Advancing Patient Care Through Precision PSMA PET/CT Imaging

The emergence of prostate-specific membrane antigen (PSMA)-directed PET/CT is transforming staging and treatment decisions for prostate cancer patients. Growing data support its impact on patient outcomes and standard clinical care pathways, and clinical guidelines have been updated to recommend PSMA PET/CT imaging for patients with suspected metastases, biochemical recurrence (BCR) based on elevated prostate-specific antigen (PSA) levels, and nonmetastatic castration-resistant prostate cancer with elevated PSA; it also may be used to monitor patients with advanced prostate cancer for progression and to determine eligibility for PSMA-directed radioligand therapy.^1-3

Recent studies have evaluated the impact of PSMA PET/CT imaging on staging of prostate cancer and on clinical management decisions. Ahead is a brief summary of studies that have evaluated the use of 2 of the FDA-approved PSMA tracers currently available: gallium 68 (⁶⁸Ga) PSMA-11 (also known as Ga 68 gozetotide), fluorine 18 (¹⁸F)- DCFPyL (also known as piflufolastat F-18).

PSMA PET-CT Imaging Impact on Treatment Decisions

18F-DCFPyL

Results of the phase 3 CONDOR trial (NCT03739684) of patients with BCR prostate cancer showed that 63.9% of patients had a change in the intended management plan for their prostate cancer.⁴ These findings were based on physician responses to management questionnaires given before and after PET/CT imaging using fluorine F 18 piflufostat (¹⁸F-DCFPyL) PSMA. A secondary analysis was completed to evaluate the clinical utility of ¹⁸F-DCFPyL PSMA PET/CT in a subset of 69 men with very low or low prostate-specific antigen (PSA) levels (< 0.5 ng/mL).⁵

Prior to PET imaging, the patients received a single dose injection of ¹⁸F-DCFPyL. Patients also completed questionnaires about the intended management of their prostate cancer before and after imaging. Treatment recommendations that changed from those indicated on questionnaires given before imaging were counted as changes in the intended management plan.⁵

This analysis demonstrated that use of ¹⁸F-DCFPyL PSMA PET/CT imaging altered planned management in more than 39% of patients with PSA levels below 0.5 ng/mL. In 74.1% of patients with a reported change in management, the initial intended treatment was intensified as a result of the imaging. Notably, negative and positive imaging results impacted management decisions; this could prevent under- or overtreatment for individual patients.

⁶⁸Ga–PSMA-11

The impact of gallium 68 gozetotide (⁶⁸Ga–PSMA-11) on treatment management decisions for patients with prostate cancer was evaluated in a prospective study of 197 patients.⁶ The results demonstrated that use of ⁶⁸Ga–PSMA-11 PET/CT imaging resulted in changes to the staging of prostate cancer in 69% of patients—the disease was upstaged in 38% of these patients, downstaged in 30% of patients, and not changed in the remaining 32% of patients.

Researchers used pre- and postimaging questionnaires, electronic health record reviews, or phone calls to patients to assess whether management decisions were altered. For 57% of patients, management decisions were impacted. The most frequent change was a shift from systemic to focal treatment for 16% of these patients.⁶

Patients with BCR or presurgical staging were excluded from this study; therefore, the researchers concluded that these findings confirmed the benefit of PSMA PET/CT imaging on treatment decisions across all clinical scenarios.⁶

Additionally, a study by Müller et al assessed the impact of ⁶⁸Ga–PSMA-11 PET/CT imaging on management and outcomes of 223 patients with recurrent prostate cancer.⁷ PSMA PET/CT results detected recurrence in 74% of patients, including 50% of patients with low PSA levels (< 0.5 ng/mL); they led to a management change in 60% of cases. After PSMA PET/CT imaging, the use of metastasis-targeted radiotherapy increased, whereas systemic therapy decreased. Also, 45% of patients treated with PSMA PET–directed focal therapy for positive lesions experienced a complete response after 6 months. The results confirmed the high detection rate for recurrence related to use of PSMA PET and demonstrated its ability to guide personalized treatment through precise lesion localization.⁷

Impact of Patient Outcomes

Whether modifying treatment plans based on PSMA PET/CT imaging analysis impacts patient outcomes in the long term has not been determined. Until survival data mature, the results of these trials affirm the meaningful impact that PSMA molecular imaging has on patient care.

References

1. Fendler WP, Eiber M, Beheshti M, et al. PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0. Eur J Nucl Med Mol Imaging. 2023;50(5):1466-1486. doi:10.1007/s00259-022-06089-w

2. NCCN. Clinical Practice Guidelines in Oncology. Prostate cancer, version 4.2023. Accessed October 3, 2023. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf

3. Lowrance W, Dreicer R, Jarrard DF, et al. Updates to advanced prostate cancer: AUA/SUO guideline (2023). J Urol. 2023;209(6):1082-1090. doi:10.1097/JU.0000000000003452

4. Morris MJ, Rowe SP, Gorin MA, et al; CONDOR Study Group. 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;27(13):3674-3682. doi:10.1158/1078-0432.CCR-20-4573

5. Pouliot F, Gorin MA, Rowe SP, et al. Changes in planned disease management after piflufolastat F18 PET/CT in men with biochemically recurrent prostate cancer and low PSA levels: a secondary analysis of results from the CONDOR study. J Clin Oncol. 2023;41(suppl 6):61. doi:10.1200/JCO.2023.41.6_suppl.61

6. Sonni I, Eiber M, Fendler WP, et al. Impact of ⁶⁸Ga-PSMA-11 PET/CT on staging and management of prostate cancer patients in various clinical settings: a prospective single-center study. J Nucl Med. 2020;61(8):1153-1160. doi:10.2967/jnumed.119.237602

7. Müller J, Ferraro DA, Muehlematter UJ, et al. Clinical impact of ⁶⁸Ga-PSMA-11 PET on patient management and outcome, including all patients referred for an increase in PSA level during the first year after its clinical introduction. Eur J Nucl Med Mol Imaging. 2019;46(4):889-900. doi:10.1007/s00259-018-4203-0