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Influence of localization of PSMA-positive oligo-metastases on efficacy of metastasis-directed external-beam radiotherapy—a multicenter retrospective study

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Abstract

Purpose

Approximately 40–70% of biochemically persistent or recurrent prostate cancer (PCa) patients after radical prostatectomy (RPE) are oligo-metastatic in 68gallium-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET). Those lesions are frequently located outside the prostate bed, and therefore not cured by the current standards of care like external-beam radiotherapy (EBRT) of the prostatic fossa. This retrospective study analyzes the influence of oligo-metastases’ site on outcome after metastasis-directed radiotherapy (MDR).

Methods

Retrospectively, 359 patients with PET-positive PCa recurrences after RPE were analyzed. Biochemical recurrence-free survival (BRFS) (prostate-specific antigen (PSA) < post-radiotherapy nadir + 0.2 ng/mL) was assessed using Kaplan-Meier survival and Cox regression analysis.

Results

All patients were initially clinically without distant metastases (cM0). Seventy-five patients had local recurrence within the prostatic fossa, 32 patients had pelvic nodal plus local recurrence, 117 patients had pelvic nodal recurrence, 51 patients had paraaortic lymph node metastases with/without locoregional recurrence, and 84 patients had bone or visceral metastases with/without locoregional recurrence. Median PSA before MDR was 1.2 ng/mL (range, 0.04–47.5). Additive androgen deprivation therapy (ADT) was given in 35% (125/359) of patients. Median PSA nadir after MDR was 0.23 ng/mL (range, < 0.03–18.30). After a median follow-up of 16 months (1–57), 239/351 (68%) patients had no biochemical recurrence. Patients with distant lymph node and/or distant metastases, the so-called oligo-body cohort, had an overall in-field control of 90/98 (91%) but at the same time, an ex-field progress of 44/96 (46%). In comparison, an ex-field progress was detected in 28/154 (18%) patients with local and/or pelvic nodal recurrence (oligo-pelvis group). Compared with the oligo-pelvis group, there was a significantly lower BRFS in oligo-body patients at the last follow-up.

Conclusion

Overall, BRFS was dependent on patterns of metastatic disease. Thus, MDR of PSMA PET-positive oligo-metastases can be offered considering that about one-third of the patients progressed within a median follow-up of 16 months.

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Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital LMU Munich, Marchioninistr. 15, 81377, Munich, Germany

    N.-S. Schmidt-Hegemann & C. Belka

  2. Department of Radiation Oncology, University Hospital Zürich, Zurich, Switzerland

    S.G.C. Kroeze & M. Guckenberger

  3. Department of Radiotherapy and Special Oncology, Medical School Hannover, Hannover, Germany

    C. Henkenberens & H. Christiansen

  4. Department of Radiation Oncology, Technical University of Munich, Munich, Germany

    M.M.E. Vogel & S.E. Combs

  5. Institute of Radiation Medicine (IRM), Department of Radiation Sciences, Helmholtz Zentrum München, Unterschleissheim, Munich, Germany

    M.M.E. Vogel & S.E. Combs

  6. Department of Radiation Oncology, University of Freiburg, Freiburg im Breisgau, Germany

    S. Kirste & A.L. Grosu

  7. Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany

    J. Becker & A.C. Müller

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

    I. A. Burger

  9. Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany

    T. Derlin

  10. Department of Nuclear Medicine, University Hospital LMU Munich, Munich, Germany

    P. Bartenstein

  11. Department of Nuclear Medicine, Technical University Munich, Munich, Germany

    M. Eiber

  12. Department of Nuclear Medicine, University of Freiburg, Freiburg im Breisgau, Germany

    M. Mix

  13. Department of Nuclear Medicine, University Hospital Tübingen, Tübingen, Germany

    Ch. la Fougère

  14. German Cancer Consortium (DKTK), Partner Site Tübingen, Tübingen, Germany

    Ch. la Fougère

  15. Cluster of Excellence iFIT (EXC 2180) “Image Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany

    Ch. la Fougère

  16. German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany

    A.L. Grosu

  17. German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany

    S.E. Combs & C. Belka

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  1. N.-S. Schmidt-Hegemann
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by N.-S. Schmidt-Hegemann, S.G.C. Kroeze, C. Henkenberens, M.M.E. Vogel, S. Kirste, and J. Becker. The first draft of the manuscript was written by N.-S. Schmidt-Hegemann, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to N.-S. Schmidt-Hegemann.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committees of the respective Medical Faculties (Business Administration System for Ethics Committees Number (BASEC-Nr. 2017–01499)) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

This retrospective multicenter study was undertaken in six university hospitals in Switzerland and Germany, was approved by the local Ethics Committee of the respective Medical Faculties (BASEC-Nr. 2017–01499), and the need for written informed consent was waived.

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Schmidt-Hegemann, NS., Kroeze, S., Henkenberens, C. et al. Influence of localization of PSMA-positive oligo-metastases on efficacy of metastasis-directed external-beam radiotherapy—a multicenter retrospective study. Eur J Nucl Med Mol Imaging 47, 1852–1863 (2020). https://doi.org/10.1007/s00259-020-04708-y

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