Tom Keane: Hello, everybody. This is Tom Keane, coming to you from UroToday. I'm actually going to discuss a presentation, which took place at the SIU in 2019. This was an extremely interesting presentation, and it's very topical. It was entitled, Developments in Imaging Prior to Biopsy in Prostate Cancer, Are Systematic Biopsies Still Required?. This presentation was delivered by Dr. Laurence Klotz, who I'm sure doesn't need any introduction. He's a Canadian who works in Montreal. He is one of the people who founded active surveillance. And I'm delighted to say, is a good pal of mine.

He discussed the recent developments in imaging prior to prostate biopsy and pointed out that with Gleason grade group 1, the goal obviously is to identify the presence of higher-grade cancer. However, with Gleason grade 2, that triggers or has triggers for intervention that are not quite so obvious.

Now, in the Lancet in 2017, the PROMIS study was published and it was a landmark trial showing the superior accuracy of MRI compared to the transrectal biopsy alone. In this trial there were 576 men who underwent a 1.5 Tesla MRI study with systematic and template mapping biopsy. 40% had clinically significant prostate cancer. This showed that MRI had a negative predictive value and a sensitivity of 76% and 88% respectively. Since then, there've been many additional studies assessing the effectiveness of MRI in detecting and ruling out clinically significant cancer, which is really what we want to do. And he presented a slide at that time, which basically looked at 13 trials. These were randomized MRI studies comparing systematic biopsies versus MRI-targeted biopsies. Now the numbers ranged in these trials from 54 patients to 1140 patients. And again, the cancer detection rates varied from 34 to 100%, sensitivities varied from 58 to 96% depending on the study, and specificity from 23 to 94%. So pretty much it depended on which study you were looking at and how well the study was performed.

Now since then, there have been many additional studies assessing the effectiveness of MRI and detecting and ruling out clinically significant cancer. And table one, which he also presented, showed a negative predictive value ranging from 79 to 100%. There've also been a few randomized controlled studies comparing systematic biopsies and MRI targeted biopsies, showing an advantage to the targeted biopsies. This was presented in table two, which I know we will have up on the site.

In essence, the negative predictive value of the MRI is a function of the underlying risk. For a 30% risk of prostate cancer, the negative predictive value is 88%. While for 60% risk, The negative predicted value is 67%. In the landmark randomized prospective controlled study, the PRECISION study, the MRI informed targeted biopsy diagnosed 38% of clinically significant cancers compared to only 26% diagnosed by the systematic biopsies. And figure one summarized the percentage of clinically significant, clinically insignificant, and no cancer stratified by PI-RADS 2 MRI findings in the PRECISION trial.

In the recently published ASIST trial, which was led by Dr. Klotz, all undiagnosed or untreated patients had an MRI at two years. The upgrading rate to a Gleason group 2 or above was 27% in the systematic biopsy, and 13% in the MRI and systematic biopsy arm. This gave a hazard ratio of 0.62 with a P-value of 0.056. Dr. Klotz concluded in this trial that despite seeing no difference in upgrading at the initial biopsy, patients on the MRI arm had a lower risk of subsequent upgrading.

According to Dr. Klotz, there's no doubt that MRI and targeted biopsies confer an improvement in the diagnosis rate of clinically significant prostate cancer when compared to systematic biopsies. However, the negative predictive value for MRI has been shown to be lower than had originally been hoped at around 85%.

The general consensus that is being developed is that if the risk of high-grade cancer is lower than 10%, it might be safe to omit systematic biopsies, otherwise, they are necessary. In men with an elevated PSA, deciding what is the correct next step, be it MRI or biomarker, is largely a function of resources, cost, availability and patient preference. Dr. Klotz also discussed the ideal number of cores that need to be taken for each target. It would seem that the magic number is currently three cores per target.

Additional concerns about relying on MRI and only targeted biopsies are, number one, intraductal cancer and cribriform pattern are both associated with aggressive disease and appear to be less conspicuous on MRI to date. Number two, fusion-targeted biopsies have a learning curve, and the negative-targeted biopsy can be due to a miss, which then goes ahead to provide false reassurance to the patients. Dr. Klotz concluded his talk stating the main limitations of MRI, which include its lack of real-time interaction, the requirement of a radiologist, the risk of not capturing small satellite lesions, and underestimation of the lesion volume. Additional limitations may include the cost and complexity of MRI and the associated patient anxiety.

This, therefore, leads us to ask whether there are any alternatives to MRI. And more recently one of the most interesting and currently available alternatives to MRI is the high-resolution micro-ultrasound. It uses exact 29 megahertz compared to the conventional ultrasound, which uses a six to nine megahertz. The resolution is also improved with 70 microns. It has a similar footprint and cost as conventional ultrasound with a short learning curve. It uses the prostate risk identification using micro-ultrasound, our PRI-MUS protocol, which is like the PI-RADS protocol. And there's a figure, it's figure two, which will also be on the site, which can allow the listener, and hopefully, the viewer, to actually look at examples of the PRI-MUS protocol. It has been shown to have comparable sensitivity of MRI, and many publications assessing its utility will be coming out in the near future.

This was an extremely interesting presentation by Dr. Klotz. He went through a lot of the pitfalls and a lot of the current controversies, which surround assessing the degree of prostate cancer for patients who are considering active surveillance or who may require more aggressive therapy. I look forward to talking to you again in the near future. Keep an ear out. Bye-bye.