Imaging and pathology: The harm of false positives

16 November 2019

“A false positive can really change the life of a patient so we should only make a diagnosis if we are 100% certain,” said Prof. Harriet Thoeny (Bern, CH) at EMUC19 on Saturday. Prof. Thoeny was co-chairing a session on the clinical impact of false positives in uro-oncology. It included presentations on false positives with PSMA-PET, MRI of the prostate and in pathology.

The speakers gave several examples of mimicking of PCa or of bone metastasis, or the grey areas within a PI-RADS scoring. Their talks gave the assembled urologists and oncology specialists a good idea of the possible false positives that have to be ruled out before any conclusions can be drawn from imaging or pathology. Following the session, we spoke to Prof. Thoeny about the topic, particularly what specialists can and should do in the case of a false positive.

Always consider the complete picture

Prof. Thoeny recommends looking at the whole history. “When it comes to PCa, always look at the morphology. But also the available clinical data, like the PSA. If there is a discrepancy (for instance a low PSA but a lot of metastasis), if there is a minimal doubt, you have to perform a biopsy to prove your theory. Chemo and hormone therapy have a huge impact on the patient and should be avoided if possible.”

“It is very difficult to draw conclusions on metastasis based PSMA-PET. I know that there is a lot of enthusiasm for the technology and it is sometimes considered to be the holy grail, but it’s not.”

Is imaging only suitable in combination with other methods? “No, I think MRI of the prostate, this is the way to go,” said Thoeny. “Of course you need extra training but I agree…”

The PI-RADS scale of course also has scope for false positives. “The difficult ones are PI-RADS 3, because you’re not sure how to proceed. Taking the PSA density into account can help you rule out false positives. There are plenty of calculators online. There is a cut-off of 0.12ng/ml. If it’s higher than 0.12, then it’s more aggressive, and if it’s lower we do a follow-up.”

A friend of a friend

Prof. Thoeny related a recent case she was involved in around two years ago, a friend of a friend in his early 50s. “His Gleason score was determined to be 6-8 following a biopsy. He went to have a PSMA-PET done. I hadn’t heard from him in a while. He later told me that he was told that he had bone metastasis and lymph node metastasis. They had said ‘Surgery can’t help you. You will get hormonal and radiotherapy, and possibly chemo. You have another 3-4 years left to live.’ He was in an intense shock. He walked out of the clinic and thought to himself: ‘I hope I’ll have a car accident,’ he didn’t want to live anymore.”

“The specialists had looked at morphology, and it looked really suspicious on the images. This seemed odd to me, considering that he had a stable PSA for 5 years. I asked him to send me all the images of the previous years. I went back and looked at the old MRIs, and you could tell that the bone lesions were there already 5 years ago. I told him: undergo surgery, have a lymph node dissection done. They were all negative. He’s now happy and in good shape.”

“We have no idea what caused the false positive, it’s still a mystery. There’s a lesson for today’s audience: if the whole story doesn’t fit together, you should be more critical. In the case of PSMA-PET, you should have a biopsy for confirmation before undergoing the extremely impactful systematic treatments. In the case of a prostate MRI, if you take PSA density into account, follow-up should be enough.”