Tumor size and genomic risk in localized prostate cancer

Purpose: Unlike many other cancers, measurement of primary prostate tumor size has no defined role in the management of localized prostate cancer. Here, we assess whether prostate tumor size is associated with aggressive tumor biology using biomarkers of genomic risk.

Materials and methods: We abstracted or imputed tumor size from the primary pathology reports of prostate cancers incorporated in The Cancer Genome Atlas. We used transcriptomic data to estimate the Cell Cycle Progression Score (CCPS, Prolaris), the Genomic Classifier Score (GCS, Decipher) and the Genomic Prostate Score (GPS, OncotypeDx), SChLaP1 expression, and copy number alteration percentage (%CNA) as well as hallmark gene set enrichment analysis.

Results: Tumor size and gene expression data was available for 267 men. On multivariable regression adjusted for Gleason Grade Group and tumor purity, tumor size was independently associated with the calculated (c)GCS, cGPS, SChLaP1 expression, and %CNA (P< 0.05), but not cCCPS. Gene set enrichment analysis demonstrated that tumors <5 cc, when adjusting for Gleason grade group, were enriched for androgen response genes, while tumors >5 cc were enriched for MYC targets and genes associated with epithelial mesenchymal transition.

Conclusions: Prostate tumor size is independently associated with established markers of genomic risk. This study nominates the size of a primary prostate cancer as candidate for inclusion in future novel risk scores seeking to quantify cancer aggressiveness.