Non-invasive accurate blood test for prostate cancer

For men, one of the most dreaded moments could be hearing, “We’re not yet sure, but your PSA is high; you’ll have to come for further tests.” This could start a chain of events which ends in the diagnosis of prostate cancer - including a prostate biopsy, and ending in a major surgery for prostate removal. And after all this, the cancer often turns out to be a very slow-growing tumor that could have well been left alone, even while some patients suffer complications from the biopsy and/or surgery. This could all change with a new simple but highly accurate blood test that actually detects prostate cancers which need treatment, and nothing else.

The new test only requires a blood sample, which is much less invasive than a biopsy. Yet scientists predict that it will complement the test in current use, called the prostate-specific antigen (PSA) test, enabling doctors to diagnose aggressive prostate cancer correctly in 90% of test-positive patients, without having to do biopsies. It can thus avoid over-diagnosis and over-treatment of this condition.

By enabling accurate and early diagnosis, this test could help immensely to bring down the suffering due to prostate cancer which is the most common malignancy in men in developed countries. Each year, it gives rise to 1.3 million cases all over the world.

What is the PSA test?

The PSA test looks at levels of an antigen present on prostate cells, a protein which could be secreted at high levels not just because of cancer in the prostate but also inflammation or benign growths.

When the PSA level in the blood rises abnormally, a biopsy is taken from the prostate gland from several sites. This involves surgery, with associated risks of bleeding and infection. The PSA test can help diagnose the cancer early, but the number of false positives is high, leading to unnecessary biopsies in about 75% of cases. This means the specificity is low.

Not only so, even the positive biopsies include many low-grade or early prostate cancers that are extremely slow-growing and will not result in the patient’s death even if left untreated.

What does the new test do?

In contrast, the new test (called the Parsortix® system) is designed to pick up early cancer cells in the bloodstream which have dropped off the original tumor. These are called circulating tumor cells (CTCs), and are obviously specific for prostate cancer. When these are found in conjunction with a high PSA, the chances of a right diagnosis are much higher.

In fact, the study tested the accuracy of prediction in over 250 patients with prostate cancer, of which 98 had not undergone a biopsy. The remaining 155 had just received a diagnosis of prostate cancer. With the new test, researchers found CTCs in 184 patients. In terms of groups, CTCs were found in 54% of patients with diagnosed localized prostate cancer, and their presence accurately predicted aggressive prostate cancer that required treatment.

In the other group that had not undergone biopsy yet, the CTC test in tandem with PSA achieved a high prediction rate of almost 90% for aggressive prostate cancer. Scientists were also able to pick out 12 genes that predicted this tumor behavior. When both tests were used together with the 12-gene panel, aggressive cancers could be predicted with an incredible accuracy of 92%, far better than any biomarker test reported to date.

When MRI was used alone to diagnose aggressive prostate cancer, the prediction rate was 62%, but when these tests (CTC, PSA and 12-gene panel), a 93% accuracy was achieved. Moreover, an analysis of the number and types of CTCs in the blood also reflected the tumor’s behavior as later proved by biopsy results.

What do the results tell us?

The benefit of accurate prediction of aggressiveness with respect to this tumor is obvious: since non-aggressive tumors often need no treatment at all except for careful monitoring, being able to focus on only aggressive tumors will mean that a lot of benign and low-grade tumors will not be unnecessarily picked up or treated. This will prevent a lot of diagnosis-related stress, many biopsy-related harmful effects, and overtreatment of many tumors.

Thus researcher Yong-Jie Lu says, “Testing for circulating tumour cells [has the] potential to improve the current standard of care. By combining the new CTC analysis with the current PSA test, we were able to detect prostate cancer with the highest level of accuracy ever seen in any biomarker test. This could lead to a paradigm shift in the way we diagnose prostate cancer.”

These initial results from patients at a single center will need to be replicated in a larger multicentre trial, following which it could become part of the current treatment protocol. This could take another 3-5 years, similar to the probable time required for clearance by the US Food and Drug Administration (FDA).

The research was published in the Journal of Urology on August 7, 2019.

Journal reference:

Non-invasive detection of clinically significant prostate cancer using circulating tumor cells. Lei Xu, Xueying Mao, Alistair Grey, Glenda Scandura, Tianyu Guo, Edwina Burke, Jacek Marzec, Semah Abdu, Elzbieta Stankiewicz, Caitlin R. Davies, Prabhakar Rajan, Karen Tipples, John Hines, Pui Ying Chan, Diane Campbell, Karen Wilkinson, Sakunthala Kudahetti, Jonathan Shamash, Tim Oliver, Daniel Berney, Greg Shaw, and Yong-Jie Lu. Journal of Urology, https://www.auajournals.org/doi/10.1097/JU.0000000000000475