Are Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) and Prostate-Specific Membrane Antigen (PSMA) PET scans typically performed in the same setting for patients with suspected or confirmed prostate cancer?

FDG PET and PSMA PET Are Not Typically Performed in the Same Setting

FDG PET and PSMA PET are distinct imaging modalities used for different clinical scenarios in prostate cancer and are not routinely performed together in the same setting. PSMA PET has become the preferred molecular imaging modality for most prostate cancer evaluations, while FDG PET is reserved for specific aggressive disease phenotypes 1.

Standard Clinical Practice: PSMA PET as First-Line Molecular Imaging

• PSMA PET is the most sensitive imaging modality for detecting biochemically recurrent prostate cancer and should be performed instead of or after negative conventional imaging 1.
• PSMA-targeted PET (using 68Ga-PSMA-11 or 18F-PSMA tracers) is recommended for intermediate- to high-risk primary prostate cancer, biochemical recurrence after definitive therapy, and delineation of metastatic disease extent 2.
• For patients with biochemical recurrence following radical prostatectomy in whom salvage radiation is being considered, next generation molecular PET imaging (primarily PSMA) should be performed 1.

Limited Role of FDG PET in Routine Prostate Cancer Imaging

• FDG PET has limited utility in routine prostate cancer evaluation and is not recommended for standard staging or restaging 1.
• Data on the utility of FDG-PET/CT in patients with prostate cancer is limited, and its routine use is not recommended 1.
• FDG PET identified local or metastatic disease in only 31% of patients with biochemical recurrence after radical prostatectomy, demonstrating poor sensitivity compared to PSMA tracers 1.

Specific Clinical Scenarios Where Dual-Tracer Imaging May Be Considered

High-Grade and Aggressive Disease Phenotypes

• As advanced metastatic prostate cancer migrates to high Gleason grade, dedifferentiates, or transforms to aggressive variants (such as small cell type), tumor cells convert to higher glucose metabolism, making FDG useful in this subset of patients 1.
• A subset of prostate cancer may not produce PSA or express PSMA, particularly poorly differentiated or neuroendocrine prostate cancer; in these instances, 18F-fluciclovine-PET/CT or FDG-PET may be useful 1.
• Variant histology (ductal and neuroendocrine) commonly results in PSMA-negative but FDG-positive imaging 3, 4.

Sequential Rather Than Simultaneous Imaging

• When dual-tracer imaging is indicated, FDG PET is typically performed AFTER PSMA PET shows negative or limited uptake, not in the same setting 3.
• In high-risk early castration-resistant prostate cancer with negative conventional imaging, FDG after PSMA PET improved detection of metastases from 65% to 73% 3.
• Positive FDG PET was found in 17% of men with negative PSMA PET for post-prostatectomy biochemical recurrence 3.

Predictive Factors for FDG Utility

• Gleason score ≥8 and higher PSA levels predict FDG-avid metastases in biochemical recurrence and primary staging 3.
• PSMA-negative primary tumor occurs in 5-10% of cases, where FDG may provide complementary information 1.

Practical Imaging Algorithm

For most prostate cancer patients:

1. Perform PSMA PET as the first-line molecular imaging modality 1, 2
2. Reserve FDG PET only for specific scenarios:
   • Negative PSMA PET with high clinical suspicion for disease 3
   • Gleason score ≥8 with aggressive features 3
   • Known or suspected neuroendocrine differentiation or variant histology 1, 4
   • Castration-resistant disease with rising PSA despite negative PSMA imaging 3

Important Caveats

• The two scans require different radiopharmaceuticals, separate injections, and distinct imaging protocols, making same-day acquisition logistically challenging and clinically unnecessary in most cases 2.
• PSMA overexpression is present in 90-95% of prostate cancers and increases with higher grade tumors and castrate resistance, making it the preferred single imaging modality 5.
• The cost and radiation exposure of performing both scans routinely would not be justified given the limited additional benefit in most patients 3.