Gene Assay May Help Identify Patients at Risk for Metastasis After Surgery/EBRT
Clinical Study Title:
A Metastatic Biology Gene Expression Assay to Predict the Risk of Distant Metastases in Patients With Localized Prostate Cancer Treated With Primary Radical Treatment
Clinical Study Abstract:
Approximately 20% of patients with organ-confined prostate cancer develop disease recurrence following surgery or external beam radiotherapy (EBRT). Investigators hypothesized that a molecularly defined subgroup of patients may have metastatic potential at presentation, which in turn may be an impetus for recurrence. They developed a 70-gene expression assay and tested it on formalin-fixed, paraffin-embedded tumor specimens from 322 surgical patients and 248 patients treated with EBRT. Regions of highest Gleason grade were identified for macrodissection, RNA extraction, and gene expression analysis. The specimens were evaluated with the metastatic biology assay, and designated positive or negative using a prespecified cut-off. On multivariate analysis, the assay was significantly associated with biochemical failure for surgical patients (hazard ratio [HR] 1.67 [1.16-2.38]; P=0.0059) and for EBRT patients (HR 2.26 [1.26-4.04]; P=0.0062), and significantly associated with distant metastases for surgical patients (HR 3.39 [1.88-6.12]; P=0.0001) and for EBRT patients (HR 3.26 [1.27-8.30]; P=0.0137).
The authors concluded that this metastatic biology assay predicts biochemical failure and distant metastases in patients with prostate cancer treated with surgery or EBRT. Also, they suggested that the assay may help identify patients at risk of metastatic disease for additional treatment aimed at preventing disease recurrence.
Jain S, Lyons C, Walker SM, et al. A metastatic biology gene expression assay to predict the risk of distant metastases in patients with localized prostate cancer treated with primary radical treatment. J Clin Oncol. 2017;35(suppl 6S):Abstract 11.
Co-Director, Urologic Oncology
This study adds to the emerging data regarding the clinical use of molecular biomarkers in the management of prostate cancer. The basis of appropriate treatment selection is the accurate risk stratification of prostate cancer patients at the time of their diagnosis. Although the tumor/node/metastasis (TNM) staging, prostate-specific antigen (PSA), and Gleason group predict the clinical course for many patients, clinicians and patients are often frustrated by seemingly low- to-intermediate-risk cancers behaving in a more aggressive fashion.
Genomic alterations may be the reason that an otherwise low-risk patient may develop a biochemical recurrence after his primary therapy and why certain patients are more prone to develop metastatic disease and have a poor clinical outcome. Identification of biomarkers to help select those patients who are at higher risk for local and distant progression has the potential to change how we counsel patients regarding their treatment options.
“Although the TNM staging, PSA, and Gleason group predict the clinical course for many patients, clinicians and patients are often frustrated by seemingly low- to-intermediate-risk cancers behaving in a more aggressive fashion.”
An unmet challenge is the external validation of these prognostic biomarker studies to clarify whether they can assist clinicians in the decision-making process. A prospective analysis incorporating these new assays into our current algorithms is needed.