Can PSMA PET Parameters Help Predict Toxicity and Outcomes in Patients Treated for mCRPC?

For patients with metastatic castration-resistant prostate cancer (mCRPC), quantification of parameters from prostate-specific membrane antigen (PSMA) positron emission tomography (PET) led to some intriguing findings for predicting hematologic toxicity in those treated with (¹⁷⁷Lu)Lu-PSMA-617 in newly published research.

For the retrospective study, recently published in the Journal of Nuclear Medicine, researchers employed artificial intelligence (AI) software (TRAQinform IQ, AIQ Global) to help quantify baseline PSMA PET parameters, including prostate tumor volume, mean standardized uptake value (SUVmean), maximum SUV (SUVmax) and total lesion PSMA (TLP) in 61 patients with mCRPC who received (¹⁷⁷Lu)Lu-PSMA-617.

The researchers found that patients with a higher bone TLP had a 31 percent higher risk of earlier onset of severe toxicity. However, in a recent interview with Diagnostic Imaging, study co-author Jeremie Calais, M.D., Ph.D., emphasized caution with the findings given the small cohort and expressed a preference for assessing the SUVmean and prostate tumor volume separately as opposed to the multiplication of SUVmean and prostate tumor volume with TLP.

“This (TLP) parameter is a nice way to combine them both, but at the end, you don't understand, really, biologically what it represents,” maintained Dr. Calais, the director of the clinical research program for nuclear medicine and theranostics at the University of California, Los Angeles (UCLA).

However, multivariable analysis also revealed a significant association between pronounced PSMA expression in bone metastasis and delayed onset of grade 3 and 4 toxicities in patients treated with (¹⁷⁷Lu)Lu-PSMA-617.

“Maybe the hypothesis is that it will bring more radiopharmaceutical therapy because there is more target expression so we would kill maybe more tumor metastasis lesions, enabling potentially more regrowing of the healthy bone marrow after … tumor cell killing, therefore maybe preserving or improving a little bit the hematologic impact and toxicity,” suggested Dr. Calais, an associate professor at UCLA.

(Editor’s note: For related content, see “Can an Integrated Approach with PSMA PET/CT and Prostate MRI Enhance Detection of Extraprostatic Extension?,” “Should PSMA PET/CT Supplant MRI for Staging of Patients with High-Risk PCa?” and “Top Five Prostate Cancer Imaging Content in 2025.”)

For more insights from Dr. Calais, watch the video below.