ASCO 2021: PSMA-Targeted Imaging with 18F-DCFPyL-PET/CT in Patients with Biochemically Recurrent Prostate Cancer: A Phase 3 Study (CONDOR)—A Subanalysis of Correct Localization Rate and Positive Predictive Value by Standard of Truth

(UroToday.com) PSMA-targeted PET/CT is superior to conventional imaging modalities to localize biochemically recurrent prostate cancer after local therapy, particularly in patients with low PSA (< 2 ng/mL) values. However, few studies have reported PSMA-targeted PET/CT accuracy compared to a pre-specified rigorous standard of truth including histopathology, correlative imaging, or treatment response in this population. The previously published CONDOR study focused on patients with biochemically recurrent disease, with a rising PSA after definitive therapy and negative or equivocal standard of care imaging (e.g., CT/MRI, bone scintigraphy, or F-18 fluciclovine)¹. In this study, PyL-PET/CT correctly localized lesions in 84.8-87.0% of cases among three readers (lower bound of 95% CI: 77.8%-80.4%) against the composite standard of truth. At the 2021 American Society of Clinical Oncology annual meeting, Dr. Frederic Pouliot and colleagues presented a subanalysis of correct localization rate and positive predictive value of PSMA-targeted ¹⁸F-DCFPyLPET/ CT for each of the pre-defined standard of truth criteria for the CONDOR prospective phase 3 study.

The study design for CONDOR is as follows:

For this study, a single 9 mCi (333 MBq) ± 20% dose of ¹⁸F-DCFPyL was injected, followed by PET/CT 1-2 hours later. Patients with positive ¹⁸F-DCFPyL-PET/CT scans based on local interpretation were scheduled for follow-up within 60 days to verify suspected lesion(s) using a composite standard of truth. The primary endpoint was the correct localization rate defined as positive predictive value with the requirement of anatomic lesion co-localization between ¹⁸F-DCFPyL-PET/CT and the standard of truth. The standard of truth consisted of, in descending priority:

Histopathology
Subsequent correlative imaging findings determined by two central readers
Post-radiation PSA response.

There were 208 men (with a median PSA of 0.8 ng/mL) that underwent ¹⁸F-DCFPyL-PET/CT and the study achieved its primary endpoint: correct localization rate was between 84.8% to 87.0% (lower bound of 95% CI: 77.8%-80.4%) among the three ¹⁸F-DCFPyL-PET/CT readers, against the composite standard of truth. The performance of ¹⁸F-DCFPyL-PET/CT by correct localization rate (≥1 lesion co-localized) and positive predictive value (≥1 lesion confirmed) was maintained through all 3 standards of truth categories:

Histopathology (n = 31): 78.6-82.8% and 92.9-93.3% for correct localization rate and positive predictive value, respectively
Correlative imaging (n = 100): 86.1-88.6% and 87.0-89.5% for correct localization rate and positive predictive value, respectively
PSA response (n = 1): 100% for both correct localization rate and positive predictive value

Further analyses of the correlative imaging results showed correct localization rate remained high across the different modalities used ¹⁸F-fluciclovine-PET/CT (N = 71): (86.8-90.9%); MRI (N = 23): (80.0-86.7%); and CT (n = 6): (80.0-100%).

Dr. Pouliot concluded this updated subanalysis of the CONDOR study with the following take-home/concluding messages:

The CONDOR study met the novel FDA recommended primary endpoint of correct localization rate, as the lower limit of the 95% CI greatly exceeded 20% by all 3 readers
PSMA-targeted ¹⁸F-DCFPyL-PET/CT detected and localized metastatic lesions with high correct localization rate and positive predictive value regardless of which criterion defined correct localization rate that was used
Novel standard of truth criteria based on correlative imaging shows similar performance when compared to histopathological standard of truth. Therefore, it can be used to determine correct localization rate and positive predictive value in future studies where biopsy is not possible

Clinical trial information: NCT03739684

Presented By: Frederic Pouliot, MD, Ph.D., FRCSC, Cancer Research Center, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec City, Canada

Written By: Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021

References:

Morris MJ, Rowe SP, Gorin MA, et al. Diagnostic Performance of ¹⁸F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase III, Multicenter Study. Clin Cancer Res. 2021 Feb 23 [Epub ahead of print].

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