SNMMI 2023: Post-Hoc Analysis of the LIGHTHOUSE and SPOTLIGHT Studies to Assess the Impact of Urinary Activity on Interpretation of 18F-rhPSMA-7.3 PET/CT

(UroToday.com) The 2023 SNMMI annual meeting included a prostate cancer session, featuring a presentation by Dr. Phillip Kuo discussing a post-hoc analysis of the LIGHTHOUSE and SPOTLIGHT studies to assess the impact of urinary activity on interpretation of ¹⁸F-rhPSMA-7.3 PET/CT. Radiohybrid (rh) ¹⁸F-rhPSMA-7.3 is a novel high affinity PSMA-targeting PET radiopharmaceutical currently under investigation as a diagnostic imaging tool for patients with prostate cancer:

Early clinical data showed that ¹⁸F-rhPSMA-7.3 has lower average urinary excretion compared to other renally-cleared PSMA-PET agents and thus has potential to improve image evaluation in the prostate and peri-ureteric regions.¹ The diagnostic performance of ¹⁸F-rhPSMA-7.3 has recently been investigated in two phase 3 studies: LIGHTHOUSE (NCT04186819) and SPOTLIGHT (NCT04186845). At the SNMMI 2023 annual meeting, Dr. Kuo and colleagues report results of a post-hoc analysis of all ¹⁸F-rhPSMA-7.3 scans acquired within these trials, to further assess the urinary tract activity of ¹⁸F-rhPSMA-7.3 and the influence on disease assessment.

Men with either treatment-naïve, newly diagnosed, unfavorable intermediate to very high-risk prostate cancer or with recurrent prostate cancer were enrolled in LIGHTHOUSE and SPOTLIGHT, respectively. All patients underwent PET/CT 50–70 min after IV administration of 8 mCi (296 MBq) ± 20% ¹⁸F-rhPSMA-7.3. For the present analysis, 718 ¹⁸F-rhPSMA-7.3 scans (352 from LIGHTHOUSE and 366 from SPOTLIGHT) were re-evaluated by a single reader with 25 years’ nuclear medicine experience who had completed ¹⁸F-rhPSMA-7.3 reader training:

Quantitative assessments (SUV_max and SUV_mean) of bladder activity were performed by placing a circular region of interest (ROI) over the maximum diameter of the activity in the bladder in the transverse plane: 

For qualitative assessments, the impact of any urinary excretion on the ability to assess the prostate/bed and pelvic/retroperitoneal lymph nodes, was evaluated using a 3-point scale:

• 0: no/minimally visible urinary activity
• 1: urinary activity visible but distinction between urine and disease possible
• 2: assessment inhibited by urinary activity

For ureteric activity (qualitative analysis), the presence or absence of a stasis of urine in keeping with ureteric activity was assessed. This was visualized on the MIP at a viewing window level of 0-10: 

For the halo artifact (qualitative assessment), the presence or absence of a gross photopenic region around the bladder extending significantly beyond the bladder and overlying the other structures of the pelvis was assessed in the transverse slices: 

Among the 718 eligible scans, 712 (348 newly diagnosed prostate cancer and 364 recurrent prostate cancer) were evaluable for bladder activity with the reasons for exclusion being cystectomy (n=2), renal failure (n=2), or presence of a urinary catheter(n=2). The median SUV_max in the bladder was 17.1 (IQR, 9.2–28.3) and median SUV_mean was 12.5 (IQR, 7.0–19.3):

As follows is the median bladder SUV_max and SUV_mean with reference to the published literature for renally-cleared PSMA PET agents: 

Qualitative data showed that for 87% (616/712) of patients, it was possible to distinguish between urinary activity and disease uptake. In the minority of patients (13%, 96/712) where urinary activity did affect the assessment (rated 2), the median bladder SUV_mean was found to be higher (19.7 vs 4.0 or 13.1 for those rated 0 or 1, respectively). Ureteric activity as defined by the presence of urine stasis was absent in 56% of patients by majority read. Finally, halo artifacts inhibiting assessment around the bladder were rare, occurring in only 0.3% of scans by majority read.

Dr. Kuo concluded his presentation discussing a post-hoc analysis of the LIGHTHOUSE and SPOTLIGHT studies to assess the impact of urinary activity on interpretation of ¹⁸F-rhPSMA-7.3 PET/CT with the following take home messages:

• Data from this post-hoc analysis of ¹⁸F-rhPSMA-7.3 scans from two prospective phase 3 trials show that the urinary activity of ¹⁸F-rhPSMA-7.3 is relatively low and does not influence disease assessment for the vast majority of patients
• Halo artifacts potentially inhibiting assessment occurred very rarely in this analysis
• Moreover, while this study was not designed as a head-to-head comparison, the median bladder SUVs compare favorably with values reported in the literature for other renally excreted PSMA-PET ligands
• The qualitative findings are being further investigated in a multi-reader analysis

Presented by: Phillip Kuo, MD, PhD, FACR, University of Arizona, Tucson, AZ

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, Chicago, IL, Sat, June 24 – Tues, June 27, 2023.

References:

1. Tolvanen T, Kalliokoski K, Malaspina S, et al. Safety, Biodistribution, and Radiation Dosimetry of ¹⁸F-rhPSMA-7.3 in Healthy Adult Volunteers. J Nucl Med. 2021;6(5):679-684.