Development of a Visually Calculated SUV_mean(HIT Score) on Screening PSMA PET/CT to Predict Treatment Response to¹⁷⁷Lu-PSMA Therapy: Comparison with Quantitative SUV_meanand Patient Outcomes

Abstract

¹⁷⁷Lu-PSMA therapy is an effective treatment in patients with metastatic castration-resistant prostate cancer. SUV_mean is a valuable screening biomarker to assess the suitability for ¹⁷⁷Lu-PSMA therapy but requires quantitative software. This study aims to develop a simple, clinically applicable prostate-specific membrane antigen PET/CT score that encompasses the elements of SUV_mean without requiring additional quantification. <b>Methods:</b> Datasets from ethics-approved trials of patients with metastatic castration-resistant prostate cancer after androgen receptor signaling inhibition and taxane chemotherapy (or unfit for taxane), who were treated with ¹⁷⁷Lu-PSMA-617 and ¹⁷⁷Lu-PSMA I&T with a pretreatment screening with ⁶⁸Ga-PSMA-11 PET/CT, and clinical outcome data, including a prostate-specific antigen (PSA) 50% response rate (PSA50), PSA progression-free survival (PSA-PFS), and overall survival (OS), were included. The screening ⁶⁸Ga-PSMA-11 PET/CT of all participants was analyzed both semiquantitatively and visually. Semiquantitative analysis was used to derive the SUV_mean Visual analysis of the ⁶⁸Ga-PSMA-11 PET/CT images involved a binary visual heterogeneity assessment (homogeneous or heterogeneous), allocating a tumor SUV_max range (<15, 15-29, 30-49, 50-79, or ≥80). A 4-category score incorporating both heterogeneity and intensity of tumors (HIT) was then developed as a combination of heterogeneity and intensity (SUV_max range). The SUV_max was less than 15 for score 1, 15-79 with heterogeneous intensity for score 2, 15-79 with homogeneous intensity for score 3, and 80 or greater for score 4. This score was evaluated according to clinical outcomes (PSA50, PSA-PFS, and OS) and compared with SUV_mean <b>Results:</b> Data from 139 participants were analyzed. In total, 75 (54%) patients achieved a PSA50 with a median PSA-PFS of 5.5 mo (95% CI, 4.1-6.0 mo) and an OS of 13.5 mo (95% CI, 11.1-17.9 mo). SUV_mean was associated with PSA50 and survival outcomes when analyzed as a continuous variable or as quartiles. The PSA50 for HIT scores 1-4 was 0%, 39%, 65%, and 76%, respectively. The HIT score was strongly related to PSA-PFS and OS (log-rank test, <i>P</i> < 0.001 and <i>P</i> = 0.002). The median PSA-PFS for HIT scores 1-4 was 1.0, 4.1, 6.0, and 8.5, respectively, and the median OS was 7.6, 12.0, 18.5, and 16.9 mo, respectively. Cohen κ between readers for the HIT score was 0.71. <b>Conclusion:</b> A prostate-specific membrane antigen PET/CT score incorporating HIT derived from tools on a standard PET workstation is comparable with quantitative SUV_mean as a prognostic tool following ¹⁷⁷Lu-PSMA therapy.