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The Efficacy and Safety of Metastasis-directed Therapy in Patients with Prostate Cancer: A Systematic Review and Meta-analysis of Prospective Studies - Beyond the Abstract

Metastasis-directed therapy (MDT) in the context of metastatic prostate cancer (mPCa) attracts significant scientific and practical interest. Its potential applications range from delaying androgen deprivation therapy (ADT) toxicity in metachronous mPCa, to treatment intensification in the context of multi-drug systemic treatments, and even strategies aimed at the total eradication of synchronous mPCa by combining MDT with local and systemic therapies.

However, understanding the emerging evidence is particularly challenging due to the interweaving concepts published across a multitude of smaller trials. Given that clinical application has outpaced the availability of high-quality data, there was an urgent need to synthesize the available evidence to address this knowledge gap. Therefore, we decided to provide a modern summary and meta-analysis of MDT trials in the treatment of mPCa.

We identified and summarized 22 prospective studies encompassing 1137 patients. Our analysis revealed encouraging results: a 2-year progression-free survival rate of approximately 46%, and 2-year rates for local control and overall survival at 97%. In studies where MDT was used to delay hormone therapy, 2-year ADT-free survival was 55%. Notably, the treatment exhibited an exceptionally low toxicity profile, with minimal grade 2 and ≥3 adverse events. However, while there is convincing evidence that MDT can delay ADT in selected metachronous mPCa patients, data is still insufficient to prove that MDT improves survival. Therefore, randomized trials powered for survival in the context of treatment intensification are eagerly awaited."

Written by:  Marcin Miszczyk,1 Pawel Rajwa,2 Takafumi Yanagisawa,3 Zuzanna Nowicka,4 Sung Ryul Shim,5 Ekaterina Laukhtina,6 Tatsushi Kawada,7 Markus von Deimling,8 Benjamin Pradere,9 Juan Gómez Rivas,10 Giorgio Gandaglia,11 Roderick C. N. van den Bergh,12 Gregor Goldner,13 Stephane Supiot,14 Thomas Zilli,15 Quoc-Dien Trinh,16 Paul L. Nguyen,17 Alberto Briganti,11 Piet Ost,18 Guillaume Ploussard,19 Shahrokh F. Shariat20

  1. Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; IIIrd Radiotherapy and Chemotherapy Department, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice, Poland.
  2. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Medical University of Silesia, Zabrze, Poland.
  3. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan.
  4. Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland.
  5. Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Republic of Korea.
  6. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
  7. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
  8. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  9. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, La Croix Du Sud Hospital, Quint-Fonsegrives, France.
  10. Department of Urology, Hospital Clínico San Carlos, Madrid, Spain.
  11. Unit of Urology/Division of Oncology, IRCCS Ospedale San Raffaele, Milan, Italy.
  12. Department of Urology, St Antonius Hospital, Utrecht, The Netherlands.
  13. Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
  14. Department of Radiotherapy, ICO René Gauducheau, Saint-Herblain, France.
  15. Department of Radiation Oncology, Oncological Institute of Southern Switzerland (IOSI-EOC), Bellinzona, Switzerland.
  16. Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  17. Department of Radiation Oncology, Brigham and Women's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  18. Department of Radiation Oncology, Iridium Network, Wilrijk, Belgium.
  19. Department of Urology, La Croix Du Sud Hospital, Quint-Fonsegrives, France.
  20. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Division of Urology, Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University of Texas Southwestern, Dallas, TX, USA.
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