Less invasive decision support tools are desperately needed to identify occult high-risk disease in men with prostate cancer (PCa) on an active surveillance (AS). For a variety of reasons, many men on AS with low or intermediate risk disease forgo the necessary repeat surveillance biopsies needed to identify potentially higher risk PCa. Here, we describe the development of a blood-based immunocyte transcriptomic signature to identify men harboring occult aggressive PCa. We then validate it on a biopsy-positive population with the goal of identifying men who should not be on AS and confirm those men with indolent disease who can safely remain on AS. This model uses subtraction-normalized immunocyte transcriptomic profiles to risk stratify men with PCa that could be candidates for AS.
Men were eligible for enrollment in the study if they were determined by their physician to have a risk profile that warranted prostate biopsy. Both training (n = 1017) and validation cohort (n = 1198) populations had blood samples drawn coincident to their prostate biopsy. Purified CD2+ and CD14+ immune cells were obtained from peripheral blood mononuclear cells and RNA was extracted and sequenced. To avoid overfitting and unnecessary complexity, a regularized regression model was built on the training cohort to predict PCa aggressiveness based on the National Comprehensive Cancer Network (NCCN) prostate cancer guidelines. This model was then validated on an independent cohort of biopsy-positive men only, using NCCN unfavorable intermediate risk and worse as an aggressiveness outcome, identifying patients that were not appropriate for AS.
The best final model for the AS setting was obtained by combining an immunocyte transcriptomic profile based on two cell types with prostate-specific antigen (PSA) density and age, reaching an AUC of 0.73 (95% confidence interval (CI): 0.69 to 0.77). The model significantly outperforms (P < .001) PSA density as a biomarker, which has an AUC of 0.69 (95% CI: 0.65-0.73). This model yields an individualized patient risk score with 90% NPV and 50% PPV.
While further validation in an intended-use cohort is needed, the immunocyte transcriptomic model offers a promising tool for risk stratification of individual patients who are being considered for AS.
The Journal of urology. 2023 Dec 26 [Epub ahead of print]
Leander Van Neste, Ricardo Henao, Kirk J Wojno, Jorge Signes, Jessica DeHart, Angela Busta, Elyse Marriott, Marian Willing, Andrea Argentini, Patrick M Hurley, Howard Korman, Jason Hafron, Mathew Putzi, Chris M Pieczonka, Lawrence I Karsh, David S Morris, Amin I Kassis, Philip W Kantoff
Immunis.AI, Royal Oak, Michigan., Duke University, Durham, North Carolina., David H Murdock Research InstituteI, Kannapolis, North Carolina., BioLizard, Ghent, Belgium., Comprehensive Urology, Royal Oak, Michigan., Michigan Institute of Urology, Troy, Michigan., Austin Urology, Austin, Texas., Associated Medical Professionals, Syracuse, New York., The Urology Center of Colorado, Denver, Colorado., Urology Nashville, Nashville, Tennessee., Convergent Therapeutics, Boston, Massachusetts.