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PEER-TO-PEER CLINICAL CONVERSATIONS
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SPECT Versus PET: Optimizing Response Biomarkers
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Lisa Bodei, MD, PhD
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| Lisa Bodei reviews PSMA response biomarkers for lutetium-177 PSMA therapy, including data from TheraP and VISION showing that baseline SUVmean, whole-body tumor volume, and absorbed dose may help predict treatment response beyond PSA changes alone. She also discusses how PSMA PET and SPECT may provide complementary information for monitoring response and understanding resistance.
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PROSTest mRNA Assay Evaluated for Predicting Response to 177Lu-PSMA in mCRPC
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Mark Kidd, PhD
Mark Kidd describes PROSTest, an mRNA blood assay designed to measure tumor biology genes, and reviews its prospective multicenter evaluation in men with mCRPC undergoing lutetium-177 PSMA therapy.
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PSMA-Targeted Radiopharmaceuticals: Patient Selection, Safety, and Response Monitoring
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Dustin Boothe, MD, Neal D. Shore, MD, FACS, Tanya Dorff, MD, and Phillip Koo, MD
Tanya Dorff, Neal Shore, Dustin Boothe, and Phillip Koo discuss multidisciplinary considerations for PSMA-targeted radiopharmaceuticals in advanced prostate cancer, including imaging-based patient selection, biomarker assessment, safety and tolerability, treatment goals, and how response monitoring may inform ongoing management.
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| Does Early 177Lu-PSMA-617 SPECT/CT Improve Prognostic Assessment Beyond Baseline PSMA PET in mCRPC?
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| Yalda Nikanpour, MD
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| In a retrospective study of 50 mCRPC patients, early change in SPECT-derived tumor volume between cycles 1 and 2 of 177Lu-PSMA-617 added significant prognostic value beyond baseline PSMA PET tumor volume. The addition of this early volumetric response improved prediction of overall survival, PSA progression-free survival, and radiographic progression-free survival in nested Cox models. These findings suggest that early post-therapy SPECT/CT may provide additional information for response assessment and risk stratification during PSMA radioligand therapy.
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| Predicting Early PSA Response to 177Lu-PSMA Therapy Using Baseline PET Imaging Biomarkers and Cycle 1 Dosimetry
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| Molly Roseland, MD
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| This study found that higher baseline PSMA PET SUVmean and greater whole-body tumor absorbed dose in cycle 1 of 177Lu-PSMA were associated with better PSA responses, including at 3 months after completing therapy. Patients who responded had higher mean SUVmean and absorbed dose, supporting previously reported associations between absorbed dose, SUVmean thresholds, and meaningful response. These results suggest that routine assessment of whole-body SUVmean on baseline PSMA PET, potentially supplemented by early dosimetry, may help predict prognosis and inform treatment planning.
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| Associations Between Quantitative Baseline 68Ga-PSMA-11 PET Parameters and 177Lu-PSMA-617 Efficacy in the PSMAfore Study
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| Ken Herrmann, MD
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| In PSMAfore, higher baseline SUVmean was linked to better outcomes with 177Lu-PSMA-617, and larger PSMA tumor volume signaled worse outcomes in both arms. 177Lu-PSMA-617 improved progression-free survival across SUVmean subgroups, with greater benefit observed among patients with higher SUVmean; patients with soft-tissue-only disease had the most favorable outcomes.
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| Baseline PSMA PET Tumor Volume Predicts Overall Survival with 177Lu-PSMA-I&T in Individual mCRPC Patients: A Single-Center Real-World Study
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| Kwan Kit Wu, MBChB (CUHK), FHKCR, FHKAM
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| Kwan Kit Wu discusses this single-center study of 55 mCRPC patients in which baseline PSMA PET whole-body tumor volume was a strong, independent predictor of long-term overall survival after 177Lu-PSMA-I&T, with a clear split around 196 mL and tighter thresholds of <165 mL for 2-year and <116 mL for 3-year survival.
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| How to Better Personalize Treatment with 177Lu-PSMA-617
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| Louise Emmett, MD, MBChB, FRACP, FAANMS
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| Louise Emmett outlined approaches to personalizing 177Lu-PSMA-617, including the use of PSMA PET criteria to help identify patients more or less likely to respond, and by incorporating quantitative biomarkers like SUVmean, ctDNA, and whole-body PSMA tumor volume to better predict outcomes. She discussed combining ARPIs with PSMA therapy, using adaptive dosing and early imaging/PSA response to guide treatment holidays and re-treatment, and pursuing rational combination strategies with immune agents, DNA damage response inhibitors, and alpha-emitters.
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