Good morning Nathan
Great find.
What this study looks at is interesting in a number of ways, but I will focus on just the question of whether this has the potential to render 64Cu-Sar-bisPSMA obsolete or not.
For those with no time, the short answer is: NO, it does not.
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Here is the Long Answer (I base my analysis on just the info that I can access - the abstract);
FIRST - We need to understand the why, the what, and the how before trying to read their results.
BACKGROUND - KEY POINTSa) Low Sensitivity: The authors open up by emphasizing the low sensitivity that the currently used Ga68 PSMA tracers have in detecting Pelvic Lymph Node Metastasis (PLNM). The tracer they used is Ga68-PSMA-617, which is not Illuccix (Ga68-PSMA-11), but its similar.
b) Recognizing that part of the reason for the Low Sensitivity is the fact that some prostate cancers have low or no expression of PSMA, they hypothesise that targeting both the PSMA as well as another target, the Gastrin-Releasing Peptide receptor (GRPr), that is also found in some prostate cancers, may help.
c) What they refer to as 'dual targeting', seems like it was actually doing TWO separate tests: 68Ga-RM26 PET/CT and 68Ga-PSMA-617 PET/CT, one after another. What this may mean is that the patient got injected with Tracer 1 and had their scan (its Ga68 so it must be done within an hour), and went home, and then came back probably many days or weeks later to allow for complete washout and had an injection with Tracer 2, and had a scan again. This to me does not sound like dual anything - its one after another (serial) - but I do not have access to the full paper.
d) The study was prospective, in newly diagnosed yet untreated prostate cancer patients, who had this imaging and then had definitive therapy by way of radical prostatectomy and extended pelvic lymph node dissection. Standard of Truth Histopathology.
ANALYSIS PLAN
The authors basically combined the findings in order to decide how good this 'dual targeting' is, versus the Standard of Truth Histopathology!
# Negative / Negative = Negative
# Negative / Positive = Positive
# Positive / Negative = Positive
# Positive / Positive = Positive
RESULTSSince the report focus is on SENSITIVITY, only those patients that had POSITIVE Histopathology will be discussed, just as the authors did.
Test Sensitivity is the ability of a TEST to correctly identify patients with the disease (True +ve rate). In this case, its the % of positive imaging results amongst the patients confirmed to have metastatic cancer (positive nodes).
21 patients had positive Histopathology findings. Therefore, in the patients analysis, '
21' is the denominator. From that we can work backwards to deduce the exact numbers of POSITIVE PET/CT scans.
| PATIENT-BASED ANALYSIS | DENOMINATOR (HISTOLOGY +ve) | POSITIVE PET CT | SENSITIVITY |
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| 1 | 68Ga-PSMA-617 | 21 | 11 | 0.52 (52%) |
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| 2 | 68Ga-RM26 (GRPr targeting) | 21 | 10 | 0.43 (43%) |
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| 3 | DUAL TARGETING (COMBINED) | 21 | 16 | 0.76 (76%) |
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68Ga-PSMA-617 missed 10 out of 21 (these are false Negatives on this PSMA scan).
Out of these 10 that were negative on the PSMA scan - the GRPr scan detected 5, taking the positives to 16 (out of 21).
[I have left the lesion based Analysis as it is, in part an academic exercise, and in another part, a case of assessing volume of disease. The most important question here (in my view) is - has the cancer spread (metastasized - if it has, removing the prostate is inviting side effects for no gain.]
CONCLUSION
The combination of results from Ga68 PSMA tracer and a Ga68 GRPr tracer improved sensitivity from about 50% to 76%: That's an improvement from 50% missed cancer lesions down to 24% missed. Two scans is better than one! No problem!
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DISCUSSION
For context, what the results showed is that, if you take100 patients with proven metastatic disease with positive nodes), and you send them to these scans;
a) 68Ga-PSMA-617 will correctly return a positive in 52 (missing 48) while 68Ga-RM26 will correctly return a positive 43 (missing 57)
b) Using the results in combination (any positive), you will correctly identify 76 as having disease in the nodes and miss 24.
HOW DOES CLARITY COMPARE?
I do not have access to the full paper or its inclusion criteria - so I do not know if its comparable with Clarity or not. Also, the results we currently have from Clarity (COBRA) are for BCR - the preprostatectomy trial (CLARIFY) is still underway.
But since you asked, I shall proceed and assume you see enough similarities to justify a comparison.
KEY: Note that this study is equivalent to imaging the same patient with 64Cu-Sar-bisPSMA and then again with 64Cu-Sar-BOMBESIN (GRPr targeting), one after another.
Yes,
Clarity has a GRPr targeting tracer, and its the 64Cu-Sar-BOMBESIN (the subject of the SABRE Trial that is due to report within days to weeks)! SABRE(Phase 2) includes participants with PSMA-negative biochemical recurrence (BCR) of prostate cancer following definitive therapy, so its not the same group as the patients in this study.
Lets just do ONE test (one injection) and do one scan and see what we get! Lets go with the
JEWEL OF THE CROWN: 64Cu-Sar-bisPSMA! Remember - sensitivity requires
positive nodes as the denominator!
In COBRA, of the 9 patients who had biopsies, 7 were Lymph Node biopsies from areas outside of the Prostate fossa, and they were all positive. These 7 are the group that we can compare with the patients studied in this study (both because they are nodes like the cases studied in this study, and also because a sensitivity calculation requires positive histopathology).
Here is an updated table of results, now including 64Cu-Sar-bisPSMA results from the COBRA trial for comparison.
| PATIENT-BASED ANALYSIS | DENOMINATOR (HISTOLOGY +ve) | POSITIVE PET CT | SENSITIVITY |
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| 1 | 68Ga-PSMA-617 | 21 | 11 | 0.52 (52%) |
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| 2 | 68Ga-RM26 (GRPr targeting) | 21 | 10 | 0.43 (43%) |
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| 3 | DUAL TARGETING (COMBINED) | 21 | 16 | 0.76 (76%) |
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| 4 |
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| 5 | 64Cu-Sar-bisPSMA | 7 | 7 | 1.00 (100%) |
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IN ANSWER TO YOUR QUESTION
@nathan1984: If Superiority is going to cause the Inferior test to become obsolete, then it is the dual targeting as described that is headed that way. Its TWO scans for a 75% sensitivity, versus just one that surpasses those figures. I do not expect 100% in the larger CLARIFY trial though!
Thanks for your great question Nathan.
Have a happy Easter!
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SABRE TRIAL: 64Cu-SAR-BBN Positron Emission Tomography: A Phase 2 Study of Participants With PSMA-negative Biochemical Recurrence of Prostate Cancer
https://clinicaltrials.gov/study/NCT05407311https://jnm.snmjournals.org/content/early/2025/03/19/jnumed.124.269189https://www.claritypharmaceuticals.com/pipeline/sar-bbn/
(20min delay)