 men with high-risk prostate cancer and conducted sequencing for genomic and T cell intratumoral heterogeneity.
The study (PROGENY; ClinicalTrials.gov Identifier: NCT02022371) included 23 men from the original 49 plus 2 additional patients who met the predefined criteria for genetic and T cell analysis. The researchers sequenced 79 tumor regions from the 25 included patients.
The researchers identified “4484 exonic somatic nucleotide variations (SNV) (3382 non-silent), of which 1962 were ubiquitous, 495 were shared, and 2027 were private.”
Extensive somatic copy number alteration (SCNA) heterogeneity was also found. Patients with metastatic hormone-naive disease had higher SCNA burden.
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Loss of mismatch repair (MMR) proteins was linked with intratumoral and intertumoral T cell heterogeneity; Wnt signaling was linked with immune suppression.
The authors concluded that genomic aberrations are “associated with altered patterns of immune infiltrate,” and further that Wnt may be a biomarker for immunomodulatory therapy.
- Linch M, Goh G, Hiley C, et al. Intratumoural evolutionary landscape of high risk prostate cancer: the PROGENY study of genomic and immune parameters. Ann Oncol. In press.