ASCO 2022: PSMA PET Tumor-to-Salivary Glands Ratio (PSG Score) to Predict Response to Lu-177 PSMA Radioligand Therapy: An International Multicenter Retrospective Study

(UroToday.com) Despite the promise of PSA50 responses in about half of the patients treated on the phase III VISION study of 177Lu-PSMA, it cannot be overlooked that the balance of patients garnered little to no benefit from this emerging agent. One possible explanation for non-uniform response rates could arise from insufficiently specific patient selection. The authors of this study proposed that use of the parotid gland, an organ with typically higher PSMA expression on PSMA PET (as compared to liver) could serve as a better reference organ for more selective patient stratification.


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To test this hypothesis they developed a PSMA PET tumor-to-salivary gland ratio, named the PSG score, and evaluated its association with patient outcome. The international multicenter retrospective data of Gafita et al1 were evaluated, including 270 patients with mCRPC who were treated with 177Lu-PSMA. For each patient a baseline quantitative PSG score (qPSG) was calculated by dividing SUVmean of the whole-body tumor volume by the SUVmean of the parotid glands. These scores were then divided into three groups: high (qPSG>1.5), intermediate (0.5-1.5), and low (<0.5). Secondly, the predictive value and reproducibility of visual PSG scores (vPSG) by independent evaluation by 10 nuclear medicine physicians were measured. For this, each physician surveyed baseline PSMA PET 3D maximum intensity projection (MIP) images and classified the into three groups.

These included those with >80% of lesions with greater uptake than parotid (high), >80% of lesions with uptake less than parotid (low), and those in between (intermediate). When discordance was observed, a simple majority vote was used. Outcome measures were PSA-progression free-survival (PSA-PFS), overall survival (OS), and PSA response of ≥50% (PSA50).

After the exclusion of 33 patients for whom parotid glands were not captured in the field of the scans, the remaining 237 patients were analyzed. Most patients were Intermediate for qPSG, with the distribution as follows: High (n=56, 23.6%), Intermediate (n=163, 68.8%), and Low (n=18, 7.6%). The most common vPSG score category was High, as follows: High (n=106, 44.7%), Intermediate (n=96, 40.5%), and Low (n=35, 14.8%). The inter- and intra-readers reproducibility of the vPSG score showed substantial (Fleiss’ weighted Kappa: 0.68) and almost perfect (Cohen's weighted Kappa (mean): 0.83) agreement, respectively.

The median PSA-PFS of High, Intermediate, and Low groups were 7.2, 4.0, and 1.9 months (p < 0.001) for qPSG scores and 6.7, 3.8, and 1.9 months (p < 0.001) for vPSG scores, each respectively. Higher rates of PSA50 were observed in the High qPSG and vPSG groups, followed by Intermediate, and Low groups (qPSG: 69.6% vs 38.7% vs 16.7%; vPSG: 63.2% vs 33.3% vs 16.1%). The median OS was longer in the High group as compared to the remaining patients (the union of Intermediate and Low scores) for both qPSG and vPSG (qPSG: 15.0 vs. 11.7 months, p = 0.013; vPSG: 14.3 vs.11.0 months, p = 0.038).

PSA-PFS
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Overall Survival
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The authors conclude the use of the parotid gland as reference in determining SUV cutoffs for positive/negative PSMA PET/CT scans is a valid predictive imaging marker which corresponds to treatment response and outcomes following exposure to 177Lu-PSMA. As PSMA PET imaging and therapies gain additional presence in treatment of prostate cancer, continual refinement of patient selection and response measures, such as these, will require iteration and validation.

Presented by: Masatoshi Hotta, MD, University of California Los Angeles, Los Angeles, CA

Written by: Jones Nauseef, MD, PhD, Assistant Professor of Medicine within the Division of Hematology and Medical Oncology, Sandra and Edward Meyer Cancer Center, and Englander Institute for Precision Medicine Weill Cornell Medicine and Assistant Attending physician at NewYork-Presbyterian Hospital. @DrJonesNauseef on Twitter during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022. 

References:

  1. Gafita A, Calais J, Grogan TR, Hadaschik B, Wang H, Weber M, Sandhu S, Kratochwil C, Esfandiari R, Tauber R, Zeldin A, Rathke H, Armstrong WR, Robertson A, Thin P, D'Alessandria C, Rettig MB, Delpassand ES, Haberkorn U, Elashoff D, Herrmann K, Czernin J, Hofman MS, Fendler WP, Eiber M. Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study. Lancet Oncol. 2021 Aug;22(8):1115-1125. doi: 10.1016/S1470-2045(21)00274-6. Epub 2021 Jul 8. PMID: 34246328.
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