Skip to main content
SpringerLink
Log in

Use of androgen deprivation and salvage radiation therapy for patients with prostate cancer and biochemical recurrence after prostatectomy

Anwendung einer Androgendeprivation zusätzlich zur Salvage-Strahlentherapie bei Patienten mit Prostatakarzinom und biochemischem Rezidiv nach Prostatektomie

  • Original Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Aim

Overview on the use of androgen deprivation therapy (ADT) added to salvage radiation therapy (SRT) for prostate cancer patients with biochemical recurrence after prostatectomy.

Methods

The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published between January 2009 and May 2017, and assessed the validity of the information on outcome parameters including overall survival (OS) and treatment-related toxicity.

Results

Two randomized controlled trials and nine relevant retrospective analyses were identified. The RTOG 9601 trial showed an OS improvement for the combination of 2 years of bicalutamide and SRT compared to SRT alone after a median follow-up of 13 years. This improvement appeared to be restricted to those patients with a prostate specific antigen (PSA) level before SRT of ≥0.7 ng/mL. The GETUG AFU-16 trial showed that after a median follow-up of 5 years, the addition of 6 months of goserelin to SRT improved progression-free survival (PFS; based on biochemical recurrence) as compared to SRT alone. ADT in both trials was not associated with increased major late toxicities. Results of retrospective series were inconsistent with a suggestion that the addition of ADT improved biochemical PFS especially in patients with high-risk factors such as Gleason Score ≥8 and in the group with initially negative surgical margins.

Conclusions

ADT combined with SRT appears to improve OS in patients with a PSA level before SRT of ≥0.7 ng/mL. In patients without persistent PSA after prostatectomy and PSA levels of <0.7 ng/mL, ADT should not routinely be used, but may be considered in patients with additional risk factors such as Gleason Score ≥8 and negative surgical margins.

Zusammenfassung

Ziel

Die vorliegende Übersichtsarbeit beschreibt den Nutzen einer Androgendeprivation (ADT) in Kombination mit einer Salvage-Strahlentherapie (SRT) bei Patienten mit Prostatakarzinom und biochemischem Rezidiv nach radikaler Prostatektomie.

Methoden

Das Expertengremium der Deutschen Gesellschaft für Radioonkologie (DEGRO) für das Prostatakarzinom hat die verfügbare Literatur von Januar 2009 bis Mai 2017 zusammengefasst und die vorliegenden Daten bezüglich Gesamtüberleben (OS) und Behandlungsnebenwirkungen beurteilt.

Ergebnisse

Insgesamt konnten 2 randomisierte Studien und 9 relevante retrospektive Analysen identifiziert werden. Die RTOG-9601-Studie zeigte eine Verbesserung des OS für die Kombination aus 2 Jahren Bicalutamid und SRT verglichen mit alleiniger SRT nach einer medianen Nachbeobachtungszeit von 13 Jahren. Allerdings war diese Verbesserung nur bei Patienten mit einem PSA-Wert vor SRT von ≥0,7 ng/ml nachweisbar. Die GETUG-AFU-16-Studie zeigte nach einer medianen Nachbeobachtungszeit von 5 Jahren, dass die Gabe von 6 Monaten Goserelin zur SRT das progressionsfreie Überleben (PFS), basierend auf der biochemischen Kontrolle, signifikant verbesserte. Die ADT schien in beiden Studien nicht mit vermehrten schweren Spätnebenwirkungen einherzugehen. Die Resultate der retrospektiven Fallserien sind inkonsistent und legen nahe, dass die zusätzliche Gabe einer ADT die biochemische Kontrolle verbessert, insbesondere bei Patienten mit Risikofaktoren wie Gleason-Score ≥8 und negativem Resektionsrand.

Schlussfolgerung

Eine ADT kombiniert mit SRT verlängert das OS bei Patienten mit einem PSA-Wert vor SRT von ≥0,7 ng/ml. Bei Patienten ohne persistierendem PSA nach radikaler Prostatektomie und PSA-Werten vor SRT von <0,7 ng/ml sollte eine ADT nicht routinemäßig angewendet werden. Sie kann bei Risikofaktoren wie Gleason-Score ≥8 und negativem Resektionsrand eingesetzt werden.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Han M, Partin AW, Zahurak M et al (2003) Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol 169:517–523

    Article  PubMed  Google Scholar 

  2. Ward JF, Moul JW (2005) Rising prostate-specific antigen after primary prostate cancer therapy. Nat Clin Pract Urol 2:174–182

    Article  PubMed  Google Scholar 

  3. Wiegel T, Bartkowiak D, Bottke D et al (2015) Prostate-specific antigen persistence after radical prostatectomy as a predictive factor of clinical relapse-free survival and overall survival: 10-year data of the ARO 96-02 trial. Int J Radiat Oncol Biol Phys 91:288–294

    Article  PubMed  Google Scholar 

  4. Tendulkar RD, Agrawal S, Gao T et al (2016) Contemporary update of a multi-institutional predictive nomogram for salvage radiotherapy after radical prostatectomy. J Clin Oncol. https://doi.org/10.1200/JCO.2016.67.9647

    Article  PubMed  Google Scholar 

  5. Stish BJ, Pisansky TM, Harmsen WS et al (2016) Improved metastasis-free and survival outcomes with early salvage radiotherapy in men with detectable prostate-specific antigen after prostatectomy for prostate cancer. J Clin Oncol 34(32):3864. https://doi.org/10.1200/jco.2016.68.3425

    Article  PubMed  Google Scholar 

  6. Roach M 3rd (2007) Dose escalated external beam radiotherapy versus neoadjuvant androgen deprivation therapy and conventional dose external beam radiotherapy for clinically localized prostate cancer: do we need both? Strahlenther Onkol 183:26–28

    Article  PubMed  Google Scholar 

  7. Bolla M, Van Tienhoven G, Warde P et al (2010) External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol 11:1066–1073

    Article  PubMed  CAS  Google Scholar 

  8. Fosså SD, Wiklund F, Klepp O et al (2016) The scandinavian prostate cancer group-7 investigators. Ten- and 15-yr prostate cancer-specific mortality in patients with nonmetastatic locally advanced or aggressive intermediate prostate cancer, randomized to lifelong endocrine treatment alone or combined with radiotherapy: final results of the Scandinavian prostate cancer group-7. Eur Urol 70:684–691

    Article  PubMed  Google Scholar 

  9. Gandaglia G, Briganti A, Clarce N et al (2017) Adjuvant and salvage radiotherapy after radical prostatectomy in prostate cancer patients. Eur Urol 72(5):689. https://doi.org/10.1016/j.eururo.2017.01.039

    Article  PubMed  Google Scholar 

  10. Shipley WU, Seiferheld W, Lukka HR et al (2017) Radiation with or without antiandrogen therapy in recurrent prostate cancer. N Engl J Med 376:417–428

    Article  PubMed  PubMed Central  Google Scholar 

  11. Carrie C, Hasbini A, de Laroche G et al (2016) Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol 17(6):747–756

    Article  PubMed  CAS  Google Scholar 

  12. Trock BJ, Han M, Freedland SJ et al (2008) Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA 299:2760–2769

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Jang JW, Hwang WT, Guzzo TJ et al (2012) Upfront androgen deprivation therapy with salvage radiation may improve biochemical outcomes in prostate cancer patients with post-prostatectomy rising PSA. Int J Radiat Oncol Biol Phys 83:1493–1499

    Article  PubMed  CAS  Google Scholar 

  14. Goenka A, Magsanoc JM, Pei X et al (2012) Long-term outcomes after high-dose postprostatectomy salvage radiation treatment. Int J Radiat Oncol Biol Phys 84:112–118

    Article  PubMed  Google Scholar 

  15. Soto DE, Passarelli MN, Daignault S, Sandler HM (2012) Concurrent androgen deprivation therapy during salvage prostate radiotherapy improves treatment outcomes in high-risk patients. Int J Radiat Oncol Biol Phys 82:1227–1232

    Article  PubMed  Google Scholar 

  16. Parekh A, Chen MH, Graham P et al (2015) Role of androgen deprivation therapy in early salvage radiation among patients with prostate–specific antigen level of 0.5 or less. Clin Genitourin Cancer 13:e1–e6

    Article  PubMed  Google Scholar 

  17. Ervandian M, Høyer M, Petersen SE et al (2016) Salvage radiation therapy following radical prostatectomy. A national Danish study. Acta Oncol 55:598–603

    Article  PubMed  CAS  Google Scholar 

  18. Holliday EB, Kuban DA, Levy LB et al (2017) Select men benefit from androgen deprivation therapy delivered with salvage radiation therapy after prostatectomy. Prostate Cancer Prostatic Dis 20(4):389. https://doi.org/10.1038/pcan.2017.24

    Article  PubMed  CAS  Google Scholar 

  19. Afshar-Oromieh A, Holland-Letz T, Giesel FL et al (2017) Diagnostic performance of 68 Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging 44(8):1258–1268

    Article  PubMed  PubMed Central  Google Scholar 

  20. Henkenberens C, von Klot CA, Ross TL et al (2016) (68)Ga-PSMA ligand PET/CT-based radiotherapy in locally recurrent and recurrent oligometastatic prostate cancer: Early efficacy after primary therapy. Strahlenther Onkol 192:431–439 (Jul)

    Article  PubMed  Google Scholar 

  21. Hermann RM, Christiansen H (2016) Salvage-Radiotherapie mit oder ohne Kurzzeit-Antihormonbehandlung beim PSA-Rezidiv (Literatur kommentiert). Strahlenther Onkol 192:741–744

    Article  PubMed  CAS  Google Scholar 

  22. Fossati N, Karnes RJ, Cozzarini C et al (2016) Assessing the optimal timing for early salvage radiation therapy in patients with prostate-specific antigen rise after radical prostatectomy. Eur Urol 69:728–733

    Article  PubMed  Google Scholar 

  23. Ohri N, Dicker AP, Trabulsi EJ et al (2012) Can early implementation of salvage radiotherapy for prostate cancer improve the therapeutic ratio? A systematic review and regression meta-analysis with radiobiological modelling. Eur J Cancer 48:837–844

    Article  PubMed  Google Scholar 

  24. King CR (2016) The dose-response of salvage radiotherapy following radical prostatectomy: a systematic review and meta-analysis. Radiother Oncol 121:199–203

    Article  PubMed  Google Scholar 

  25. Ghadjar P, Hayoz S, Bernhard J et al (2015) Acute toxicity and quality of life after dose-intensified salvage radiation therapy for biochemically recurrent prostate cancer after prostatectomy: first results of the randomized trial SAKK 09/10. J Clin Oncol 33:4158–4166

    Article  PubMed  CAS  Google Scholar 

  26. Bartkowiak D, Thamm R, Bottke D et al (2017) Prostate-specific antigen after salvage radiotherapy for postprostatectomy biochemical recurrence predicts long-term outcome including overall survival. Acta Oncol 17:1–6. https://doi.org/10.1080/0284186X.2017.1364869

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Radiation Oncology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Pirus Ghadjar MD & Dirk Böhmer

  2. Inselspital, University of Bern, Bern, Switzerland

    Daniel M. Aebersold

  3. Klinikum Nürnberg Nord, Nürnberg, Germany

    Clemens Albrecht

  4. Universitätsklinikum Würzburg, Würzburg, Germany

    Michael Flentje

  5. Ludwig-Maximilians-Universität München, Munich, Germany

    Ute Ganswindt

  6. Xcare Gruppe, Radiologie, Nuklearmedizin und Strahlentherapie, Saarlouis, Germany

    Stefan Höcht

  7. Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Tobias Hölscher

  8. Landeskrankenhaus, Universitätsklinikum, Paracelsus Medizinischen Privatuniversität, Salzburg, Austria

    Felix Sedlmayer

  9. Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany

    Frederik Wenz

  10. Universitätsklinikum Tübingen, Tübingen, Germany

    Daniel Zips

  11. Universitätsklinikum Ulm, Ulm, Germany

    Thomas Wiegel

Authors
  1. Pirus Ghadjar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel M. Aebersold
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Clemens Albrecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dirk Böhmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Flentje
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ute Ganswindt
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stefan Höcht
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tobias Hölscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Felix Sedlmayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Frederik Wenz
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Daniel Zips
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Thomas Wiegel
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Prostate Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO) and the Working Party Radiation Oncology of the German Cancer Society (DKG-ARO)

Corresponding author

Correspondence to Pirus Ghadjar MD.

Ethics declarations

Conflict of interest

P. Ghadjar, D.M. Aebersold, C. Albrecht, D. Böhmer, M. Flentje, U. Ganswindt, S. Höcht,T. Hölscher, F. Sedlmayer, F. Wenz, D. Zips, and T. Wiegel declare that they have no competing interests.

Ethical standards

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghadjar, P., Aebersold, D.M., Albrecht, C. et al. Use of androgen deprivation and salvage radiation therapy for patients with prostate cancer and biochemical recurrence after prostatectomy. Strahlenther Onkol 194, 619–626 (2018). https://doi.org/10.1007/s00066-018-1269-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-018-1269-3

Keywords

Schlüsselwörter

Search

Navigation