SNMMI 2023: Extension of a 68Ga-PSMA PET-Based Nomogram for Outcome Prediction of 177Lu-PSMA Radioligand Therapy for the Use of 18F-rhPSMA -7.3

(UroToday.com) The 2023 SNMMI annual meeting included a prostate cancer session, featuring a presentation by Dr. Isabel Rauscher discussing the extension of a ⁶⁸Ga-PSMA PET-based nomogram for outcome prediction of ¹⁷⁷Lu-PSMA radioligand therapy for the use of ¹⁸F-rhPSMA -7.3.

Recently, ¹⁷⁷Lu-PSMA radioligand therapy has been approved by the FDA and EMA for patients with metastatic-castration resistant prostate cancer (mCRPC) based on the phase 3 VISION trial.¹ Given that a response to ¹⁷⁷Lu-PSMA radioligand therapy is not achieved by all patients, nomograms, including pre-therapeutic ⁶⁸Ga-PSMA-PET, were recently established to predict outcomes:²

PSA response

However, the increasing use of ¹⁸F-labelled PSMA-ligands requires adaptation of these methods. The aim of this retrospective analysis was to assess application of the ⁶⁸Ga-PSMA-PET-based recently published nomogram for use with ¹⁸F-rhPSMA- 7.3 (POSLUMA^®) prior to Lu-PSMA radioligand therapy in a large cohort of patients with mCRPC.

A total number of 174 patients (median age 74, interquartile range 68-80 years) were retrospectively included in this study. Parameters included the same as the ⁶⁸Ga-PSMA PET nomogram clinical variables (time since diagnosis, chemotherapy status, baseline hemoglobin)and imaging data now derived from¹⁸F-rhPSMA-7.3 PET (tumor SUVmean, >=20 metastatic lesions, presence of pelvic lymph node, bone and/or liver metastases). Pre-therapeutic outcome probabilities (PSA-progression-free survival and overall survival) for each patient were estimated according to the published ⁶⁸Ga-PSMA PET-based prediction models [2]. To assess the use of ¹⁸F-rhPSMA-7.3 in this nomogram, the observed and estimated outcome of each patient c-index were calculated for overall survival and progression-free survival. Finally, overall survival and progression-free survival were compared, stratifying patients in high- and low-risk groups based on the cut-off values determined by Gafita et al [2].

The estimated median progression-free survival and overall survival were 3.7 months (95% CI, 3.0-5.2) and 14.9 months (95%CI, 12.8-18.0), respectively. The observed progression-free survival and overall survival were 3.1 months (95%CI, 2.4-3.8) and 12.1 months (95%CI, 10.7-13.4), respectively:

outcome parameter table

For the overall survival model, this data reached a C-index of 0.70 (95% CI 0.66-0.75), which is comparable to the validation cohort of Gafita et al. with a C-index of 0.72 (95%CI 0.68-0.76):¹

The C-index for PSA-progression-free survival was 0.64 (95% CI 0.60-0.70) and substantially lower compared to a C-index of 0.71 (95% CI 0.65-0.78) in the validation cohort of Gafita et al:

Grouping patients in high- and low-risk showed a strong stratification in short and long term outcomes. Low-risk patients presented with a significantly longer overall survival than high-risk patients (16.5 months (95% CI 15.1-17.8) vs. 8.8 months (95% CI 7.7-9.9), respectively; p < 0.0001). Corresponding PSA-progression-free survival was also significantly longer in the high-risk vs. the low-risk group (5.4 months (95% CI 4.7-6.1) vs. 2.6 months (95% CI 1.9-3.2); p = 0.003).

Dr. Rauscher concluded her presentation discussing the extension of a ⁶⁸Ga-PSMA PET-based nomogram for outcome prediction of ¹⁷⁷Lu-PSMA radioligand therapy for the use of ¹⁸F-rhPSMA -7.3 with the following take home messages:

The use of data from ¹⁸F-rhPSMA 7.3-PET substituting ⁶⁸Ga-PSMA in a recently proposed PET-based prediction nomogram performs well for assessing outcome of ¹⁷⁷Lu-PSMA radioligand therapy outcome assessment with similar c-indices for overall survival in comparison to the literature
However, irrespective of the PSMA-ligand used, the predictive accuracy of the nomogram is suboptimal and should be used with caution the decision on treatment initiation should be based on different factors
Further improvement of the model is warranted as prediction models might be beneficial in patient selection

Presented by: Isabel Rauscher, MD, Technical University of Munich, Munich, Germany

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.

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