Automated, machine learning-based systems are described for the analysis and annotation (i.e., detection or delineation) of prostate cancer (PCa) on histologically-stained pathology slides of prostatectomy specimens. A technical framework is described for automating the annotation of predicted PCa that is based on, for example, automated spatial alignment and colorimetric analysis of both H&E and IHC whole-slide images (WSIs). The WSIs may, as one example, be stained with a particular triple-antibody cocktail against high-molecular weight cytokeratin (HMWCK), p63, and α-methylacyl CoA racemase (AMACR).