Key opinion leaders review the OSPREY clinical trial studying PSMA PET scans for prostate cancer imaging.
Neal Shore, MD, FACS: We’ve reviewed a few of these alternatives and recognizing now that Gallium F-18, a PSMA [prostate specific membrane antigen] PET [positron emission tomography], and various other iterations are the state-of-the-art scan. It would be great Michael if you and Larry as well, can describe the OSPREY trial, which was a pivotal study that helped. Michael you were saying earlier, [it] led to the subsequent FDA approval for the 18 F PyL.
Michael Gorin, MD: The OSPREY trial had 2 arms to it. It had what they called cohort A and cohort B. Cohort A were men who had high-risk prostate cancer who were otherwise planned already to undergo a radical prostatectomy with pelvic lymph node dissection. These patients were imaged with DCF [docetaxel, cisplatin, and 5-fluorouracil] PyL PET CT prior to surgery. The surgeons and the patients did not learn the results of the scan and they proceeded with surgery as was planned. And because the prostate came out along with the lymph nodes, that allowed for calculations of both sensitivity and specificity. And we know that based on conventional imaging, all of these patients were N0 essentially. There were a few patients who were N1 who came in but most patients on the basis of conventional imaging were N0. And the presumption of that from the get-go is that there’s a fair percentage these patients, somewhere in the order of 20-30% who had pathologic analysis are going to have lymph node metastases under the microscope. And the question was whether or not DCF PyL afforded the additional sensitivity necessary to pick up those metastases. And, because you had the lymph node packet right there, you could figure out whether or not the scan was specific or were there false positives in these packets. And that was the primary endpoint of cohort A and we’ll talk about the results in just a moment. Then there was cohort B. Cohort B was an interesting cohort and you must think about it in the context of the time in which the study was planned. This was the first trial that was put forth to the FDA for approval of the imaging agent. And the FDA wanted to establish was PSMA even being taken up by metastatic prostate cancer or is it possible there was lots of false positives out there? Cohort B was designed with patients with widespread metastatic disease for them to undergo PyL imaging and then subsequently a biopsy of their metastatic sites. And that was to prove that these were sites of prostate cancer that were taking up the radiotracer and not just falsely positive for some other reason. And it also allowed for what comparisons of the sensitivity of the test relative to conventional imaging where some sites of disease were seen. That’s how we knew the patient had metastatic disease but how much more, what’s the level of concordance between the PSMA PET scan and what was seen on conventional imaging? Now, it’s a foregone conclusion that PSMA is taken up by prostate cancer and virtually only prostate cancer with some exceptions that are born out. At the time that the cohort view was put forth, we needed to still prove that.
Neal Shore, MD, FACS: Any thoughts about the baseline characteristics? You did a great job of summarizing the differences in the 2 cohorts.
Michael Gorin, MD: Yes. Only 3% of patients were known based on conventional imaging to have lymph node positivity and virtually none of the patients, less than 1%, maybe 1% only, of patients had metastatic disease who were scheduled to undergo radical prostatectomy. Virtually, all the patients in this trial were truly NCCN [National Comprehensive Cancer Network] high-risk on the base of the standard of care imaging at the time.
Neal Shore, MD, FACS: Yes. It’s a great study. And let’s have you and Larry when you were getting this for the first time, you had the readout before the publication. It had to be quite gratifying to see these findings.
Michael Gorin, MD: The specificity was exactly as we would hope for, we see just a tremendous degree of specificity north of 95% in these analyses. The sensitivity, though, was a bit lower than the primary endpoint was set to at the initial design of the study. And we came in at 38%. And the way that the calls were established was based on 3 blinded readers who read the scans and they took the composite, the average sensitivity across those readers. There is a range here to this 38%, but ultimately, they came in at 38%, which again, didn't meet the primary end point, the number that they had set out to achieve. But still, when you think about it, all those patients were thought to have no lymph node disease. And now, 40% of patients prior to going to the OR [operating room] we were able to pick out that they had known metastatic disease. Then, in a secondary analysis, we wanted to see whether, if you limited, if you restricted this to just patients whose lymph nodes on pathology were greater than a half-centimeter, what was the sensitivity in them? And upon doing that, sensitivity goes up to 60%. And in the post-hoc analysis, we reason that this was a more fair analysis from the get-go because a lymph node could have as few as just a handful of prostate cancer cells. And if a pathologist detects them, that’s N1 disease where it’s completely unreasonable to think that a PET scan would ever be able to pick up those patients. With that said, whoever, a CT scan requires a lymph node to be north of a centimeter and a half, if you will, for being able to be detected and read out as a lymph node metastasis. Here in this post-hoc analysis, we set the bar quite high for achievement at as little as 5 ml but also balances the realistic nature of what one could expect from an imaging test. And again, we see the number almost doubled it, around 60%.
Neal Shore, MD, FACS: I like that feature, especially as we keep in mind that historically, no matter how sophisticated the multi-slice CT scanner is, there is that threshold of 1 cm, and this was looking at a clearly sub-centimeter lymph nodes.
Lawrence Saperstein, MD: I just wanted to emphasize that was a great summary, Mike and I could not possibly said it as eloquently, that’s really what’s impactful here when we’re talking about the threshold for conventional imaging. And as we’ll show in some of the examples, how exquisitely sensitive that DSMA PET CTs are seeing lymph nodes that are tiny. And that’s important to emphasize. Thanks.
Michael Gorin, MD: But one lesson that it absolutely teaches us though, is that we see that the sensitivity is only 40%. As we think about applying this modality to things like metastasis directive therapy in patients with oligometastatic prostate cancer, you still must imagine how much disease are we not seeing despite this very sensitive tool.
Neal Shore, MD, FACS: Right. We're not at the point where it’s 100% accurate and it's binary, right? If it’s negative, you don’t have disease. If it’s positive, you absolutely have disease.
Transcript edited for clarity.