SNMMI 2024: Prognostic Value of Post-Therapy SPECT/CT Imaging in Patients Undergoing 177Lu-PSMA-617 Radioligand Therapy: Results from 3 Clinical Trials

(UroToday.com) The 2024 Society of Nuclear Medicine & Molecular Imaging (SNMMI) annual meeting featured a session on prostate cancer, and a presentation by Dr. Raghava Karri discussing the prognostic value of post-therapy SPECT/CT imaging in patients undergoing ¹⁷⁷Lu-PSMA-617 (Lu-PSMA) radioligand therapy. Despite established efficacy of Lu-PSMA, as evidenced by the TheraP¹ and VISION² trials, there remains a notable gap in understanding the utility of post-therapy imaging. At the 2024 SNMMI annual meeting, Dr. Karri and colleagues reviewed changes on post-therapy SPECT/CT as a prognostic biomarker compared to PSA and conventional prognostic parameters in three clinical trials.

This was a retrospective analysis of post-therapy SPECT/CT images of patients receiving at least two cycles of Lu-PSMA therapy from three clinical trials. Patients from a Peter MacCallum phase 2 (n = 46), PRINCE (n = 25), and LuPARP (n = 14) studies were included. Molecular tumor volume was contoured on the post-therapy images with an SUV cut-off of 3. Total lesion activity was derived as a product of molecular tumor volume and SUV_mean, and PET parameters were correlated with PSA change at cycle 2 (Pearson’s correlation coefficient). Prognostic value of new lesions (detected visually) on SPECT/CT at cycle 2, change in molecular tumor volume, total lesion activity, and SUVmax at cycle 2 on overall survival was assessed using Cox proportional hazard model, adjusting by age, Gleason score and change in PSA.

There were 85 patients with metastatic castration-resistant prostate cancer analyzed with a median age of 71 (IQR 67-75) years. There was moderate correlation between change in PSA from cycle 1 to cycle 2 and molecular tumor volume (r = 0.56 [95% CI 0.40 - 0.69] p < 0.001) or total lesion activity (r = 0.55 [0.39 - 0.69] p < 0.001 for total lesion activity). Reduction in total lesion activity (HR 0.98, 95% CI 0.97, 1.00; p = 0.016) and molecular tumor volume (HR 0.98, 95% CI 0.96, 1.00; p = 0.009; per 10% increased for both) were associated with overall survival on univariable analysis but not in multivariate analysis when adjusting for clinical factors. Changes in SUV_max and SUV_mean were not associated with overall survival (HR 0.98, 95% CI 0.93 - 1.03; p = 0.38 and HR 0.98, 95% CI 0.86 - 1.11; p = 0.71, respectively). There were 18 of 85 (21.2%) patients that had new lesions on cycle 2 SPECT/CT, and this was prognostic for overall survival in univariate and multivariate analysis (HR 2.38, 95% CI 1.36 - 4.18, p = 0.002; HR 2.85, 95% CI: 1.36 - 5.98, p = 0.01):
Notably, 7/85 (8.2%) of patients with PSA reduction had new lesions developing on the post-therapy SPECT/CT images.

Dr. Karri concluded his presentation discussing the prognostic value of post-therapy SPECT/CT imaging in patients undergoing LuPSMA radioligand therapy with the following take-home messages:

Volumetric parameters on SPECT/CT (molecular tumor volume, total lesion activity) showed prognostic value for overall survival in univariate analysis
New lesions on SPECT/CT were strongly prognostic in uni- and multivariate analysis
This suggests that SPECT/CT findings are clinically relevant as they may be visible even in patients with declining PSA

Presented by: Raghava K. Karri, MD, Nuclear Medicine Physician, Peter MacCallum Cancer Centre, Melbourne, Australia

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, WWellStarMCG Health, @zklaassen_md on Twitter during the 2024 Society of Nuclear Medicine & Molecular Imaging (SNMMI) Annual Meeting, Toronto, Ontario, Canada, Sat, June 8 – Tues, June 11, 2024

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