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Malignant lipogenesis defined by 11C-acetate PET/CT predicts prostate cancer-specific survival in patients with biochemical relapse after prostatectomy

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Abstract

Purpose

Malignant de novo lipogenesis is strongly linked to the aggressiveness of prostate cancer (PCa) under experimental conditions. 11C-Acetate PET/CT is a potential noninvasive biomarker of malignant lipogenesis in PCa, but its prognostic value is not known. The objective of this study was to analyse 11C-acetate PET/CT image metrics in relation to survival.

Methods

All patients undergoing 11C-acetate PET/CT in one university hospital from 2005 to 2011 due to PSA relapse after previous prostatectomy were retrospectively evaluated. Two groups of patients were compared: those who died from PCa and those who were censored. All previously reported findings of local recurrence, regional or distal lymph node metastases and bone metastases were counted and evaluated regarding 11C-acetate uptake intensity (SUVmax) and tumour volume. Total tumour volume and total lipogenic activity (TLA, summed SUVmax × TV) were calculated. Survival analysis in the entire study population was followed by Cox proportional hazards ratio (HR) analysis.

Results

A total of 121 patients were included, and 22 PCa-specific deaths were recorded. The mean PSA level at the time of PET was 2.69 ± 4.35 ng/mL. The median follow-up of the study population was 79 ± 28 months. PET identified at least one PCa lesion in 53 % of patients. Five-year PCa-specific survival after PET was 80 % and 100 % in patients with a positive and a negative PET scan, respectively (p < 0.001). Time-to-death was linearly correlated with highest SUVmax (r = −0.55, p = 0.01) and nonlinearly with TLA (r = −0.75, p < 0.001). Multivariate analysis showed statistical significance for number of bone metastases (HR 1.74, p = 0.01), tertile of TLA (HR 5.63, p = 0.029) and postoperative Gleason score (HR 1.84, p = 0.045).

Conclusion

Malignant 11C-acetate accumulation measured with PET/CT is a strong predictor of survival in the setting of PSA relapse after prostatectomy. The study provides further evidence for a quantitative relationship between malignant de novo lipogenesis and early death. 11C-Acetate PET/CT might be useful for identifying a high-risk population of relapsing patients in which therapies targeting malignant lipogenesis might be of particular benefit.

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Acknowledgments

The authors express sincere thanks to the Uppsala PET Centre staff for their dedicated efforts.

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Authors and Affiliations

  1. Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

    Naresh Regula & Jens Sörensen

  2. Section of Urology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

    Michael Häggman

  3. Section of Oncology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

    Silvia Johansson

  4. PET Center Research Department, no. 79, 5th floor, Akademiska Sjukhuset, 751 85, Uppsala, Sweden

    Jens Sörensen

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  1. Naresh Regula
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Corresponding author

Correspondence to Jens Sörensen.

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Funding

This work was supported by the Swedish Cancer Foundation (CAN 2014/827).

Conflicts of interest

None.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments. Ethical approval for this retrospective study was obtained from the Institutional ethical review board at the Department of Oncology (Dnr IRB 5/2015).

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The need for individual patient consent was waived.

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Regula, N., Häggman, M., Johansson, S. et al. Malignant lipogenesis defined by 11C-acetate PET/CT predicts prostate cancer-specific survival in patients with biochemical relapse after prostatectomy. Eur J Nucl Med Mol Imaging 43, 2131–2138 (2016). https://doi.org/10.1007/s00259-016-3449-7

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  • DOI: https://doi.org/10.1007/s00259-016-3449-7

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