(UroToday.com) The 2022 GU ASCO Annual meeting included a prostate cancer session featuring work from Dr. Masatoshi Hotta and colleagues presented results of an international multicenter retrospective study predicting the outcome of metastatic castration resistant prostate cancer (mCRPC) after Lu-177 PSMA therapy using semi-quantitative and visual criteria in baseline PSMA PET. High PSMA expression is associated with better response to PSMA radioligand therapy. Patients with higher tumor uptake compared to the liver would allow enrolment of more patients, but some of these patients will have poor response. Patients with higher tumor uptake compared to the parotid gland (a higher threshold than the liver) can select patients who will benefit more from PSMA radioligand therapy. As such, the aim of this study was to assess the use of the baseline PSMA PET tumor to parotid gland uptake ratio (PSG score) as a reference to determine eligibility for Lu-177 PSMA radioligand therapy by using semi-quantitative and standardized visual criteria.
This was a retrospective cohort study using a multicenter dataset of 270 men with mCRPC treated with Lu-177 PSMA.1 For quantitative analysis, semi-automatic segmentation software (qPSMA) divided men into three groups according to the SUVmean ratio of whole-body-tumor to parotid glands (qPSG score):
- High > 1.5
- Intermediate 0.5 - 1.5
- Low < 0.5
For visual analysis, ten nuclear medicine physicians with (n = 5) and without (n = 5) clinical experience in Lu-177 PSMA radioligand therapy (> 50 cases) read each baseline PSMA PET 3D maximum intensity projection images, and classified the patients into three groups (vPSG):
- High: most (> 80%) of the lesions show higher uptake than parotid glands
- Intermediate: neither “low” nor “high”
- Low: most (> 80%) of the lesions show lower uptake than parotid glands
In case of inter-reader disagreement, a majority vote was used. Outcome measures included PSA-progression free-survival (PSA-PFS), overall survival, and PSA decline of ≥50% (PSA50). Fisher’s exact test and Kaplan–Meier analysis with the log-rank test was performed for PSA50 and survival analysis, respectively.
There were 237 men analyzed after excluding 33 men with more than half of the parotid glands out of the PET scan field-of-view. The number of patients in the high, intermediate, and low groups were 106/237 (44.7%), 96 (40.5%), and 35 (14.8%) for visual criteria, and 56 (23.6%), 163 (68.8%), and 18 (7.6%) for quantitative analysis, respectively. The inter- and intra-readers reproducibility of the visual scoring showed substantial (Fleiss’ weighted Kappa: 0.68) and almost perfect (Cohen's weighted Kappa (mean): 0.83) agreement, respectively. The median PSA-PFS was 6.7, 3.8, and 1.9 months (p < 0.001); and 7.2, 4.0, and 1.9 months (p < 0.001) in the high, intermediate, and low expression groups by visual and quantitative criteria, respectively. The qPSG and vPSG scores successfully stratified the patients based on PSA response as highlighted in the Kaplan Meier curves for PSA-PFS:
The PSA50 was 63.2%, 33.3%, and 17.1% (p < 0.001), and 69.6%, 38.7%, and 16.7% (p < 0.001) in the high, intermediate, and low expression groups by visual and quantitative criteria, respectively. Overall survival was longer in the high PSMA expression group than in the intermediate + low (i.e., non-high) group by visual (14.3 vs.11.0 months, HR 1.3, 95% CI 1.0-1.8; p = 0.039) and quantitative criteria (15.0 vs. 11.7 months, HR 1.5, 95% CI 1.1-2.2; p = 0.014):
Dr. Hotta concluded his presentation assessing the tumor-to-parotid uptake using a visual or semi-quantitative measure as a prognostic biomarker for response in men with mCRPC treated with Lu-177 PSMA radioligand therapy with the following take-home messages:
- The PSG score is a valuable predictive biomarker for response to Lu-177 PSMA
- The vPSG score yielded substantial reproducibility and comparable predictive value to the qPSG score
- Although prospective validation is warranted, the proposed criteria may assist individual decision-making and clinical trial design
Presented by: Masatoshi Hotta, MD, University of California Los Angeles, Los Angeles, CA, Ahmanson Translational Theranostics Division, University of California, Los Angeles, CA
Co-Authors: Andrei Gafita, Vishnu Murthy, Matthias R. Benz, Ida Sonni, Irene Burger, Matthias Eiber, Louise Emmett, Andrea Farolfi, Wolfgang Peter Fendler, Michael S Hofman, Thomas A Hope, Clemens Kratochwil, Johannes Czernin, Jeremie Calais
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022