(UroToday.com) The 2022 GU ASCO Annual meeting included a prostate cancer session featuring work from Dr. Jones Nauseef and colleagues presented results of a quantitative assessment of PSMA imaging before and after 177Lu-PSMA-617 treatment in a Phase I/II trial. Dr. Nauseef’s group has previously reported a dose-intense single-cycle of 177Lu-PSMA-617 was effective in pretreated patients with mCRPC without requiring PSMA-positive imaging for enrollment. Prior posthoc analyses of these data using approximate quantification of exclusively the most PSMA-positive disease sites have demonstrated associations between PSA response and PFS with pre-treatment 68Ga-PSMA11-PET signal. Greater sophistication in pre-and post-treatment evaluation of PSMA-expression in tumor and normal organs may allow for better patient selection and prediction of toxicities.
There was a total of 50 patients treated on a phase I/II study of fractionated-dose (D1, 15) 177Lu-617-PSMA. Quantification using artificial intelligence (AI) was used to measure pre-and post-treatment PSMA signal intensity. Scoring cutoffs with confidence intervals around scan variation were empirically established from a subset of test/re-test of subjects within 24 hours without intervening therapy:
A variety of measurements were performed including SUVmean across all detectable tumor lesions, volume of lesions, and SUVtotal (Total + Volume), as well as select normal organs and changes after treatment. Associations with survival were tested via Cox proportional hazard models in univariate analyses and associations with adverse events and PSA responses were assessed via Wilcoxon rank sum tests.
There were 13 patients selected to complete AI-based quantification and associated survival analyses. Among these, 10 (77%) experienced any PSA decline, with 8 (62%) having PSA50 and 3 (23%) having PSA90:
The median overall survival (OS) was 17.0 months (95% CI 10, not reached) via Kaplan-Meier estimates. In univariate analysis, pretreatment SUVmean was associated with improved PFS (HR 0.66, 95% CI 0.49-0.90) and OS (HR 0.81, 95% CI 0.65-1.00). The metrics most strongly associated with PSA50 were pretreatment SUVmean (median 7.66 [IQR 6.52, 10.54] vs 3.50 [IQR 3.02, 3.56], p = 0.019) SUV Total (median 14982 [IQR 11110, 20595] vs 1303 [IQR 576, 1512], p = 0.019), change in Volume (-27 [IQR -44, -20] vs 145 [IQR 38, 154], p = 0.006), and SUVtotal (-57 [IQR -67, -35] vs 132 [IQR 9, 269], p = 0.030). Subjects with xerostomia had higher salivary gland SUVmax (pretreatment and change in after treatment), and those with pain flare had lower pretreatment SUV scores (Mean, Max, Total) in unaffected portions of bony skeleton.
Dr. Nauseef concluded this presentation of a quantitative assessment of PSMA imaging before and after 177Lu-PSMA-617 treatment with the following concluding statements:
- Sophisticated AI-based quantification analysis of PSMA expression on pre-and post-treatment 68Ga-PSMA11-PETs demonstrate associations with treatment efficacy (PSA response, OS), and associations between patient experience (adverse event) and PSMA expression in non-tumor tissues
- Expansion of this algorithm to a larger patient cohort may improve our ability to anticipate toxicity by body-wide PSMA detection and predict treatment response
Clinical trial information: NCT03042468.
Presented by: Jones T. Nauseef, MD, PhD, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
Co-Authors: Charlene Thomas, Michael Sun, A. Oliver Sartor, Sharon Singh, Mahelia Bissassar, Escarleth Fernandez, Angela Tan, Amie Patel, Juana Martinez Zuloaga, Muhammad Obaid Naiz, Dunya Imad, Shankar Vallabhajosula, Ana M. Molina, Cora N. Sternberg, David M. Nanus, Joseph Osborne, Neil Harrison Bander, Tim Perk, Scott T. Tagawa
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022