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Prognostic biomarkers in men with metastatic castration-resistant prostate cancer receiving [177Lu]-PSMA-617

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Abstract

Purpose

We analysed quantitative biomarkers derived from both baseline whole-body imaging and blood serum to identify prognostic markers in patients treated within the lutetium-177 prostate-specific membrane antigen (LuPSMA) phase 2 trial.

Methods

PET image analysis was carried out using whole-body segmentation quantifying molecular tumour volume (SUV > 3 threshold for PSMA, SUV > liver+2sd for fluorodeoxyglucose (FDG) including SUVmax and SUVmean. For baseline bone scans, EXINI bone scan index (BSI) was used to calculate the percentage of involved bone. Baseline alkaline phosphatase (ALP), lactate dehydrogenase (LDH), prostate specific antigen (PSA) and PSA doubling time were also used in this analysis. We used univariate cox regression analysis and log-rank comparison with optimised cut-offs to find suitable biomarkers prognostic of overall survival from time of enrolment.

Results

This analysis identified FDG-positive tumour volume (FDGvol; HR 2.6; 95% CI, 1.4–4.8), mean intensity of PSMA-avid tumour uptake (PSMAmean; HR 0.89; 95% CI, 0.8–0.98), bone scan index (BSI; HR 2.3; 95% CI, 1.2–4.4), ALP (HR 1.1; 95% CI, 1–1.2) and LDH (HR 1.2; 95% CI, 1–1.5) as biomarkers prognostic of overall survival.

Conclusions

In addition to established biomarkers, both FDG and PSMA PET/CT parameters have prognostic significance for survival in men undergoing LuPSMA therapy.

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References

  1. Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [(177)Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19:825–33. https://doi.org/10.1016/S1470-2045(18)30198-0.

    Article  CAS  PubMed  Google Scholar 

  2. Violet J, Sandhu S, Iravani A, Ferdinandus J, Thang SP, Kong G, et al. Long term follow-up and outcomes of re-treatment in an expanded 50 patient single-center phase II prospective trial of Lutetium-177 ((177)Lu) PSMA-617 theranostics in metastatic castrate-resistant prostate cancer. J Nucl Med. 2019. https://doi.org/10.2967/jnumed.119.236414.

  3. Rahbar K, Ahmadzadehfar H, Kratochwil C, Haberkorn U, Schafers M, Essler M, et al. German multicenter study investigating 177Lu-PSMA-617 radioligand therapy in advanced prostate cancer patients. J Nucl Med. 2016. https://doi.org/10.2967/jnumed.116.183194.

  4. Heck MM, Tauber R, Schwaiger S, Retz M, D'Alessandria C, Maurer T, et al. Treatment outcome, toxicity, and predictive factors for radioligand therapy with (177)Lu-PSMA-I&T in metastatic castration-resistant prostate cancer. Eur Urol. 2019;75:920–6. https://doi.org/10.1016/j.eururo.2018.11.016.

    Article  CAS  PubMed  Google Scholar 

  5. Thang SP, Violet J, Sandhu S, Iravani A, Akhurst T, Kong G, et al. Poor outcomes for patients with metastatic castration-resistant prostate cancer with low prostate-specific membrane antigen (PSMA) expression deemed ineligible for (177)Lu-labelled PSMA radioligand therapy. Eur Urol Oncol. 2019;2:670–6. https://doi.org/10.1016/j.euo.2018.11.007.

    Article  PubMed  Google Scholar 

  6. Kessel K, Seifert R, Schafers M, Weckesser M, Schlack K, Boegemann M, et al. Second line chemotherapy and visceral metastases are associated with poor survival in patients with mCRPC receiving (177)Lu-PSMA-617. Theranostics. 2019;9:4841–8. https://doi.org/10.7150/thno.35759.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Violet J, Jackson P, Ferdinandus J, Sandhu S, Akhurst T, Iravani A, et al. Dosimetry of (177)Lu-PSMA-617 in metastatic castration-resistant prostate cancer: correlations between pretherapeutic imaging and whole-body tumor dosimetry with treatment outcomes. J Nucl Med. 2019;60:517–23. https://doi.org/10.2967/jnumed.118.219352.

    Article  CAS  PubMed  Google Scholar 

  8. Fizazi K, Massard C, Smith M, Rader M, Brown J, Milecki P, et al. Bone-related parameters are the main prognostic factors for overall survival in men with bone metastases from castration-resistant prostate cancer. Eur Urol. 2015;68:42–50. https://doi.org/10.1016/j.eururo.2014.10.001.

    Article  PubMed  Google Scholar 

  9. Armstrong AJ, Anand A, Edenbrandt L, Bondesson E, Bjartell A, Widmark A, et al. Phase 3 assessment of the automated bone scan index as a prognostic imaging biomarker of overall survival in men with metastatic castration-resistant prostate cancer: a secondary analysis of a randomized clinical trial. JAMA Oncol. 2018;4:944–51. https://doi.org/10.1001/jamaoncol.2018.1093.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Jadvar H, Desai B, Ji L, Conti PS, Dorff TB, Groshen SG, et al. Baseline 18F-FDG PET/CT parameters as imaging biomarkers of overall survival in castrate-resistant metastatic prostate cancer. J Nucl Med. 2013;54:1195–201. https://doi.org/10.2967/jnumed.112.114116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hofman MS, Emmett L, Violet J, Zhang A Y, Lawrence NJ, Stockler M, et al. TheraP: a randomized phase 2 trial of (177) Lu-PSMA-617 theranostic treatment vs cabazitaxel in progressive metastatic castration-resistant prostate cancer (Clinical Trial Protocol ANZUP 1603). BJU Int. 2019;124(Suppl 1):5–13. https://doi.org/10.1111/bju.14876.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

EXINI quantitative bone analysis was kindly performed by Dr. Lars Edenbrandt. MH is supported by a Clinical Fellowship from the Peter MacCallum Foundation. For the clinical study, Lutetium-177 was kindly supplied by the Australian Nuclear Science and Technology Organisation ANSTO, Sydney, Australia) and PSMA-617 from Advanced Biochemical Compounds (ABX, Radeberg, Germany) and Endocyte (a Novartis company). MH additionally acknowledges grant support from Movember Australia, Prostate Cancer Foundation (PCF), the Prostate Cancer Foundation of Australia (PCFA), US Department of Defence and the Victorian Cancer Agency (VCA).

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Correspondence to Michael S. Hofman.

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Conflict of interest

MH is the chair of the ANZUP TheraP Study which receives research support from Prostate Cancer Foundation of Australia (PCFA) and Endocyte (a Novartis company). Unrelated to this work, he has received honorarium and travel support from Janssen, Ipsen and Sanofi Genzyme. RJH is supported by a National Health and Medical Research Foundation Practitioner Fellowship and receives research support from the Neuroendocrine Tumor Research Foundation (NETRF), Clarity Pharmaceuticals and Ipsen. He holds stock in Telix Pharmaceuticals. SS reports a consulting or advisory role for Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Astra Zeneca, Janssen and Roche; and research funding from research support from the Movember Australia, Prostate Cancer Foundation (PCF), the Victoria Cancer Agency (VCA), Endocyte, Astra Zeneca, Amgen, Bristol-Myers Squibb and Merck Sharp & Dohme.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Peter Mac ethics committee (approval date: 26 August 2015) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This trial is registered with the Australian New Zealand Clinical Trials Registry, number 12615000912583. This article does not contain any studies with animals performed by any of the authors. The study was investigator-initiated and sponsored by the Peter MacCallum Cancer Centre, Melbourne, Australia. All patients signed written informed consent prior to participation in the study. The authors are responsible for the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review and approval of the manuscript. MSH had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Data sharing

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

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Ferdinandus, J., Violet, J., Sandhu, S. et al. Prognostic biomarkers in men with metastatic castration-resistant prostate cancer receiving [177Lu]-PSMA-617. Eur J Nucl Med Mol Imaging 47, 2322–2327 (2020). https://doi.org/10.1007/s00259-020-04723-z

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