Measurement of Natural Killer Cell Activity in Whole Blood in Men Being Screened for Prostate Cancer With Biopsy

The NK Vue diagnostic test for natural killer cell activity uses the principle of stimulation of whole blood with a proprietary cytokine followed by the quantitative detection of interferon-gamma using an immunoassay. NK Vue is intended to be used for the monitoring of the immune status of individuals. Measurement of NK cell activity could be a useful tool for assessing changes in immunosurveillance in patients with conditions or diseases where NK cell activity has been shown to be affected.

• IVDD for NK cell activity in whole blood (Diagnostic test), also known as NK Vue: Two samples of one mL of blood (for baseline IFN-gamma activity and for NK cell activity) and blood samples collected for C-Reactive Protein and White Blood Cell Count, taken up to 8 weeks prior to biopsy and before treatment with antibiotics.

Primary outcomes

• The ability of NK cell activity to predict prostate cancer (yes/no) on biopsy [NK cell activity is measured up to 8 weeks prior to biopsy and prior to starting any antibiotic treatment]: Test performance of NK Vue will be assessed by logistic regression, both unadjusted and adjusted for the effects of at least PSA, age, digital rectal examination, and family history

Secondary outcomes

• The ability of NK cell activity to predict tumor grade (Gleason 2-6 vs. no cancer; Gleason 7-10 vs. no cancer) [NK cell activity is measured up to 8 weeks prior to biopsy and prior to starting any antibiotic treatment]: Test performance of NK Vue will be assessed by multinomial logistic regression, using the following known predictors of prostate cancer: age, ethnicity, PSA history, family history of prostate cancer, prostate volume, digital rectal examination findings, and number of prior biopsies.
• Test performance metrics of NK Vue and PSA (each alone) [NK cell activity is measured up to 8 weeks prior to biopsy and prior to starting any antibiotic treatment]: The sensitivity, specificity, positive and negative predictive values for the detection of prostate cancer, will be calculated using Receiver Operating Characteristics analysis (at a cut-off of 4 ng/mL for PSA and at a cut-off of 200 pg/mL for NK Vue). Other cut-offs may be used to perform additional statistical analyses for test performance.
• Impact of combination of NK Vue and PSA on the test performance of PSA [NK cell activity is measured up to 8 weeks prior to biopsy and prior to starting any antibiotic treatment]: The sensitivity, specificity, positive and negative predictive values for the detection of prostate cancer, will be calculated using Receiver Operating Characteristics analysis under combined conditions.

Sex: Male, ages: 18 Years to any

Inclusion Criteria:

1. Male aged ≥ 18 years old
2. Able to read and sign an approved informed consent form
3. Soon to be undergoing a needle prostate biopsy for suspected prostate cancer; patients with a history of prior biopsy are not excluded provided the biopsy was negative
4. All prior and current recorded PSA levels are < 11 ng/mL (minimum of 2 values must be available)
5. Digital Rectal Exam performed or scheduled to be performed prior to biopsy

Exclusion Criteria:

1. Any other established malignancy with the exception of basal cell carcinoma
2. At time of blood collection, an active infection (eg bacterial, viral etc.) as declared by the patient
3. Chronic inflammatory condition requiring anti-inflammatory treatment such as rheumatoid arthritis, Crohn's or ulcerative colitis, Lupus or any connective tissue condition which, in the opinion of the investigator, might affect the immune response
4. Presently taking any of the following classes of medications on a regular basis:

   * 5-alpha reductase inhibitors
   * Anti-inflammatories, with the exception of low dose (81 mg) acetylsalicylic acid
   * Anti-androgens
   * Testosterone replacement therapy

• Barkin J, Rodriguez-Suarez R, Betito K. Association between natural killer cell activity and prostate cancer: a pilot study. Can J Urol. 2017 Apr;24(2):8708-8713. PMID 28436356
• Koo KC, Shim DH, Yang CM, Lee SB, Kim SM, Shin TY, Kim KH, Yoon HG, Rha KH, Lee JM, Hong SJ. Reduction of the CD16(-)CD56bright NK cell subset precedes NK cell dysfunction in prostate cancer. PLoS One. 2013 Nov 4;8(11):e78049. doi: 10.1371/journal.pone.0078049. eCollection 2013. PMID 24223759

• Neil E Fleshner, MPH,MD,FRCSC, Principal investigator, University Health Network, Toronto