New Screening Test Improves Detection of Prostate Cancer Using Circulating Tumor Cells and Prostate-Specific Markers

Abstract

The current screening-test for prostate cancer, affecting 10% of men worldwide, has a high false negative rate and a low true positive rate. A more reliable screening test is needed. Circulating-Tumor-Cells (CTC) provide a biomarker for early carcinogenesis, cancer progression and treatment effectiveness. The cytology-based ISET®-CTC Test is a clinically validated blood test with high sensitivity and specificity. This study aimed to evaluate the ISET®-CTC test combined with prostate-specific-marker staining as a screening test for the detection of prostate cancer. We selected a group of 47 men from our ongoing CTC screening study involving 2,000 patient-tests from Sep-2014 to July-2019, who also underwent standard diagnostic cancer testing before or after CTC testing. While 20 of the 47 men were diagnosed with prostate cancer before the ISET®-CTC test, 27 men underwent screening. We studied the CTC identified in 45 CTC-positive men by Immuno-Cyto-Chemistry (ICC) assays with the prostate-specific-marker PSA. CTC were ICC-PSA-marker positive in all men diagnosed with primary prostate cancer (n = 20). Secondary cancers were detected in 63% (n = 7/11) of men with mixed CTC-population (ICC-PSA-positive/ICC-PSA-negative). Of the 27 men screened, 25 had CTC, and 84% of those (n = 20) were positive for the prostate-specific-PSA-marker. Follow-up testing suggested suspected prostate cancer in 20/20 men by a positive PSMA-PET scan, and biopsies performed in 45% (n = 9/20) men confirmed the diagnosis of early prostate cancer. Kidney cancer or B-cell lymphoma were detected in two men with ICC-PSA-marker negative CTC. Our study suggests that the combination of ISET®-CTC and ICC-PSA-marker-testing has an estimated positive-predictive-value (PPV) of 99% and a negative-predictive-value (NPV) of 97%, providing a more reliable screening test for prostate cancer than the standard PSA-blood-test (PPV = 25%; NPV = 15.5%). Our findings warrant further studies to evaluate the new test's potential for prostate cancer screening on a population level.

Keywords: cancer screening; circulating tumor cells (CTC); early detection; prostate cancer; prostate specific antigen (PSA).

Figure 1

Study flow chart. CTC, circulating tumor cell; ED, early detection; ICC, immuno-cyto-chemistry; incl, including; PC, prostate cancer; PSA, prostate specific Antigen; (+)/(–), positive/negative test result.

Figure 2

Immuno-cyto-chemistry (ICC) on ISET®-CTC with PSA-antibody. (A–D) screened males with PSA (+) stained CTC, (E) male with PROSTATE CANCER (positive control), and (F) a female breast cancer patient (negative control). The black outline of the Circulating Tumor Cell (CTC) (red arrows) depicts a positive ICC marker stain, no black outline around the CTC depicts a negative ICC marker stain (green arrow).