Low-cost marker panel, CCP score compared

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A new study examining gene expression assays for stratifying prostate cancer risk is suggesting that it may be possible to develop lower-cost alternatives and expand access.

Researchers compared a low-cost immunohistochemistry (IHC) marker panel with a cell-cycle progression (CCP) assay for the prediction of outcome after radical prostatectomy. A simple IHC approach might match the performance of far more expensive amplification-based tests, they reported at the Genitourinary Cancers Symposium in San Francisco.

The authors compared the prognostic utility of a low-cost IHC panel consisting of three validated markers with an RNA-expression-based CCP score. The analysis included 5,748 patients with prostate cancer, and the authors were able to identify 424 men with localized disease treated with radical prostatectomy.

“We compared the results of a commercially available gene expression test assessing a panel of cell-cycle progression genes with a limited panel of immunohistochemical markers including PTEN, Ki67, and ERG. We found that both the status of PTEN expression and the cell-cycle progression panel were independently associated with the risk of death from prostate cancer,” said first author Michael Leapman, MD, assistant professor of urology at Yale University School of Medicine, New Haven, CT.

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After adjusting for clinical and pathologic factors, a model including PTEN offered slightly better discrimination of the risk of death or metastasis from prostate cancer.

“We were fascinated to observe that a simple immunohistochemistry approach that can be performed by many pathology laboratories might match the performance of far more expensive amplification-based tests,” Dr. Leapman told Urology Times.

The authors compared models using concordance index testing. The median age at treatment was 59 years, and the men were followed for a median of 114 months post prostatectomy. In this cohort, 27% of men experienced biochemical recurrence and 4% developed metastasis or prostate-specific mortality at 10 years after prostatectomy.

The authors adjusted for the Cancer of the Prostate Risk Assessment Score (CAPRA-S) and found that a combination of three factors (PTEN loss, high Ki67, and positive ERG expression) was independently associated with risk of biochemical recurrence (HR: 2.3, 95% CI: 1.1-4.7) and metastasis/prostate cancer-specific mortality (HR: 8.3, 95% CI: 3.3-21.2). In a separate model, the authors included CAPRA-S, an IHC panel, and an RNA-expression-based cell-cycle progression (CCP) score. They found that the CCP score was independently associated with both recurrence and metastasis (HR: 1.9, 95% CI: 1.5-2.5) and prostate cancer-specific mortality (HR: 2.5, 95% CI: 1.5-4.1). IHC expression status of PTEN/Ki67/ERG was found to be an independent predictor of both metastasis and prostate cancer-specific mortality.

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The addition of the CCP assay marginally improved the c-index of a combined IHC panel and CAPRA-S model from 0.78 to 0.81 for the prediction of metastasis and prostate cancer-specific mortality.

“Our findings call attention to the need to consider cost and simplicity when developing biomarkers for risk prediction in prostate cancer. There is a clear need to improve estimates of disease outcome for men with prostate cancer; however, the economic implications of costly tests are rarely considered,” Dr. Leapman said.

The results of this study, which was made possible by Zero Cancer Foundation, Jim Lafferty Memorial Research Grant, do not indicate that IHC should supplant genomic profiling, Dr. Leapman noted. Instead, the analysis suggests that an appreciation for lower-cost alternatives may be an important step to expand access and maintain sustainability.

One of Dr. Leapman’s co-authors is a consultant/adviser for several pharmaceutical companies.