On October 25, 2022 Veracyte, Inc. (Nasdaq: VCYT) reported that new data demonstrating that a genomic signature derived from the company’s Decipher GRID database could help determine which men experiencing prostate cancer progression following radical prostatectomy (RP) would benefit from dose-intensified salvage radiotherapy (SRT) (Press release, Veracyte, OCT 25, 2022, View Source [SID1234622350]). The data, from a randomized, phase 3 trial, were presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting 2022 (abstract #160) taking place October 23-26, 2022, in San Antonio, Texas.
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Post-Operative Radiation Therapy Outcomes Score (PORTOS) is a gene-expression signature of 24 DNA damage, repair and immune pathway genes previously shown to predict benefit from postoperative radiotherapy. In the current study, researchers evaluated the biomarker’s predictive ability for SRT dose among 226 men in the prospective open-label, multicenter, randomized phase 3 Swiss Group for Clinical Cancer Research (SAKK) 09/10 trial. This trial, which randomized men with biochemically recurrent disease after RP to conventional or dose-intensified salvage radiotherapy without the addition of androgen deprivation therapy (ADT), did not report a clinical benefit for dose-intensification.
The new data shared at ASTRO show that the subset of men with higher PORTOS scores had substantial improvement in clinical-progression-free survival (CPFS) with the higher dose of SRT (70Gy). Specifically, those men with higher PORTOS scores had an absolute benefit of 45% CPFS at 5 years with dose-intensified SRT compared with the standard dose, while the men with lower PORTOS scores had an absolute benefit of -10% (p-interaction=0.003).
"Our findings suggest that the Decipher PORTOS signature may be a valuable tool to help physicians better identify those prostate cancer patients who should receive dose-intensified salvage radiotherapy when their disease recurs following radical prostatectomy," said Alan Dal Pra, M.D., member of Sylvester Comprehensive Cancer Center, director of Clinical Research and associate professor of radiation oncology at the University of Miami Miller School of Medicine, and lead author on the ASTRO abstract. "Dependent on further studies, this could be the first predictive biomarker to help physicians personalize radiotherapy dose in the postoperative prostate cancer setting."
It is estimated that up to 40 percent of men with intermediate- or high-risk prostate cancer may experience a biochemical disease recurrence after RP, which is characterized by rising levels of serum prostate-specific antigen (PSA).1 For those men who experience a rising PSA, treatment with 64-72 Gy SRT is now standard of care, though treatment with higher doses can lead to greater urinary and bowel side effects.
"This study demonstrates how gene-expression signatures can help identify the men who are most likely to benefit from more radiation, and help inform physician and patient decisions regarding their radiation treatment after surgery," said Elai Davicioni, Ph.D., Veracyte’s medical director for Urology. "We very much value our multi-year research efforts with the Swiss SAKK study group, and look forward to our continued collaborations with leading academic and industry partners to further validate GRID-derived predictive biomarkers that may help physicians better individualize the care of men with prostate cancer."
About Decipher GRID
The Decipher Genomics Resource for Intelligent Discovery (GRID) database includes more than 100,000 whole-transcriptome profiles from patients with urologic cancers and is used by Veracyte and its research partners to help advance understanding of prostate and other urologic cancers. PORTOS is among more than 400 biomarkers that have been discovered or developed using Decipher GRID and are available on a Research Use Only basis to physicians who have ordered the Decipher Prostate Genomic Classifier.