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Equivocal bone lesions on PSMA PET/CT: systematic review and meta-analysis on their prevalence and malignancy rate

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Abstract

Purpose

Prostate-specific membrane antigen (PSMA) PET/CT has an established reliable diagnostic performance for detecting metastases in prostate cancer. However, there are increasing instances of scans demonstrating equivocal bone lesions, with non-specific uptake and without a definite benign or malignant CT correlate. To date, the prevalence, malignancy rate, and relationship with radioligand type ([18F] PSMA-1007 vs. others ([68Ga]Ga-PSMA-11 and [18F] DCFPyL) for these equivocal lesions have not been extensively established.

Methods

A systematic review and meta-analysis was conducted on equivocal bone lesions. Pubmed and EMBASE were searched up to December 11, 2023. Quality of the studies was evaluated using QUADAS-2. The following proportions were pooled using random-effects model: (1) prevalence of equivocal bone lesions (i.e., number of patients with one or more equivocal bone lesions/number of patients with PSMA PET/CT) and (2) their malignancy rates (i.e., number of metastases/number of equivocal bone lesions). Subgroup analyses based on radioligand type, clinical setting, and definition of equivocal bone lesion were performed.

Results

Twenty-five studies (4484 patients) were included. Pooled prevalence of equivocal bone lesions was 20% (95%CI, 12–31%). [18F]PSMA-1007 was associated with a greater prevalence of equivocal lesions compared with other radioligands: 36% (95%CI 26–48%) vs. 8% (95%CI, 4–14%), respectively, p < 0.01. Pooled malignancy rate of equivocal bone lesions was 14% (95%CI, 7–25%). [18F]PSMA-1007 was associated with a lower malignancy rate compared to other radioligands: 8% (95%CI, 3–19%) vs. 29% (95%CI, 17–44%), respectively, p = 0.01. There were no signficant difference in prevalence or malignancy rate between subgroups stratified to clinical setting or definition of equivocal bone lesions (p = 0.32–0.60).

Conclusions

Equivocal bone lesions are often encountered on PSMA PET/CT but exihibit a low malignancy rate. Compared to other radioligands, [18F]PSMA-1007 requires special attention as it is associated with a higher frequency and lower rate of metastasis.

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Data availability

No datasets were generated or analysed during the current study.

Abbreviations

BVC:

best value comparator

MRI:

magnetic resonance imaging

PET/CT:

positron emission tomography/computed tomography

PSA:

prostate-specific antigen

PSMA:

Prostate-specific membrane antigen

PSMA-RADS:

PSMA Reporting and Data System

QUADAS-2:

Quality Assessment of Diagnostic Accuracy Studies-2

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Funding

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Authors and Affiliations

  1. Department of Radiology, NYU Langone Health, 660 1st Avenue, New York, NY, 10016, USA

    Sungmin Woo, Daniel Freedman, Anton S. Becker, Doris Leithner, Marius E. Mayerhoefer, Kent P. Friedman & Hebert A. Vargas

  2. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Yuki Arita

  3. Department of Nuclear Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea

    Sangwon Han

  4. Department of Nuclear Medicine, University Hospital Zürich, University of Zürich, Zürich, Switzerland

    Irene A. Burger

  5. Department of Nuclear Medicine, Kantonsspital Baden, Baden, Switzerland

    Irene A. Burger

  6. Department of Urology, NYU Langone Health, New York, NY, USA

    Samir S. Taneja

  7. Department of Medicine, Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, USA

    David R. Wise

  8. Department of Radiation Oncology, NYU Grossman School of Medicine, New York, NY, USA

    Michael J. Zelefsky

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Contributions

Study conceptualization: SW, HAV. Data acquisition: SW, DF, HAV. Data analysis: SW. Data interpretation: SW, ASB, DL, MEM, KPF, YA, SH, IAB, SST, DRW, MJZ, HAV. Drafting of manuscript: SW. Critical revision of manuscript: SW, ASB, DL, MEM, KPF, YA, SH, IAB, SST, DRW, MJZ, HAV. Supervision: HAV.

Corresponding author

Correspondence to Sungmin Woo.

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Ethical approval

This study did not involve individual human participant data as it was a systematic review and meta-analysis using only study-level summary data provided openly in the literature. Nevertheless, it was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki, its subsequent amendments, or comparable ethical standards.

Informed consent

This study did not involve individual human participant data as it was a systematic review and meta-analysis using only study-level summary data provided openly in the literature. As such, the need for informed consent was not applicable.

Competing interests

MEM received honoraria for lectures from Siemens, GE, and BM but unrelated to the current work. KPF is a co-investigator on “Optimizing timing of rhPSMA-7.3 (18F), for assessing site(s) of recurrent disease following radical prostatectomy” (PI Herbert Lepor) but does not receive any salary support and was unrelated to the current work. IAB has received research support from GE Healthcare and Bayer, speaker honorarium from GE-Healthcare, Baer, Astellas, Janssen and Novartis, and institutionally compensated advisory role for Novartis, Merck & Cie and Ratio Radiotherapeutics but unrelated to the current work. DRW has received consulting fees from Leap Therapeutics, Foundation Medicine, Pfizer, Janssen, Sanofi, Lilly, Labcorp, Myovant, Bayer, AstraZeneca, Accutar and has received travel funding from Pfizer and Bayer but unrelated to the current work. The other authors have nothing to disclose.

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Woo, S., Freedman, D., Becker, A.S. et al. Equivocal bone lesions on PSMA PET/CT: systematic review and meta-analysis on their prevalence and malignancy rate. Clin Transl Imaging (2024). https://doi.org/10.1007/s40336-024-00631-6

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