New Prostate Cancer Screening Method Could Reduce Risk of Overdiagnosis

The method had high rates of sensitivity and specificity, although its sensitivity was somewhat lower in cases of localized prostate cancer.

Investigators say they have developed a new noninvasive method of screening for prostate cancer that may help reduce the risk of false negatives and overdiagnosis. The report was published in Cancer Medicine.

The study authors explained that prostate cancer is one of the most common cancer types in the world and has very high survival rates when detected early. Yet, the primary method of screening patients for prostate cancer, serum prostate-specific antigen (PSA), has such low sensitivity that it can lead to a significant rate of false positives in asymptomatic men and carries a high risk of false negatives in men with advanced undifferentiated cancers.

“More sensitive and specific methods which can provide for more effective prostate cancer detection are required to reduce morbidity and mortality from this disease,” they wrote.

The investigators decided to see whether prostate adenocarcinoma circulating tumor cells (PrAD-CTCs) might be a better indicator of prostate cancer. CTCs are tumor-derived cells that are circulating in the blood, they noted, and previous studies have suggested the cells are ubiquitous in prostate cancer.

However, the authors also noted that it can be difficult to efficiently enrich and harvest sufficient CTCs. They said most previous studies of CTCs have used epitope capture using epithelial cell adhesion molecule (EpCAM) followed by immunostaining for cytokeratins (CK).

“A critical limitation of this approach is its acknowledged inability to effectively enrich and detect CTCs where the expression of target biomarkers such as EpCAM and CK can be significantly lower than tumor tissue or reference cell lines,” they wrote.

In the new study, the investigators used a method based on functional enrichment of PrAD-CTCs from blood samples “followed by their identification by immunostaining for pan-cytokeratins, prostate specific membrane antigen, alpha methyl-acyl coenzyme-A racemase, EpCAM, and common leukocyte antigen.”

The investigators first used analytical validation studies to establish clinical performance characteristics and then evaluated those characteristics in a case-control study using 160 cases of known prostate cancer and 800 healthy controls. They then evaluated the method in a prospective study of 210 people with suspected cases of prostate cancer.

In the case-control study, the test showed 100% specificity and 100% sensitivity in differentiating prostate cancer cases from healthy controls. In the prospective study, the sensitivity was 91.2% and the specificity was 100% in differentiating cancer from benign conditions, the study authors reported.

They noted some limitations to their study. It would not detect nonadenocarcinoma cancer types, and it was less sensitive for localized prostate cancer in the prospective study (about 75% sensitivity). The study was also conducted in a case set with lower-than-average rates of early stage disease, they noted.

However, they said the results of the study, plus the high unmet need for better screening, suggest their method has potential to reduce the need for invasive biopsies and the risk of overdiagnosis.

“The potential benefits of the test are compelling and support the need for further prospective large cohort clinical studies to determine the performance characteristics of the test for detection of prostate cancer, especially localized disease,” they wrote.


Limaye S, Chowdhury S, Rohatgi N, et al. Accurate prostate cancer detection based on enrichment and characterization of prostate cancer specific circulating tumor cells. Cancer Med. Published online January 30, 2023. doi:10.1002/cam4.5649

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