JU INSIGHT Optimizing a Subtraction-Normalized Immunocyte Profile for Prostate Cancer Active Surveillance Stratification

By: Leander Van Neste, PhD, Immunis.AI, Royal Oak, Michigan; Ricardo Henao, PhD, Duke University, Durham, North Carolina; Kirk J. Wojno, MD, Immunis.AI, Royal Oak, Michigan; Jorge Signes, PhD, David H. Murdock Research Institute, Kannapolis, North Carolina; Jessica DeHart, MS, Immunis.AI, Royal Oak, Michigan; Angela Busta, MS, Immunis.AI, Royal Oak, Michigan; Elyse Marriott, MS, Immunis.AI, Royal Oak, Michigan; Marian Willing, MS, Immunis.AI, Royal Oak, Michigan; Andrea Argentini, PhD, BioLizard, Ghent, Belgium; Patrick M. Hurley, MD, Comprehensive Urology, Royal Oak, Michigan; Howard Korman, MD, Comprehensive Urology, Royal Oak, Michigan, Wayne State University School of Medicine, Detroit, Michigan; Jason Hafron, MD, Michigan Institute of Urology, Troy; Mathew Putzi, MD, Austin Urology, Texas; Chris M. Pieczonka, MD, Associated Medical Professionals, Syracuse, New York; Lawrence I. Karsh, MD, The Urology Center of Colorado, Denver; David S. Morris, MD, Urology Nashville, Tennessee; Amin I. Kassis, PhD, Immunis.AI, Royal Oak, Michigan; Philip W. Kantoff, MD, Convergent Therapeutics, Boston, Massachusetts | Posted on: 19 Apr 2024

Van Neste L, Henao R, Wojno KJ, et al. Optimizing a subtraction-normalized immunocyte profile for prostate cancer active surveillance stratification. J Urol. 2024;211(3):415-425.

Study Need and Importance

Active surveillance (AS) is considered more frequently for men diagnosed with low-grade, low-risk prostate cancer to avoid the overtreatment of indolent disease in the past. However, other studies have shown that 20% to 40% of all men placed on AS harbor aggressive disease, which is only detected after (multiple) serial repeat biopsies due to the limitations of prostate biopsy.

What We Found

In this study, we developed and optimized a risk score for prostate cancer AS. Using the patient as his own control, by applying a subtraction normalization, we are stratifying the risk of harboring aggressive prostate cancer and suitability for AS by profiling 2 classes of immunocytes. The risk score presented in this study harnesses the power of the immune system to identify those men at increased risk of harboring aggressive prostate cancer vs those who truly belong on AS. The Figure shows a decision curve analysis illustrating the net benefit of this risk score and compares it with a clinical base model including age and PSA density as risk factors. While this clinical model shows limited benefit over the relevant range, the addition of the immunocyte transcriptomic profile results in a strong net benefit for men on AS.

Figure. Decision curve analysis on the validation set (biopsy-positive only) depicting the net benefit of the model combining the immunocyte transcriptomic profile with PSA density and age over the model including these clinical risk factors only. For reference, the situation where all men undergo radical treatment for clinically significant prostate cancer (gray line) and the situation where no men undergo further treatment (black line) are also depicted.

Limitations

These results were produced in the biopsy-positive subset of men undergoing prostate biopsy and need to be validated in an intended-use population. Patient risk was classified based on the National Comprehensive Cancer Network prostate cancer guidelines as a surrogate for long-term outcomes like disease-specific mortality and metastasis, which are considered good surrogates.

Interpretation for Patient Care

Disease reclassification based on repeat biopsy results is an important, practical, and clinically actionable end point. If these results can be confirmed in a true AS setting, this offers a minimally invasive alternative to evaluate and monitor patients for AS.