Clinical Proof-of-concept of a Novel Platform Utilizing Biopsy-derived Live Single Cells, Phenotypic Biomarkers, and Machine Learning Toward a Precision Risk Stratification Test for Prostate Cancer Grade Groups 1 and 2 (Gleason 3 + 3 and 3 + 4).

Objective: To examine the ability of a novel live primary-cell phenotypic (LPCP) test to predict postsurgical adverse pathology (P-SAP) features and risk stratify patients based on SAP features in a blinded study utilizing radical prostatectomy (RP) surgical specimens.

Methods: Two hundred fifty-one men undergoing RP were enrolled in a prospective, multicenter (10), and proof-of-concept study in the United States. Fresh prostate samples were taken from known areas of cancer in the operating room immediately after RP. Samples were shipped and tested at a central laboratory. Utilizing the LPCP test, a suite of phenotypic biomarkers was analyzed and quantified using objective machine vision software. Biomarkers were objectively ranked via machine learning-derived statistical algorithms (MLDSA) to predict postsurgical adverse pathological features. Sensitivity and specificity were determined by comparing blinded predictions and unblinded RP surgical pathology reports, training MLDSAs on 70% of biopsy cells and testing MLDSAs on the remaining 30% of biopsy cells across the tested patient population.

Results: The LPCP test predicted adverse pathologies post-RP with area under the curve (AUC) via receiver operating characteristics analysis of greater than 0.80 and distinguished between Prostate Cancer Grade Groups 1, 2, and 3/Gleason Scores 3 + 3, 3 + 4, and 4 + 3. Further, LPCP derived-biomarker scores predicted Gleason pattern, stage, and adverse pathology with high precision-AUCs>0.80.

Conclusion: Using MLDSA-derived phenotypic biomarker scores, the LPCP test successfully risk stratified Prostate Cancer Grade Groups 1, 2, and 3 (Gleason 3 + 3 and 7) into distinct subgroups predicted to have surgical adverse pathologies or not with high performance (>0.85 AUC).