No more false dawns: how fusion biopsies and new diagnostic pathways are ending the uncertainty of ‘false negatives’

Mr Alan Doherty

The most significant developments in my field recently have not been in how we treat prostate cancer, but what we do beforehand, to assess and understand the disease.

Six years ago, like all UK urologists, the prostate biopsy I commonly used was the TRUS (transrectal ultrasound-guided biopsy). It involves inserting 12 needles through the rectum into the prostate using ultrasound guidance to focus on the area of suspected cancer. Unsurprisingly, the TRUS method is known to carry a high risk of producing false negatives; cancer is not found in the biopsy samples, but cancer is present. We know, from a series of international studies, the false negative rate for TRUS can range from 11 per cent and can be as high as 50 per cent (PROMIS trial).

Prostate cancer is a multi-focal disease, which means there is no ‘lump’ and often not a single tumour, but sites of cancer located in different parts of the prostate. The access angle of the TRUS biopsy means it is difficult to reach all parts of the prostate, where cancer can occur. Why therefore is TRUS accepted in prostate cancer diagnostics? The argument was that if prostate cancer was clinically significant, it would be large enough to be found and if there was significant cause for concern (rising PSA), the biopsy could be repeated.

However, at BPC, we changed our diagnostic pathway which in turn defined our perspective on the TRUS. For several years, our process has been: following a raised PSA or suspicious digital rectal examination, the next step is a prostate MRI scan and a genetics based PCA3 test follows. Only after these steps do we proceed to a biopsy.

If an MRI has indicated prostate cancer and the PCA3 test is positive for risk of prostate cancer, a negative TRUS biopsy will not allay concerns. As a urologist, the question you ask yourself throughout the process is: am I reassured by this; is this sufficient? With the diagnostic pathway we developed at BPC, the TRUS was rendered insufficient; we would only proceed to biopsy with a strong indication of prostate cancer and as such, a negative result would only produce a concern about the test’s accuracy. In other words, TRUS is insufficient to ‘give closure’: for me to be confident to tell a patient – you don’t have cancer, go home and stop worrying.

The technology we regularly use at BPC is called an MRI fusion biopsy. With this method, before the biopsy, the radiologist maps out the prostate into a 2D contoured model which is then super-imposed with ultrasound (hence the term ‘fusion’). This means as I move my probe around the prostate to focus the biopsy needles, the areas of suspected abnormality light up in red. This is important because it enables us to biopsy in a far more accurate way (studies show accuracy of above 90 per cent).

For this reason, it is the diagnostic side of the prostate cancer field which currently stands out as the ‘cutting edge’ part of our field, with step changes that have transformed the way we measure and understand the disease.