Abstract

The majority of patients with prostate cancer who later develop lethal metastatic disease have high-risk localized disease at presentation, emphasizing the importance of effective treatment strategies at this stage. Multimodal treatment approaches that combine systemic and local therapies offer a promising strategy for improving the clinical outcomes of patients with high-risk localized prostate cancer. Combinations of neoadjuvant and adjuvant chemotherapy, hormonal therapy, or chemohormonal therapy are considered to be the standard of care in most solid tumours and should be investigated in the future for the treatment of prostate cancer to improve patient outcomes. However, although the combination of androgen deprivation therapy and radiotherapy is a standard of care in high-risk localized or locally advanced prostate cancer, the benefit of chemotherapy or chemohormonal therapy has yet to be demonstrated outside of the metastatic setting. Moreover, the benefit of neoadjuvant and/or adjuvant systemic therapies in combination with radical prostatectomy has not been proved. The development of next-generation hormonal agents, which have been approved for the treatment of castration-resistant prostate cancer, offers further therapeutic possibilities that are being assessed in early-phase clinical trials.

Key points

  • Patients with high-risk localized prostate cancer have a poor prognosis and require an appropriate treatment strategy that considers a multimodal approach and includes both local and systemic therapies.

  • No benefit has been proved for any neoadjuvant or adjuvant hormonal therapy in the case of radical prostatectomy.

  • No benefit has been proved for chemotherapy administered before or after radical prostatectomy.

  • Long-term androgen deprivation therapy in combination with radiotherapy was shown to markedly improve survival outcomes and should therefore be proposed for patients with high-risk localized prostate cancer.

  • Additional evidence of the benefit of chemohormonal therapy in combination with radiotherapy is required in the neoadjuvant and adjuvant settings.

  • Next-generation hormone therapies are still under investigation in the neoadjuvant or adjuvant settings.

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Kattans’ nomogram: https://www.mskcc.org/nomograms/prostate

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Acknowledgements

The authors thank the KPL medical team for help with the preparation of this manuscript. The authors acknowledge the institutional support from Janssen. The authors are fully responsible for the content of and editorial decisions for this manuscript.

Review criteria

An analytical review of the literature was conducted in September 2016 using the PubMed database, with no time limit, using the following keywords arranged in various combinations: “localized prostate cancer”, “non-metastatic castration-resistant prostate cancer”, “multimodal treatment”, “chemotherapy”, “prostatectomy”, “adjuvant”, “neoadjuvant”, “abiraterone acetate”, and “enzalutamide”. From this research, 239 articles were identified, restricted to full-text English-language, covering retrospective and prospective studies, as well as randomized controlled trials and meta-analyses on hormonal therapies and/or chemotherapy in the adjuvant or neoadjuvant setting. The abstracts of these articles were reviewed. Relevant articles with pathological (pathological complete response) or oncological (progression-free survival and overall survival) results were included in the analysis. Five abstracts from international congresses were also considered contributory and corresponding to the research carried out. Finally, 40 articles were selected and organized according to the local treatment performed, prostatectomy, or radiotherapy. Relevant references cited in the selected full-text articles were also added to the analysis. Thus, the final number of references was 62. Ongoing trials on hormonal and/or chemotherapy in the adjuvant or neoadjuvant setting were searched for on the clinicaltrials.gov website and are also presented.

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Affiliations

  1. Service de Chirurgie Oncologique 2, Institut Paoli-Calmettes, Marseille, France

    • Géraldine Pignot
  2. Medical Oncology Department, Centre Hospitalier Lyon-Sud, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), Centre d’Investigation de Thérapeutiques en Oncologie et Hématologie de Lyon (CITOHL), Pierre-Bénite, France

    • Denis Maillet
  3. Ramsay Générale de Santé, Hôpital Privé Clairval, Marseille, France

    • Emmanuel Gross
  4. Medical Oncology Department, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

    • Philippe Barthelemy
  5. Department of Urology, CHU Rangueil, Toulouse, France

    • Jean-Baptiste Beauval
  6. Medical Oncology Department, CHIC Quimper, Quimper, France

    • Friederike Constans-Schlurmann
  7. Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Paris, France

    • Yohann Loriot
  8. Department of Urology, Clinique St Jean du Languedoc, Toulouse, France

    • Guillaume Ploussard
  9. Institut Universitaire du Cancer, Toulouse, France

    • Guillaume Ploussard
  10. Department of Radiation Therapy, Institut Bergonié, Bordeaux, France

    • Paul Sargos
  11. Department of Urology, Hôpital Européen Georges-Pompidou (HEGP), Assistance Publique-Hôpitaux de Paris (APHP), Paris, France

    • Marc-Olivier Timsit
  12. Paris-Descartes University, Paris, France

    • Marc-Olivier Timsit
  13. Department of Urology, Rennes University Hospital, Rennes, France

    • Sébastien Vincendeau
  14. Department of Urology, CHU Pellegrin, Bordeaux, France

    • Gilles Pasticier
  15. Department of Oncology, Antoine-Lacassagne Center, Nice, France

    • Delphine Borchiellini

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Contributions

G. Pignot, D.M., E.G., and D.B. researched data for the article and made substantial contributions to discussion of the content. G. Pignot, D.M., and D.B. wrote the article. All authors reviewed and/or edited the manuscript before submission.

Competing interests

G. Pignot is a consultant for Sanofi and Janssen. D.M. is a consultant for Janssen. E.G. is a consultant for Janssen and Sanofi. J.-B.B. is a consultant for Astellas, Ferring, Ipsen, and Janssen. F.C.-S. is a consultant for Astellas, Janssen, and Sanofi. Y.L. is a consultant for Astellas, Janssen, Sanofi, MSD, Roche, and AstraZeneca and has received research funding from Sanofi. G. Ploussard is an advisory board member and a consultant for Astellas, Ferring, IPSEN, Janssen, and Pierre Fabre. P.S. is a consultant and expert for Astellas, AstraZeneca, Ferring, Ipsen, Janssen, Nanobiotix, Roche, Sanofi, and Takeda. M.-O.T. was an invited speaker in symposia organized by Janssen, Astellas, and Pfizer. S.V. is a consultant for Astellas, Janssen, and Sanofi. G. Pasticier is a consultant for Astellas, Janssen, and Sanofi. D.B. is a consultant and advisory board member for Janssen, Sanofi, and Ipsen.

Corresponding author

Correspondence to Géraldine Pignot.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/s41585-018-0017-x

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