A novel, urine-based, three-biomarker panel demonstrated significant accuracy and promising sensitivity and specificity for the detection of prostate cancers during development and validation testing, according to findings published in eBioMedicine.
“This new biomarker panel offers a promising, sensitive, specific, noninvasive diagnostic test for prostate cancer,” stated senior study author Ranjan Perera, PhD, Director of the Center for RNA Biology, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, and Professor of Oncology and Neurosurgery at the Johns Hopkins University School of Medicine. “It has the potential to accurately detect prostate cancer, reduce unnecessary biopsies, improve diagnostic accuracy in prostate-specific antigen (PSA)-negative patients, and serve as the foundation for both laboratory-developed and in vitro diagnostic assays.”
Rationale and Study Methods
Prostate cancer screening is widely done with PSA testing even though its accuracy is limited. The researchers sought out a panel of urinary RNA biomarkers that would have greater diagnostic accuracy than PSA testing for prostate cancer detection.
“There is a real need for non–PSA-based biomarkers for prostate cancer, and urine is quite easy to collect in the clinic,” said study co-author Christian Pavlovich, MD, the Bernard L. Schwartz Distinguished Professor of Urologic Oncology at Johns Hopkins and Program Director for the Prostate Cancer Active Surveillance Program. “Most urologists feel that an accurate urinary biomarker would be a valuable addition to our current diagnostic armamentarium.”
Investigators completed RNA sequencing analysis of exfoliated cells in urine specimens. They identified 50 candidate RNAs and narrowed the possible biomarkers down with quantitative polymerase chain reaction testing in pooled urine until they found three biomarkers with the greater specificity and sensitivity for the panel: TTC3, H4C5, and EPCAM.
The researchers analyzed the performance of the panel in a case-control study that was split into a development and validation dataset, totaling urine samples from almost 900 individuals, including patients with prostate cancer both before and after prostatectomy and healthy individuals. The expression of the biomarkers was also confirmed in tissue specimens and in vitro.
Key Study Findings
In the development dataset, the three-biomarker panel was able to identify prostate cancer accurately with an area under the curve of 0.96 (95% confidence interval [CI] = 0.94–0.98) compared with an area under the curve of 0.83 (95% CI = 0.77–0.88) for urinary PCA3 RNA. In the validation dataset, the area under the curve for the novel panel was 0.92 (95% CI = 0.89–0.94) vs 0.76 (95% CI = 0.72–0.80) for PCA3.
Postprostatectomy, the urine biomarkers were almost completely eliminated and were found to originate in prostate tissue at both the RNA and protein levels.
The panel was also to diagnose prostate cancer in PSA-negative cases 86% of the time in the validation set, and was able to distinguish prostate cancer from benign prostate conditions, such as prostatitis and benign prostatic hyperplasia, 84% to 89% of the time.
A functional study also showed that depletion of TTC3 could suppress tumor growth in vitro and in vivo.
“This test has the potential to help physicians improve diagnostic accuracy of prostate cancer, reducing unnecessary interventions while allowing early treatment for those who need it,” said study co-author Vipul Patel, MD, Director of Urologic Oncology at AdventHealth Cancer Institute in Celebration, Florida; Medical Director of Global Robotics for AdventHealth’s Global Robotics Institute; and Founder of the International Prostate Cancer Foundation. “On behalf of physicians and patient globally, I advocate for further study and progress for these biomarkers.”
Disclosure: The study was supported by the International Prostate Cancer Foundation, Johns Hopkins Kimmel Cancer Center, the Bankhead-Coley Cancer Research Program, and the Maryland Innovation Initiative Grant. For full disclosures of the study authors, visit thelancet.com.
