PSMA expression & Survival in advanced PCa treated by 177 Lu-PSMA-617 Radioligand Therapy

[pjoshea13]

Interesting new German study below [1].

***

The terms used below are:

PSMAaverage ... lowPSMAaverage ... highPSMAaverage

PSAmin ... lowPSMAmin ... highPSMAmin

PSMAmax

***

"PSMAaverage was a significant prognosticator of overall survival in contrast to PSMAmax (HR: 0.959 ... vs. HR: 0.992 ...).

"Patients with low average PSMA expression (lowPSMAaverage) had significantly shorter survival compared to those with high average expression (highPSMAaverage) (5.3 vs. 15.1 months ... HR: 3.738 ...).

"Patients with low PSMA expressing metastases (lowPSMAmin) had shorter survival compared to those without a low PSMA expressing metastasis (highPSMAmin) ... 7.9 months vs. 21.3; HR: 4.303, ...).

"Patients that were classified as highPSMAaverage but with lowPSMAmin had an intermediate overall survival (11.4 months; longer compared to lowPSMAaverage, 5.3 months ... but shorter compared to highPSMAmin, 21.3 months ...)."

-Patrick

[For more detail, send me a private message.]

[1] pubmed.ncbi.nlm.nih.gov/326...

Theranostics

. 2020 Jun 19;10(17):7812-7820. doi: 10.7150/thno.47251. eCollection 2020.

Analysis of PSMA expression and outcome in patients with advanced Prostate Cancer receiving 177 Lu-PSMA-617 Radioligand Therapy

Robert Seifert 1 2 3 4 , Konstantin Seitzer 1 4 5 , Ken Herrmann 2 3 4 , Katharina Kessel 1 , Michael Schäfers 1 4 , Jens Kleesiek 3 6 , Matthias Weckesser 1 4 , Martin Boegemann 4 5 , Kambiz Rahbar 1 4

Affiliations collapse

Affiliations

1 Department of Nuclear Medicine, University Hospital Münster, Münster, Germany.

2 Department of Nuclear Medicine, University Hospital Essen, Essen, Germany.

3 German Cancer Consortium (DKTK).

4 West German Cancer Center.

5 Department of Urology, University Hospital Münster, Münster, Germany.

6 Division of Radiology, German Cancer Research Center, Heidelberg, Germany.

PMID: 32685021 PMCID: PMC7359095 DOI: 10.7150/thno.47251

Abstract

Rationale: PSMA-PET-CT enables measuring molecular expression of prostate-specific membrane antigen (PSMA) in vivo, which is the target molecule of 177Lu-PSMA-617 (Lu-PSMA) therapy. However, the correlation of PSMA expression and overall survival (OS) in patients treated with Lu-PSMA therapy is currently unclear; especially with regard to coexistence of high and low PSMA expressing metastases. To this end, this retrospective single arm study elucidates the correlation of PSMA expression and overall survival in patients treated with Lu-PSMA therapy. Additionally, PET based criteria to define low PSMA expression were explored. Methods: Eighty-five patients referred to Lu-PSMA therapy were included in the analysis. Pretherapeutic 68Ga-PSMA-PET-CT scans were available for all patients. SUVmax of the highest PSMA expressing metastasis (PSMAmax), SUVmax of the lowest PSMA expressing metastasis (PSMAmin), and average SUVmax of all metastases (PSMAaverage) amongst other PET parameters were measured for each patient. A log-rank cutoff-finder was used to determine low (lowPSMAaverage) and high (highPSMAaverage) average PSMA expression as well as low (lowPSMAmin) and high (highPSMAmin) minimal PSMA expression. Results: PSMAaverage was a significant prognosticator of overall survival in contrast to PSMAmax (HR: 0.959; p = 0.047 vs. HR: 0.992; p = 0.231). Optimal log rank cut-offs were: PSMAaverage = 14.3; PSMAmin = 10.2. Patients with low average PSMA expression (lowPSMAaverage) had significantly shorter survival compared to those with high average expression (highPSMAaverage) (5.3 vs. 15.1 months; p < 0.001; HR: 3.738, 95%CI = 1.953-7.154; p < 0.001). Patients with low PSMA expressing metastases (lowPSMAmin) had shorter survival compared to those without a low PSMA expressing metastasis (highPSMAmin) (p = 0.003; 7.9 months vs. 21.3; HR: 4.303, 95%CI = 1.521-12.178; p = 0.006). Patients that were classified as highPSMAaverage but with lowPSMAmin had an intermediate overall survival (11.4 months; longer compared to lowPSMAaverage, 5.3 months, p = 0.002; but shorter compared to highPSMAmin, 21.3 months, p = 0.02). Conclusion: Low average PSMA expression is a negative prognosticator of overall survival. Absence of low PSMA expressing metastases is associated with best overall survival and the maximum PSMA expression seems not suited to prognosticate overall survival. Low PSMA expression might therefore be a negative prognosticator for the outcome of patients treated with Lu-PSMA therapy. Future studies are warranted to elucidate the degree of low PSMA expression tolerable for Lu-PSMA therapy.

Keywords: PSMA PET; PSMA radioligand therapy; prognosticator; prostate cancer.

© The author(s).

[GP24]

In the study they mention: "the correlation of PSMA expression and overall survival (OS) in patients treated with Lu-PSMA therapy is currently unclear". So this applied to patients treated with Lu-PSMA therapy only. I think it is not suprising that patients with a high PSMA expression have better results when getting a Lu-PSMA therapy.

[pjoshea13 in reply to GP24]

But it's useful for the potential patient to have such benefit quantified.

-Patrick

[dvcarola2]

Hi Patrick, thank you for your post. These are the SUVs i saw from my husband’s last 18F-FPSMA-1007 Pet/Ct before he did his 1st Lu-177:

1.) SUV 60.7 in the posterior urinary bladder wall

2.) SUV 107.9 in the lymph nodes in the pararectal, presacral, bilateral illiac chains

3.) SUV 37.9 in the osseous lesions (ribs, vertebrae)

How should I interpret these SUVs based on your post? Thank you!

[pjoshea13 in reply to dvcarola2]

Perhaps this will help (from the full text):

Median of the highest value of all patients:

SUV-max 44.6 (7.1-181.6]

SUV -mean 29.5 [4.6-129.8]

SUV-peak 31.6 [4.7-159.7]

In contrast, the Median of the average value of all patients: 18.9, 13.0, 12.1.

This suggests to me that he is a very good candidate for treatment.

(I should point out that I am totally unqualified to advise you, etc.)

-Patrick

[dvcarola2 in reply to pjoshea13]

Hoping you are right Patrick. Im also praying that he will respond to Lu-177 given that he has very high SUVs but we will not know for sure until we do the PSMA pet/ct after 2nd infusion in Sept. I will keep you posted. Thanks!