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&amp;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 (&lt;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> &lt; 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.