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Heterogeneity of [68Ga]Ga-PSMA-11 PET/CT in metastatic castration-resistant prostate cancer: genomic characteristics and association with abiraterone response

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Abstract

Purpose

The aim of this study was to evaluate the impact of the spatial heterogeneity of prostate-specific membrane antigen (PSMA) uptake on circulating tumor DNA (ctDNA) characteristics and the response rate to new hormonal agent (NHA) treatment.

Methods

This retrospective study included 153 patients with metastatic castration-resistant prostate cancer (mCRPC) who underwent gallium-68 [68 Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) and ctDNA sequencing with a less than 2-week interval. SUVhetero was defined as the variance of SUVmean for each PSMA-positive lesion. SUVmax-mean was obtained by subtracting the SUVmax by the SUVmean. Patients receiving abiraterone treatment after [68 Ga]Ga-PSMA-11 PET/CT and ctDNA sequencing and with complete follow-up record were included into prostate-specific antigen (PSA) response rate analysis. PSA response was defined as a reduction of greater than 50% from baseline.

Results

The ctDNA detection rate was 65% (100/153). Higher SUVhetero value contributed to higher ctDNA% (Spearman’s rho = 0.278, p < 0.002). A total of 60 patients were included in PSA response rate analysis. The median follow-up was 19.3 (IQR 16.2–23.2) months. Compare to patients with higher SUVhetero value, patients with NA SUVhetero had a higher PSA response rate (52% vs. 90%, p = 0.036). A higher SUVmax-mean value was strongly correlated with higher SUVhetero (Spearman’s rho = 0.833, p < 0.0001). Patients with higher SUVmax-mean value also had a higher PSA response rate compared to patients with lower SUVmax-mean value (83.3% vs. 53.3%, p = 0.024). An external cohort confirmed baseline SUVmax-mean value was associated with enzalutamide treatment response rate. Patients with alterations in AR, DNA damage repair pathway, TP53, AR-associated pathway, cell cycle pathway, or WNT pathway had higher SUVmax-mean value compared to those without (p < 0.05).

Conclusion

Spatial heterogeneity of the PSMA uptake was associated with ctDNA characteristics and response rate to NHA treatment.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the patients who participated in the studies. And we thank Jianxin Ke, Xiang Pan, Zhishu Dong, and Xiangjiang Chen, who gave strong support to the present study.

Funding

National Natural Science Foundation of China (81972375, 82172621, 81902568, and 82203106), Shanghai Anti-Cancer Association Eyas Project (SACA-CY22A04), Shanghai Sailing Program (21YF1408100), Shanghai Medical Innovation Research Special Project (21Y11904300), Shanghai Shenkang Research Physician Innovation and Transformation Ability Training Project (SHDC2022CRD035), Clinical Research Plan of SHDC (SHDC2020CR2016B), and Beijing Xisike Clinical Oncology Research Foundation (Y-2019AZMS-0012 and Y-MSDZD2021-0230).

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Authors and Affiliations

  1. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China

    Jian Pan, Jinou Zhao, Xudong Ni, Yu Wei, Tingwei Zhang, Beihe Wang, Junlong Wu, Dingwei Ye & Yao Zhu

  2. Shanghai Genitourinary Cancer Institute, Shanghai, China

    Jian Pan, Jinou Zhao, Xudong Ni, Yu Wei, Tingwei Zhang, Beihe Wang, Junlong Wu, Dingwei Ye & Yao Zhu

  3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Jian Pan, Jinou Zhao, Xudong Ni, Bin Zhu, Xiaoxin Hu, Qifeng Wang, Yu Wei, Tingwei Zhang, Hualei Gan, Beihe Wang, Junlong Wu, Shaoli Song, Chang Liu, Dingwei Ye & Yao Zhu

  4. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China

    Bin Zhu, Shaoli Song & Chang Liu

  5. Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China

    Xiaoxin Hu

  6. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China

    Qifeng Wang & Hualei Gan

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  1. Jian Pan
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Jian Pan, Jinou Zhao, Bin Zhu, Xiaoxin Hu, Qifeng Wang, Yu Wei, Tingwei Zhang, Hualei Gan, Beihe Wang, Chang Liu, and Junlong Wu. The first draft of the manuscript was written by Jian Pan, Jinou Zhao, Shaoli Song, Dingwei Ye, and Yao Zhu. Xudong Ni revised the manuscript. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Beihe Wang, Junlong Wu, Shaoli Song, Chang Liu, Dingwei Ye or Yao Zhu.

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Ethics approval

The study involving human participants was in line with the principles of the ethics committee of Fudan University Shanghai Cancer Center and the Declaration of Helsinki in 1964. This study does not include animal research.

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The authors affirm that human research participants provided informed consent for publication of the images in Fig. 6.

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Informed consent was waived due to the retrospective nature of this study.

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The authors declare no competing interests.

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Jian Pan is the first author.

This article is part of the Topical Collection on Oncology—Genitourinary.

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Pan, J., Zhao, J., Ni, X. et al. Heterogeneity of [68Ga]Ga-PSMA-11 PET/CT in metastatic castration-resistant prostate cancer: genomic characteristics and association with abiraterone response. Eur J Nucl Med Mol Imaging 50, 1822–1832 (2023). https://doi.org/10.1007/s00259-023-06123-5

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