Adding a CTC Test May Improve Prostate Cancer Diagnosis

Helen Leask

September 13, 2019

A novel blood test for prostate cancer has the potential to significantly improve patient stratification by prostate-specific antigen (PSA) and/or multiparametric MRI for biopsy and treatment, say the authors of a new study published online August 7 in the Journal of Urology.

The noninvasive diagnostic tool, which uses circulating tumor cell (CTC) analysis, can also identify clinically significant prostate cancer in pre-biopsy patients with high accuracy.

The benefits of such a tool might allow men to avoid biopsy and its risks of bleeding and infection, say lead author Yong-Jie Lu, MD, PhD, Queen Mary University of London, UK, and colleagues.

In the study, researchers enrolled 155 patients with treatment-naive prostate cancer and 98 pre-biopsy patients for CTC tally. RNA was extracted from the cells of 184 patients for gene expression analysis

In localized prostate cancer patients, 54% were scored as CTC positive, which was associated with higher Gleason score (P = .0003), risk group (P < .0001), and clinically significant prostate cancer (P < .0001). In the pre-biopsy group, positive CTC score in combination with PSA predicted clinically significant prostate cancer (AUC, 0.869).

The authors also state that a 12-gene panel prognostic for clinically significant prostate cancer was also identified. When that panel was combined with PSA level and CTC score, the AUC for clinically significant prostate cancer prediction was 0.927. Additionally, in cases with multiparametric MRI data, adding these tools to multiparametric MRI significantly increased the prediction accuracy (AUC, 0.936 vs 0.629).

The authors stress that, as this is a single-center study, the results need independent validation before the test becomes available to patients, which could take 3 to 5 years. Any subsequent approval by the US FDA could also take 3 to 5 years, according to the Queen Mary University of London press office.

There's a lot of room for improvement in the diagnosis of prostate cancer, say the authors.

They remind that prostate cancer is currently detected using PSA levels followed by a biopsy of the prostate. PSA can provide early diagnosis but is notoriously inaccurate. Half of men who test PSA positive do not have cancer on biopsy. Also, some prostate cancers are not fatal and can be left untreated, but it is difficult to reliably pinpoint these cancers. This means that many men with a high PSA go on to unnecessarily endure biopsy, surgery, and other treatments, with their attendant risks of bleeding and infection, and in the case of radical prostatectomy, urinary incontinence and erectile dysfunction.

"The issue with prostate cancer is that we want to detect the clinically significant cancer, but more than half of patients with elevated PSA don't have clinically significant cancer," said Lu.

PSA is not ideal because it has high sensitivity — meaning someone with prostate cancer will always have high PSA — but low specificity — meaning it generates a lot of false positives (patients who have a high PSA but don't have cancer) said Lu.

By contrast, the test devised by his group, named Parsortix, measures levels of CTCs. It has high specificity, meaning it can accurately identify true "negative" results because no tumor cells are shed if no cancer is present. The Parsortix test alone, he said, could spare 90% of men from unnecessary biopsy. The downside is that, because not all prostate cancers shed tumor cells, the CTC test is less sensitive, so up to 23% of men who have prostate cancer could be missed using the new CTC test alone.  

The London team calculated how accurate their test was when combined with existing measures such as PSA, as well as a proprietary 12-gene panel from a blood sample. When the team combined the results of CTC, PSA, the gene panel, and MRI they calculated they would be able to avoid 42% of unnecessary biopsies and identify 100% of clinically significant cancers.

The only currently available CTC liquid biopsy for prognosis in prostate cancer, the Cellsearch CTC test, was approved by the US Food and Drug Administration in 2008 for metastatic prostate cancer. Lu said his test is the first CTC test that is effective before a patient undergoes a biopsy, thus potentially sparing men this procedure. Most CTC-based tests have around 80% specificity.

"It's not surprising that we could do better, but how much better we had no idea before the experiment," he said. "It's exciting. We thought it would be similar [to the others], around 80%, but it's good that we got this high accuracy — it's a big discovery."

The key, said Lu, is that CTC is used in combination with other existing measures such as PSA and MRI to boost the results.

"Each of [our measures] by themselves does not perform that well, but when combined, when one has sensitivity and one has specificity, the accuracy increases dramatically," he summarized.

The study was supported in part by ANGLE, which holds the marketing rights for the Parsortix system. One author has reported working as a medical consultant for ANGLE. The other authors have reported no relevant financial relationships.

J Urol. Published online August 7, 2019. Abstract

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