Imaging response assessment with post 177Lu-PSMA-617 therapy SPECT-CT in metastatic castrate resistant prostate cancer: Adding value with a technologist driven post-processing workflow

Introduction: 177Lu-PSMA-617 treatment has proven effective against metastatic castrate resistant prostate cancer. Gamma emissions of 177Lu allow serendipitous monitoring of treatment response using SPECT-CT; however, post therapy SPECT is likely less sensitive than PET in response assessment. We aim to clarify concordance of change in quantitative measures of tumor burden with treatment on post therapy SPECT vs. follow-up PET-CT.

Methods: Two Nuclear Medicine Technology Students (NMTS) utilized a MIM post-processing workflow to segment uptake above an absolute threshold (SUV max ≥ 4) on 68Ga PSMA PET and post 177Lu PSMA SPECT, then manually distinguished physiologic from lesion uptake. A board-certified radiologist proofed final contours. 10 consecutive cases having completed at least 5 cycles of 177Lu-PSMA-617 treatment with follow up PET within 7 days were processed. Concordance between PET and SPECT in percent change from pretreatment values for SUV max, total lesions SUV mean and volume, and total lesion uptake (TLU; mean x volume) was assessed using linear regression and Bland Altman (BA) analysis.

Results: Concordance between percent change on SPECT vs. PET for SUV max, mean, volume and TLU was generally moderate to high after 3 (r² = 0.53, 0.40, 0.66, 0.64) and 5 (r² = 0.36, 0.60, 0.43, 0.57) cycles (all p<0.05). Excluding 1 influential outlier, BA showed high agreement for complete and near-complete responses, with increasing uncertainty and bias toward underestimation of remaining tumor burden on SPECT with increasing residual disease on PET (Figure).

Conclusions: Concordance in change from baseline for PSMA PET vs. post 177Lu PSMA therapy SPECT was overall moderate at 3 and 5 month following initiation of treatment. We observed stronger concordance for total tumor burden measures such as total lesion mean SUV, volume and TLU compared to SUV max in the hottest lesion. Complete or near complete response on SPECT showed strong agreement, with diminishing agreement and underestimation of tumor burden on SPECT in patients with more residual disease on PET. We anticipate ongoing work to assess whether change in these quantitative parameters predicts progression free and overall survival and adverse effects as our cohort completes 177Lu PSMA for metastatic castrate resistant prostate cancer.

Quantitative segmentation of total tumor burden can be time consuming but showed better agreement for post-treatment change on SPECT and PET in our cohort. Collaboration between NMTS and radiologists in post processing helped make a quantitative approach more feasible.

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