SNMMI 2024: Development of a Visually Calculated SUVmean (HIT Score) on Screening PSMA PET/CT to Predict Treatment Response to 177Lu PSMA Therapy: Comparison to Quantitative SUVmean and Patient Outcomes

(UroToday.com) The 2024 Society of Nuclear Medicine & Molecular Imaging (SNMMI) annual meeting featured a session on prostate cancer, and a presentation by Dr. Mina Swiha discussing the development of a visually calculated SUVmean (HIT Score) on screening PSMA PET/CT to predict treatment response to 177Lu PSMA therapy. 177Lu-PSMA is an effective treatment in patients with metastatic castrate-resistant prostate cancer, and SUVmean is a valuable screening biomarker to assess suitability for 177Lu-PSMA therapy but requires quantitative software. This study aimed to develop a simple clinically applicable PSMA-PET score that encompasses the elements of SUVmean, without requiring additional quantification.

Datasets of patients from ethics approved trials with metastatic castrate-resistant prostate cancer post androgen receptor signaling inhibition and post taxane (or unfit for taxane), treated with 177Lu-PSMA (617 and I&T) with a prior screening 68Ga-PSMA-11 PET/CT, and clinical outcome data (50% PSA response rate (PSA50), PSA progression free survival and overall survival) were included.  

The screening PSMA-PET of participants were analyzed both semi-quantitatively and visually. Semi-quantitative analysis was used to derive SUVmean. Visual analysis was undertaken by three experienced nuclear medicine specialists blinded to clinical outcome and included evaluation of tumoral heterogeneity on rotating three-dimensional maximum-intensity-projection images adjusted to SUV window range (0-15). Heterogeneity was a binary score. If 80% or greater of all lesions not impacted by partial voluming (larger lesions) had similar intensity, this was classified as ‘homogeneous’. If more than 20% of larger lesions had variable intensity (inter or intra-lesional), this was classified as ‘heterogeneous’: 

image-0.jpg 

Secondly, readers measured SUVmax of the most intense lesion and allocated an SUVmax range (<15, 15-29, 30-49, 50-79, ≥80). A four-category score (HIT) was then developed as a combination of heterogeneity and intensity (SUVmax-range). Score 1 was all patients with an SUVmax < 15, Score 2 was patients defined as having heterogeneous disease visually with an SUVmax between 15-79, Score 3 was patients with visually homogeneous disease and an SUVmax between 15-79, and Score 4 included all patients with an SUVmax ≥ 80 independent of whether tumor was homogeneous or heterogeneous. This score was evaluated according to clinical outcomes (PSA50, PSA progression free survival and overall survival), and compared with SUVmean.

Between 2016 and 2022, data from 139 participants were analyzed and all patients received a median four doses 177Lu-PSMA 7.5 GBq. Overall, 75 (54%) patients achieved PSA50 with a median PSA progression free survival of 5.5 months (95% CI 4.1 – 6.0) and overall survival of 13.5 months (95% CI 11.1 – 17.9). The median semi-quantitatively derived SUVmean was 8.0 (IQR 6.6 – 9.9). Increasing SUVmean as a continuous variable demonstrated a strong relationship with a higher probability of PSA50 and lower hazard of PSA progression free survival and overall survival. When assessed as quartiles, SUVmean significantly predicted PSA progression free survival (p < 0.001) with borderline significance for overall survival (p = 0.051).

The distribution of HIT score among the sample was: Score 1 n = 5 (3.6%), Score 2 n = 54 (39%), Score 3 n = 63 (45%), and Score 4 n = 17 (12%). The following shows the HIT score (1-4) color-coded table incorporating SUVmax range (most intense lesion) and binary visual heterogeneity with patient numbers in each group:

image-1.jpg

The PSA50 for the HIT score 1-4 was 0%, 39%, 65%, and 76% respectively, and HIT score was strongly related to PSA progression free survival and overall survival (log-rank p < 0.001 and p = 0.002). Median PSA progression free survival for HIT score 1-4 was 1.0, 4.1, 6.0, and 8.5 and median overall survival 7.6, 12.0, 18.5, and 16.9 months, respectively. Inclusion of heterogeneity significantly improved prediction of SUVmean above that of SUVmax range (likelihood ratio test, p = 0.0041), hence both factors were required: 

image-2.jpg

Cox models with the HIT score had comparable predictive power as SUVmean quartiles for PSA progression free survival (Somers' D = 0.25 vs 0.27) and overall survival (0.15 vs 0.16) and exceeded those for SUVmax range quartiles (progression free survival 0.17, overall survival 0.12). Cohen’s Kappa between readers for the HIT score was 0.71 and percentage agreement was 82%.

Dr. Swiha concluded his presentation discussing the development of a visually calculated SUVmean (HIT Score) on screening PSMA PET/CT to predict treatment response to 177Lu PSMA therapy with the following take home messages:

  • A PSMA-PET score incorporating both heterogeneity and intensity of tumors (HIT) derived from tools available on a standard PET workstation, is comparable to quantitative SUVmean as a prognostic tool following 177Lu-PSMA therapy
  • Further studies are warranted to validate the clinical utility of the HIT score

Presented by: Mina Swiha, MD, PhD, St. Vincent Hospital, Sydney, Australia

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 Society of Nuclear Medicine & Molecular Imaging (SNMMI) Annual Meeting, Toronto, Ontario, Canada, Sat, June 8 – Tues, June 11, 2024.