Stephanie G C Kroeze1, Christoph Henkenberens2, Nina Sophie Schmidt-Hegemann3, Marco M E Vogel4, Simon Kirste5, Jessica Becker6, Irene A Burger7, Thorsten Derlin8, Peter Bartenstein9, Matthias Eiber10, Michael Mix11, Christian la Fougère12, Hans Christiansen2, Claus Belka13, Stephanie E Combs14, Anca L Grosu5, Arndt Christian Müller6, Matthias Guckenberger15. 1. Department of Radiation Oncology, University Hospital Zürich, Zurich, Switzerland. Electronic address: stephanie.kroeze@usz.ch. 2. Department of Radiotherapy and Special Oncology, Hannover Medical School, Hannover, Germany. 3. Department of Radiation Oncology, University Hospital LMU Munich, Munich, Germany. 4. Department of Radiation Oncology, Technical University Munich, Munich, Germany. 5. Department of Radiation Oncology, University of Freiburg, Freiburg, Germany; German Cancer Consortium Partner Site Freiburg, German Cancer Research Center, Heidelberg, Germany. 6. Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany. 7. Department of Nuclear Medicine, University Hospital Zürich, Zurich, Switzerland. 8. Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany. 9. Department of Nuclear Medicine, University Hospital LMU Munich, Munich, Germany. 10. Department of Nuclear Medicine, Technical University Munich, Munich, Germany. 11. Department of Nuclear Medicine, University of Freiburg, Freiburg, Germany. 12. Department of Nuclear Medicine, University Hospital Tübingen, Tübingen, Germany. 13. Department of Radiation Oncology, University Hospital LMU Munich, Munich, Germany; German Cancer Consortium Partner Site Munich, German Cancer Research Center, Heidelberg, Germany. 14. Department of Radiation Oncology, Technical University Munich, Munich, Germany; Institute of Innovative Radiotherapy, Oberschleissheim, Germany. 15. Department of Radiation Oncology, University Hospital Zürich, Zurich, Switzerland.
Abstract
BACKGROUND: Approximately 40-70% of biochemically recurrent prostate cancer (PCa) is oligorecurrent after prostate-specific membrane antigen (PSMA) positron emission tomography (PET) staging. Metastasis-directed radiotherapy (MDT) of PSMA-positive oligorecurrence is now frequently used, but the role of concurrent androgen deprivation therapy (ADT) remains unclear. OBJECTIVE: To determine the effect of concurrent ADT with PSMA PET-directed MDT on biochemical progression-free survival (bRFS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective multicenter study of 305 patients with biochemical recurrence and PSMA PET-positive oligorecurrence following initial curative treatment between April 2013 and January 2018. INTERVENTION: MDT with fractionated or stereotactic body radiotherapy for all PSMA-positive metastatic sites; 37.8% received concurrent ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was bRFS, which was measured using Kaplan-Meier curves and log-rank testing. Secondary outcomes were ADT-free survival, overall survival (OS), and toxicity was analyzed using the Common Terminology Criteria for Adverse Events v4.03. Univariate and multivariate analyses were performed to determine independent clinicopathological factors. RESULTS AND LIMITATIONS: The median follow-up was 16 mo (interquartile range 9-27). Some 96% of the patients initially had high-risk PCa. A median of one (range 0-19) nodal metastases and one (range 0-5) distant metastases were treated. MDT+ADT significantly improved bRFS and remained an independent factor (hazard ratio 0.28, 95% confidence interval 0.16-0.51; p<0.0001). bRFS was not significantly different between MDT+≤6 mo of ADT and MDT alone (p=0.121). Patients receiving MDT had 1- and 2-yr ADT-free survival of 93% and 83%, respectively. New therapies, most frequently MDT (23%), were required more frequently after MDT (85% vs 29%; p<0.001). Grade ≥3 acute toxicity was observed in 0.9% of patients and late toxicity in 2.3%. CONCLUSIONS: In this cohort of patients with oligorecurrent PCa, concurrent ADT with MDT improved bRFS significantly, but a large number of patients treated with MDT were spared from ADT for 2yr, although a greater need for other salvage therapies was observed. PATIENT SUMMARY: The role of concurrent androgen deprivation therapy (ADT) with radiotherapy for prostate cancer oligorecurrence identified on prostate-specific membrane antigen positron emission tomography was studied. We concluded that radiotherapy alone could prolong the time to start of ADT. However, the risk of disease progression and consequently the need for further treatments is higher after local radiotherapy alone without immediate ADT.
BACKGROUND: Approximately 40-70% of biochemically recurrent prostate cancer (PCa) is oligorecurrent after prostate-specific membrane antigen (PSMA) positron emission tomography (PET) staging. Metastasis-directed radiotherapy (MDT) of PSMA-positive oligorecurrence is now frequently used, but the role of concurrent androgen deprivation therapy (ADT) remains unclear. OBJECTIVE: To determine the effect of concurrent ADT with PSMA PET-directed MDT on biochemical progression-free survival (bRFS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective multicenter study of 305 patients with biochemical recurrence and PSMA PET-positive oligorecurrence following initial curative treatment between April 2013 and January 2018. INTERVENTION: MDT with fractionated or stereotactic body radiotherapy for all PSMA-positive metastatic sites; 37.8% received concurrent ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was bRFS, which was measured using Kaplan-Meier curves and log-rank testing. Secondary outcomes were ADT-free survival, overall survival (OS), and toxicity was analyzed using the Common Terminology Criteria for Adverse Events v4.03. Univariate and multivariate analyses were performed to determine independent clinicopathological factors. RESULTS AND LIMITATIONS: The median follow-up was 16 mo (interquartile range 9-27). Some 96% of the patients initially had high-risk PCa. A median of one (range 0-19) nodal metastases and one (range 0-5) distant metastases were treated. MDT+ADT significantly improved bRFS and remained an independent factor (hazard ratio 0.28, 95% confidence interval 0.16-0.51; p<0.0001). bRFS was not significantly different between MDT+≤6 mo of ADT and MDT alone (p=0.121). Patients receiving MDT had 1- and 2-yr ADT-free survival of 93% and 83%, respectively. New therapies, most frequently MDT (23%), were required more frequently after MDT (85% vs 29%; p<0.001). Grade ≥3 acute toxicity was observed in 0.9% of patients and late toxicity in 2.3%. CONCLUSIONS: In this cohort of patients with oligorecurrent PCa, concurrent ADT with MDT improved bRFS significantly, but a large number of patients treated with MDT were spared from ADT for 2yr, although a greater need for other salvage therapies was observed. PATIENT SUMMARY: The role of concurrent androgen deprivation therapy (ADT) with radiotherapy for prostate cancer oligorecurrence identified on prostate-specific membrane antigen positron emission tomography was studied. We concluded that radiotherapy alone could prolong the time to start of ADT. However, the risk of disease progression and consequently the need for further treatments is higher after local radiotherapy alone without immediate ADT.
Authors: Ann-Kathrin Oehus; Stephanie G C Kroeze; Nina-Sophie Schmidt-Hegemann; Marco M E Vogel; Simon Kirste; Jessica Becker; Irene A Burger; Thorsten Derlin; Peter Bartenstein; Matthias Eiber; Michael Mix; Christian la Fougère; Claus Belka; Stephanie E Combs; Anca-Ligia Grosu; Arndt-Christian Müller; Matthias Guckenberger; Hans Christiansen; Christoph Henkenberens Journal: BMC Cancer Date: 2020-04-29 Impact factor: 4.430
Authors: Christoph Henkenberens; Thorsten Derlin; Frank Bengel; Tobias L Ross; Markus A Kuczyk; Frank A Giordano; Gustavo R Sarria; Leonard Christopher Schmeel; Hans Christiansen; Christoph A J von Klot Journal: Front Oncol Date: 2021-04-19 Impact factor: 6.244
Authors: Marco M E Vogel; Sabrina Dewes; Eva K Sage; Michal Devecka; Kerstin A Eitz; Jürgen E Gschwend; Matthias Eiber; Stephanie E Combs; Kilian Schiller Journal: Front Oncol Date: 2021-07-30 Impact factor: 6.244
Authors: Marco M E Vogel; Stephanie G C Kroeze; Christoph Henkenberens; Nina-Sophie Schmidt-Hegemann; Simon Kirste; Jessica Becker; Irene A Burger; Thorsten Derlin; Peter Bartenstein; Michael Mix; Christian la Fougère; Matthias Eiber; Hans Christiansen; Claus Belka; Anca L Grosu; Arndt-Christian Müller; Matthias Guckenberger; Stephanie E Combs Journal: Eur J Nucl Med Mol Imaging Date: 2020-03-16 Impact factor: 9.236
Authors: Christoph Henkenberens; Ann-Kathrin Oehus; Thorsten Derlin; Frank Bengel; Tobias L Ross; Markus A Kuczyk; Stefan Janssen; Hans Christiansen; Christoph A J von Klot Journal: Strahlenther Onkol Date: 2020-05-12 Impact factor: 3.621
Authors: Marco M E Vogel; Sabrina Dewes; Eva K Sage; Michal Devecka; Jürgen E Gschwend; Matthias Eiber; Stephanie E Combs; Kilian Schiller Journal: Radiat Oncol Date: 2021-05-01 Impact factor: 4.309
Authors: Simon Kirste; Stephanie G C Kroeze; Christoph Henkenberens; Nina-Sophie Schmidt-Hegemann; Marco M E Vogel; Jessica Becker; Constantinos Zamboglou; Irene Burger; Thorsten Derlin; Peter Bartenstein; Juri Ruf; Christian la Fougère; Matthias Eiber; Hans Christiansen; Stephanie E Combs; Arndt-Christian Müller; Claus Belka; Matthias Guckenberger; Anca-Ligia Grosu Journal: Front Oncol Date: 2021-05-10 Impact factor: 6.244