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Wayne Brisbane: Hello. Thanks to the organizers for the opportunity. Wayne Brisbane, assistant professor of urology here. This work was largely led by Jeremie and funded by Johannes. So I have the great opportunity to present it. And specifically, it's "Can PSMA-Targeted Prostate Biopsy Detect Cancer When an MRI-Guided Biopsy is Negative?" A couple of disclosures, which are not relevant to the talk.

So introduction. As Dr. Raymond mentioned, MRI-guided biopsy is the standard of care. It works great. But we do know that MRI is not perfect. I used a conservative number, 7% to 12% of cases for clinically significant prostate cancer can be missed. And this can be due to invisibility or just technical error.

So here's just a quick case presentation to whet the appetite for the clinical scenario: a 71-year-old male, active surveillance, had a biopsy that was benign in 2009, again in 2012 had a TURP that was benign, and then had some low-grade disease in 2013. It just didn't seem to match up.

His PSA, as you see, goes from 2.6 to 8.5. This was in 2017, but this work was done in 2017-- or 2016—so earlier on in our PSMA experience. But basically, we took the MRI, overlaid the PSMA lesion, and found that he did, in fact, have 3+4 prostate cancer, a relatively large lesion anteriorly.

So we designed here a phase I trial, and this was to assess the detection rate of Grade Group 2 or greater prostate cancer with the gallium PSMA following benign or discordant biopsy, which we defined as low volume—1 to 2 millimeters of 3+3 that just doesn't work well, but you have a PSA density that's too high.

So this was the outline. You’d have an MRI-guided biopsy—again, benign or low-volume Grade Group 1 disease but PSA density is high—or you had a PI-RADS 4 or above lesion, or there was just a discordance there. And then they would get a PSMA PET/CT scan and then go to biopsy based on that.

This is the breakdown. We had a PSMA PET/CT. About 70 patients were screened. We didn’t biopsy everyone. If they had an SUV max greater than 3, they would go to biopsy. If it was less than 3, they would go to observation.

How this was done from a technical standpoint: we would have this CT/PET, Jeremie did the difficult task of contouring the prostate based on the CT, and then we fused this to ultrasound done by the conventional approach that we do quite often with MRI.

This is the baseline for patients, but you will see that it’s pretty similar to men you’d expect to have prostate cancer—age around 64, PSA density a little higher, as we mentioned. The majority of patients had a benign biopsy, a few with Grade Group 1, and there’s the distribution of their PI-RADS. Most patients had an invisible lesion.

This is the 39 patients that had an SUV greater than 3. You’ll see about 16 of them had benign results even after follow-up biopsy—so that’s their second biopsy. Seven of them had Grade Group 1, and 16 had Grade Group 2 or greater. So that’s our primary outcome—41% detection of Grade Group 2 on the PSMA-guided biopsy.

When you break down the grade groups, these are cancers that you probably don’t want to miss. Six of them are Grade Group 2, but another 10 of them, as you can see broken down there, are Grade Group 3, 4, and 5 respectively.

Of those patients with the 16 Grade Group 2 or greater, five overlaid the prior MRI lesion—meaning there was a miss—but there were 11 de novo lesions.

When we look specifically at the MRI-concordant PSMA lesions—so these are the lesions that overlap the prior MRI—there was a similar distribution between your MRI and PSMA cancer-containing ROIs. There were five of them, about 33% anterior and 22% posterior.

However, more interesting, in my opinion, is when you have an MRI-discordant or de novo PSMA ROI. It was almost three times more cancer in anterior de novo regions of interest. So looking at this, that bottom row—27%, or eight patients—had a new anterior lesion that was invisible in MRI, and about three patients with posterior. And these were the cancer-containing ROIs.

When we look at the MRI-discordant or de novo PSMA ROIs and look at what SUV max threshold we can use, we screen-failed almost 30 patients. So that’s kind of an expensive way to run a trial. When we go forward, how can we use a different SUV max in order to inform our screening criteria?

We found that an SUV max less than 7 missed about three patients. And because these were very interesting—we have small numbers, not meaning to turn this into a case study—but I broke all of these patients down. So these are the patients you’re going to miss with an SUV max less than 7.

Two of those patients had very low-volume but clinically significant cancer—so 1 millimeter of 4+3 and that was an SUV max of 3.6, or 2 millimeters of 3+4 and that was an SUV max of 6.

However, there is one patient that you just are going to miss: the SUV max of 4.5 but 13 millimeters of cancer with cribriforming feature. Interestingly enough, the Decipher was low risk.

All of these cut points do have very similar AUCs. And I’m sure many in the audience are going to be very interested in how does the primary score correlate—it correlates quite nicely. So SUV max or primary score can be used. We report out both, but a lot of the analysis was done with SUV max. Interestingly, when you look at baseline PI-RADS and PSA density, this did not find significance in influencing the actual cancer detection.

So in conclusion, following a negative MRI-guided biopsy, PSMA provides a very important second look. This can be used for risk stratification. So future studies may consider using an SUV max less or equal to 7 to find most of the significant cancers—and I gave you the caveats previously.

This is the only tool that provides both a second look and novel anatomic information. Both saying 28% (11 of 39) are de novo Grade Group 2 lesions, and 12.8% missed MRI-positive lesions. I think this is a prime area for future evaluation because these new anatomic looks and risk stratification are not currently available in any other tools. Thank you.