Genomic classifiers in personalized prostate cancer radiotherapy approaches - a systematic review and future perspectives based on international consensus.

Current risk-stratification systems for prostate cancer (PCa) do not sufficiently reflect the disease heterogeneity. Genomic classifiers (GC) enable improved risk-stratification after surgery, but less data exists for patients treated with definitive radiotherapy (RT) or RT in oligo-/metastatic disease stages. In order to guide future perspectives of GCs for RT, we conducted (i) a systematic review on the evidence of GCs for patients treated with RT and (ii) a survey of experts using the DELPHI method, addressing the role of GCs in personalized treatments to identify relevant fields of future clinical and translational research.

We performed a systematic review and screened ongoing clinical trials on "clinicaltrials.gov". Based on these results a multidisciplinary international team of experts received an adapted DELPHI method survey. 31 and 30 experts answered round 1 and round 2, respectively. Questions with ≥ 75% agreement were considered as relevant and included into the qualitative synthesis.

Evidence for GCs as predictive biomarkers is mainly available to the postoperative RT setting. Validation of GCs as prognostic markers in the definitive RT settings is emerging. Experts used GCs in PCa patients with extensive metastases (30%), in postoperative settings (27%) and newly diagnosed PCa (23%). 47% of experts do not currently use GCs in clinical practice. Expert consensus demonstrates that GCs are promising tools to improve risk-stratification in primary and oligo-/metastatic patients in addition to existing classifications. Experts were convinced that GCs might guide treatment decisions in terms of RT-field definition and intensification/de-intensification in various disease stages.

This work confirms the value of GCs and the promising evidence of GC utility in the setting of RT. Additional studies of GCs as prognostic biomarkers are anticipated and form the basis for future studies addressing predictive capabilities of GCs to optimize RT and systemic therapy. The expert consensus points out future directions for GC research in the management of PCa.

International journal of radiation oncology, biology, physics. 2022 Dec 31 [Epub ahead of print]

Simon K B Spohn, Cédric Draulans, Amar U Kishan, Daniel Spratt, Ashley Ross, Tobias Maurer, Derya Tilki, Alejandro Berlin, Pierre Blanchard, Sean Collins, Peter Bronsert, Ronald Chen, Alan Dal Pra, Gert de Meerleer, Thomas Eade, Karin Haustermans, Tobias Hölscher, Stefan Höcht, Pirus Ghadjar, Elai Davicioni, Matthias Heck, Linda G W Kerkmeijer, Simon Kirste, Nikolaos Tselis, Phuoc T Tran, Michael Pinkawa, Pascal Pommier, Constantinos Deltas, Nina-Sophie Schmidt-Hegemann, Thomas Wiegel, Thomas Zilli, Alison C Tree, Xuefeng Qiu, Vedang Murthy, Jonathan I Epstein, Christian Graztke, Xin Gao, Anca L Grosu, Sophia C Kamran, Constantinos Zamboglou

Department of Radiation Oncology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK). Partner Site Freiburg, Freiburg, Germany; Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: ., Department of Radiation Oncology, University Hospitals Leuven, Belgium; Department of Oncology, KU Leuven, Belgium., Department of Radiation Oncology; Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA., Department of Radiation Oncology, UH Seidman Cancer Center, Case Western Reserve University, USA., Department of Urology, Northwestern Feinberg School of Medicine, USA., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, Koc University Hospital, Istanbul, Turkey., Department of Radiation Oncology, Temerty Faculty of Medicine, University of Toronto; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada., Department of Radiation Oncology, Gustave Roussy, Oncostat U1018, Inserm, Paris-Saclay University, Villejuif, France., Department of Radiation Medicine, Medstar Georgetown University Hospital, Washington, DC USA., Institute for Surgical Pathology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Department of Radiation Oncology, University of Kansas Cancer Center, Kansas City, KS 66160, USA., Department of Radiation Oncology, University of Miami, Miller School of Medicine, USA., Northern Sydney Cancer Centre, Radiation Oncology Unit, Royal North Shore Hospital, Sydney, New South Wales, Australia., Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany., Xcare Practices Dept. Radiotherapy, Saarlouis, Germany., Department of Radiation Oncology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin., Veracyte, Inc, San Diego, CA, USA., Department of Urology, Rechts der Isar Medical Center, Technical University of Munich, Germany., Department of Radiation Oncology, Radboud University Medical Center, The Netherlands., Department of Radiation Oncology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK). Partner Site Freiburg, Freiburg, Germany., Department of Radiation Oncology, University Hospital Johann Wolfgang Goethe University, Frankfurt, Germany., Department of Radiation Oncology, University of Maryland, USA., Department of Radiation Oncology, MediClin Robert Janker Klinik Bonn, Germany., Department of Radiation Oncology, Centre Léon Bérard, Lyon, France., Molecular Medicine Research Center and Laboratory of Molecular and Medical Genetics, Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus., Department of Radiation Oncology, University Hospital LMU Munich, Munich, Germany., Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany., Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland., Department of Radiotherapy, The Royal Marsden Hospital and the Institute of Cancer Research, London, UK., Department of Urology, Medical School of Nanjing University, Affiliated Drum Tower Hospital, Nanjing, China., Department of Radiation Oncology, ACTREC, Tata Memorial Centre, Homi Bhabha National University, India., Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Department of Urology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Department of Internal Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA., Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard, Cambridge, MA., Department of Radiation Oncology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK). Partner Site Freiburg, Freiburg, Germany; Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Oncology Center, European University of Cyprus, Limassol, Cyprus.