Impact of long-term androgen deprivation therapy on PSMA ligand
PET/CT in patients with castration-sensitive prostate cancer
Abstract
Purpose: Since the introduction of PSMA PET/CT with
68 Ga-PSMA-11, this modality for imaging prostate cancer (PC) has spread worldwide. Preclinical studies have demonstrated that short-term androgen deprivation therapy (ADT) can significantly increase PSMA expression on PC cells. Additionally, retrospective clinical data in large patient cohorts suggest a positive association between ongoing ADT and a pathological PSMA PET/CT scan. The present evaluation was conducted to further analyse the influence of long-term ADT on PSMA PET/CT findings.
Methods: A retrospective analysis was performed of all 1,704 patients who underwent a
68 Ga-PSMA-11 PET/CT scan at our institution from 2011 to 2017 to detect PC. Of 306 patients scanned at least twice, 10 had started and continued ADT with a continuous clinical response between the two PSMA PET/CT scans. These ten patients were included in the current analysis which compared the tracer uptake intensity and volume of PC lesions on PSMA PET/CT before and during ongoing ADT.
Results: Overall, 31 PC lesions were visible in all ten patients before initiation of ADT. However, during ongoing ADT (duration42–369 days, median 230 days), only 14 lesions were visible in eight of the ten patients. The average tracer uptake values decreased in 71% and increased in 12.9% of the PC lesions. Of all lesions, 33.3% were still visible in six patients with a completePSA response (≤0.1 ng/ml).
Conclusion: Continuous long-term ADT significantly reduces the visibility of castration-sensitive PC on PSMA PET/CT. If the objective is visualization of the maximum possible extent of disease, we recommend referring patients for PSMA PET/CT before
starting ADT.
Question: Does long-term use of androgen deprivation therapy (ADT) make prostate cancer lesions difficult or impossible to see on some imaging scans, even in tumors that continue to grow?
Written by
Kuanyin
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Here's the problem. I have a low-volume tumor load which tends to create a false sense of security. I fell into this "snare" once before, when after a period of a very stable relatively low PSA, a PET/CT scan showed my tumor had upped its game. Now, even though I really don't like it, I have this scan every two years. My oncologist doesn't want us to get caught sleeping again.
Three of my docs recommended that I wait until my PSA was close to 1.0 before getting the 68Ga-PSMA-11-PET/CT scan. Even then it did not identify all the LNs that were involved. The scan identified 3 sacral LNs...8 were removed robotically and 5 had evidence of PCa metastases per the path report. The surgeon removed those additional 5 since he felt that they appeared suspicious. By the time my surgery took place my PSA had reached 1.2. My one month post-op PSA had dropped to 0.54 which obviously meant that I still had stuff going on.
I fully understand the point that you are making...I too questioned the validity of the surgery. However, I believe that it may have bought me some time since I have been dreading the thought of Lupron and other forms of ADT. My last PSA 13 months post-op was 0.49.
Your post answered a concern that I had prior to subjecting myself to the 68Ga-PSMA-11 scan and subsequent sacral LN surgery. It is my understanding that this scan and the 18F-DCFPyL are the most sensitive scans currently available (please correct me if I'm wrong) and both require a PSA to be in the vicinity 0.7 before their validity is of any consequence. Based on what you have stated, "mets that are under 4 mm" will most likely not show up on these scans; therefore, these scans in many cases such as in mine are a waste of money and time. Your statement, "Lowering PSA by taking out larger mets doesn't solve the problem of systemic mets - ADT does." would also negate the usefulness of these scans when prescribed for metastatic recurrence after an RP. Based on this information, most of us should just 'submit' (pardon what may sound like a facetious comment) ourselves to ADT when biochemical failure becomes evident. Regarding your "Tamoxifen" recommendation for gynecomastia, I am having a difficult time finding it in Thailand...wonder why? Thank you for your valuable input on this forum...your knowledge of PCa is quite impressive!
I want to make clear that I am not against metastasis-directed therapy - I'm just saying the evidence is inadequate at this time to support it. There is, however, sufficient evidence that systemic therapy is beneficial. So it doesn't make sense to me to withhold systemic therapy in order for PSA to rise so that mets become detectable - it seems like a self-fulfilling prophecy.
I can't imagine that tamoxifen is unavailable in Thailand. It is part of the worldwide standard of care for breast cancer; it is relatively inexpensive. Raloxifine can be used instead, but it is more expensive.
Thanks Allen! I agree with your comments. Great link!
I haven't been able to find raloxifine either...this does seem strange since we have most Western World drugs available here; many at very low prices and some prescription drugs available OTC. The Oestrogel for example is less than $9.00 here...$55 in Canada. Triple antiretroviral HIV drugs (one pill/day) are $1.00/month for Thai people and I believe that the drug is also available to foreigners for around $30/month.
To the best of my understanding, the additional five LNs that were removed were 'adjacent' to the three identified on the scan. The three identified were in close proximity to each other. I was also told that because of the magnification during robotic surgery, it was possible to see slight abnormalities which caused suspicion.
When one pelvic LN is involved, as caught on a PET scan, there are likely many more. We don't have any really good means of finding all the LNs involved:
With PSMA-based PET scans, those who had ADT in the last 6 months had higher detection rates (92%) compared to those who'd had no ADT recently (78%). This may be because those who had ADT recently had more advanced tumors. There was some early evidence in mice and lab studies that ADT upregulated PSMA. One clinical study indicated that ADT improved detection of PSMA. Two studies showed no effect of ADT on PSMA detection. More recent evidence indicates use of ADT negatively impacts detection rates. The patient should avoid ADT before getting a PSMA-based PET scan, if possible.
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