From the Editor

From the Desk of the Associate Editor: The Relationship of the B7H3 Immune Checkpoint to Prostate Cancer Outcomes

Andrew Armstrong
September 11, 2018

Prostate cancer is known to be an immune evasive tumor, often coexisting with areas of inflammation in the primary site, but without over-expression of the traditional PD-1/PD-L1 immune checkpoint, unlike many other cancer subtypes.  While certain prostate cancer subsets like microsatellite high (MSI high) and CDK12 deleted disease may respond well to single agent PD-1 pathway inhibitors, in most (>90%) of prostateadenocarcinomas, other immunosuppressive molecules and pathways are likely to be of greater importance and have yet to be adequately targeted.  Here is where B7-H3 may be relevant.

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stephen j freedland

Stephen J. Freedland, MD

Stephen J. Freedland, MD, is director of the Center for Integrated Research in Cancer and Lifestyle and co-director of the Cancer Genetics and Prevention Program and Associate Director for Faculty Development at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute. He is also a faculty physician in the Division of Urology within the Department of Surgery at Cedars-Sinai. He has served on numerous American Urological Association guideline panels for prostate cancer and co-chaired a prostate cancer guideline panel for the American Society of Clinical Oncology.

Dr. Freedland's clinical area of expertise focuses on urological diseases, particularly benign prostatic hyperplasia and prostate cancer. His approach toward cancer prevention and awareness focuses on treating the whole patient, not just the disease, by combining traditional Western medicine with complementary holistic interventions. His research interests include investigations on urological diseases and the role of diet, lifestyle and obesity in prostate cancer development and progression, as well as prostate cancer among racial groups and risk stratification for men with prostate cancer.


PCAN: September 2018

Correlation of B7-H3 with Androgen Receptor, Immune Pathways and Poor Outcome in Prostate Cancer: An Expression-based Analysis – Full Text Article

BACKGROUND: B7-H3 (CD276), part of the B7 superfamily of immune checkpoint molecules, has been shown to have an immunomodulatory role. Its regulation, receptor and mechanism of action remain unclear. B7-H3 protein expression correlates with prostate cancer outcomes, and humanized monoclonal antibodies (that is, enoblituzumab) are currently being investigated for therapeutic use. Here we used genomic expression data to examine the relationship between B7-H3 mRNA expression and prostate cancer.
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PCAN: August 2018

Longitudinal Assessment of Urinary PCA3 for Predicting Prostate Cancer Grade Reclassification in Favorable-Risk Men During Active Surveillance - Full Text Article

BACKGROUND: To assess the utility of urinary prostate cancer antigen 3 (PCA3) as both a one-time and longitudinal measure in men on active surveillance (AS).

METHODS: The Johns Hopkins AS program monitors men with favorable-risk prostate cancer with serial PSA, digital rectal examination (DRE), prostate magnetic resonance imaging and prostate biopsy. Since 2007, post-DRE urinary specimens have also been routinely obtained. Men with multiple PCA3 measures obtained over ⩾3 years of monitoring were included. The utility of first PCA3
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PCAN: July 2018

Comparison of Multiparametric Magnetic Resonance Imaging and PSMA PET/CT to Prostatectomy Histopathology - Full Text Article

Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can be used to locate lesions based on PSMA avidity, however, guidelines on its use are limited by its infancy. We aimed to compare multiparametric magnetic resonance imaging (mpMRI) and PSMA PET/CT to prostatectomy histopathology.
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PCAN: June 2018

Periprostatic Adipose Inflammation is Associated with High-Grade Prostate Cancer - Full Text Article

Background: Obesity, a cause of subclinical inflammation, is associated with increased risk of high-grade prostate cancer (PC) and poor outcomes. Whether inflammation occurs in periprostatic white adipose tissue (WAT), and contributes to the negative impact of obesity on PC aggressiveness, is unknown.

Methods: In a single-center, cross-sectional design, men with newly diagnosed PC undergoing radical prostatectomy were eligible for study participation. The primary objective was to examine the prevalence of periprostatic WAT inflammation defined by the presence of crown-like structures (CLS-P) as detected by CD68 immunohistochemistry. Secondary objectives
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PCAN: May 2018

Post Prostatectomy Outcomes of Patients with High-risk Prostate Cancer Treated with Neoadjuvant Androgen Blockade - Full Text Article

Background: Patients with high-risk prostate cancer have an increased likelihood of experiencing a relapse following radical prostatectomy (RP). We previously conducted three neoadjuvant androgen-deprivation therapy (ADT) trials prior to RP in unfavorable intermediate and high-risk disease.

Methods: In this analysis, we report on the post-RP outcomes of a subset of patients enrolled in these studies. We conducted a pooled analysis of patients with available follow-up data treated on three neoadjuvant trials at three institutions. All patients received intense ADT prior to RP. The primary endpoint
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PCAN: April 2018

Utilization of Biopsy-Based Genomic Classifier to Predict Distant Metastasis after Definitive Radiation and Short-Course ADT - Full Text Article

BACKGROUND: We examined the ability of a biopsy-based 22-marker genomic classifier (GC) to predict for distant metastases after radiation and a median of 6 months of androgen deprivation therapy (ADT). 

METHODS: We studied 100 patients with intermediate-risk (55%) and high-risk (45%) prostate cancer who received definitive radiation plus a median of 6 months of ADT (range 3–39 months) from 2001–2013 at a single center and had available biopsy tissue. Six to ten 4 micron sections of the needle biopsy core with the highest Gleason score and percentage of tumor involvement were
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