Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The current landscape of stereotactic body radiation therapy for metastatic castration-resistant prostate cancer

Prostate Cancer and Prostatic Diseases volume 28, pages 546–556 (2025)Cite this article

Subjects

Abstract

Background

The onset of castration-resistance is associated with dismal outcomes in patients with prostate cancer (PCa). Metastasis directed therapy has been investigated in multiple disease settings and may improve outcomes in selected patients. Our systematic review aims to summarize evidence with stereotactic body radiotherapy (SBRT) in castration-resistant prostate cancer (CRPC).

Methods

The literature search was performed on March 2024, on Pubmed, using the keywords “SBRT” AND “CRPC”, and “stereotactic ablative radiotherapy (SABR)” AND “CRPC”. This search retrieved a total of 108 articles, 19 were included.

Results

The literature is largely dominated by retrospective series. In men with metachronous oligoprogression, SBRT with androgen receptor pathway inhibitor significantly increased progression-free survival (PFS) including biochemical progression-free survival in a randomized phase II trial (hazard ratio of 0.35, p < 0.001). In patients continuing ADT, the bPFS ranged between 9.5 months to 17.9 months, and next systemic treatment-free survival (NEST-FS) reached up to 2 years. In men with induced oligoprogression, SBRT enabled NEST-FS up to 3 years. SBRT was well tolerated, with less than 5% grade 3 toxicity reported across studies.

Conclusion

In the population of patients with oligometastatic CRPC, SBRT enables long-term biochemical response and PFS. In the oligoprogressive setting, SBRT could be integrated to prolong the duration and efficacy of systemic therapies. Nevertheless, the level of evidence remains very low and inclusion within prospective trials remain the preferred option for this population of patients.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Flow chart of the study.
Fig. 2: Implementation of SBRT for oligoprogressive CRPC.
Fig. 3: Evolution of the consensus in the CRPC setting.

Similar content being viewed by others

References

  1. Dutt SS, Gao AC. Molecular mechanisms of castration-resistant prostate cancer progression. Future Oncol. 2009;5:1403–13.

    Article  PubMed  CAS  Google Scholar 

  2. Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide and overall survival in prostate cancer. Eur Urol. 2021;79:150–8.

    Article  PubMed  CAS  Google Scholar 

  3. Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF, et al. Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2020;382:2197–206.

    Article  PubMed  CAS  Google Scholar 

  4. Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020;383:1040–9.

    Article  PubMed  CAS  Google Scholar 

  5. Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PFA, Sternberg CN, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16:152–60.

    Article  PubMed  CAS  Google Scholar 

  6. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424–33.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–12.

    Article  PubMed  CAS  Google Scholar 

  8. de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels J-P, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376:1147–54.

    Article  PubMed  Google Scholar 

  9. Nuhn P, De Bono JS, Fizazi K, Freedland SJ, Grilli M, Kantoff PW, et al. Update on systemic prostate cancer therapies: management of metastatic castration-resistant prostate cancer in the era of precision oncology. Eur Urol. 2019;75:88–99.

    Article  PubMed  Google Scholar 

  10. Guckenberger M, Lievens Y, Bouma AB, Collette L, Dekker A, deSouza NM, et al. Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation. Lancet Oncol. 2020;21:e18–28.

    Article  PubMed  Google Scholar 

  11. Lievens Y, Guckenberger M, Gomez D, Hoyer M, Iyengar P, Kindts I, et al. Defining oligometastatic disease from a radiation oncology perspective: an ESTRO-ASTRO consensus document. Radiother Oncol. 2020;148:157–66.

    Article  PubMed  Google Scholar 

  12. Hannan R, Christensen M, Hammers H, Christie A, Paulman B, Lin D, et al. Phase II trial of stereotactic ablative radiation for oligoprogressive metastatic kidney cancer. Eur Urol Oncol. 2022;5:216–24.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Cheung P, Patel S, North SA, Sahgal A, Chu W, Soliman H, et al. Stereotactic radiotherapy for oligoprogression in metastatic renal cell cancer patients receiving tyrosine kinase inhibitor therapy: a phase 2 prospective multicenter study. Eur Urol. 2021;80:693–700.

    Article  PubMed  CAS  Google Scholar 

  14. Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence (STOMP): five-year results of a randomized phase II trial. J Clin Oncol. 2020;38:10.

    Article  Google Scholar 

  15. Phillips R, Shi WY, Deek M, Radwan N, Lim SJ, Antonarakis ES, et al. Outcomes of observation vs stereotactic ablative radiation for oligometastatic prostate cancer: the ORIOLE phase 2 randomized clinical trial. JAMA Oncol. 2020;6:650.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Harrow S, Palma DA, Olson R, Gaede S, Louie AV, Haasbeek C, et al. Stereotactic radiation for the comprehensive treatment of oligometastases (SABR-COMET)—extended long-term outcomes. Int J Radiat Oncol Biol Phys. 2022;114:611–6.

    Article  PubMed  Google Scholar 

  17. Francolini G, Allegra AG, Detti B, Di Cataldo V, Caini S, Bruni A, et al. Stereotactic body radiation therapy and abiraterone acetate for patients affected by oligometastatic castrate-resistant prostate cancer: a randomized phase II trial (ARTO). J Clin Oncol. 2023;41:5561–8.

    Article  PubMed  CAS  Google Scholar 

  18. Pan J, Wei Y, Zhang T, Liu C, Hu X, Zhao J, et al. Stereotactic radiotherapy for lesions detected via 68Ga-prostate-specific membrane antigen and 18F-fluorodexyglucose positron emission tomography/computed tomography in patients with nonmetastatic prostate cancer with early prostate-specific antigen progression on androgen deprivation therapy: a prospective single-center study. Eur Urol Oncol. 2022;5:420–7.

    Article  PubMed  Google Scholar 

  19. Henkenberens C, Derlin T, Bengel F, Ross TL, Kuczyk MA, Giordano FA, et al. Efficacy of PSMA PET-guided radiotherapy for oligometastatic castrate-resistant prostate cancer. Front Oncol. 2021;11:664225.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Onal C, Ozyigit G, Oymak E, Guler OC, Tilki B, Hurmuz P, et al. Stereotactic radiotherapy to oligoprogressive lesions detected with 68Ga-PSMA-PET/CT in castration-resistant prostate cancer patients. Eur J Nucl Med Mol Imaging. 2021;48:3683–92.

    Article  PubMed  CAS  Google Scholar 

  21. Lohaus F, Zöphel K, Löck S, Wirth M, Kotzerke J, Krause M, et al. Can local ablative radiotherapy revert castration-resistant prostate cancer to an earlier stage of disease? Eur Urol. 2019;75:548–51.

    Article  PubMed  Google Scholar 

  22. Berghen C, Joniau S, Ost P, Poels K, Everaerts W, Decaestecker K, et al. Progression-directed therapy for oligoprogression in castration-refractory prostate cancer. Eur Urol Oncol. 2021;4:305–9.

    Article  PubMed  Google Scholar 

  23. Zhang H, Orme JJ, Abraha F, Stish BJ, Lowe VJ, Lucien F, et al. Phase II evaluation of stereotactic ablative radiotherapy (SABR) and immunity in 11C-Choline-PET/CT–identified oligometastatic castration-resistant prostate Cancer. Clin Cancer Res. 2021;27:6376–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Chamois J, Septans AL, Schipman B, Gross E, Blanchard N, Passerat V, et al. Metastases-directed radiotherapy in castration resistant oligo metastatic prostate cancer: a multicentric retrospective study from the French group COLib. Clin Transl Radiat Oncol. 2024;46:100762.

    PubMed  PubMed Central  CAS  Google Scholar 

  25. Tsai CJ, Yang JT, Shaverdian N, Patel J, Shepherd AF, Eng J, et al. Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study. Lancet. 2024;403:171–82.

    Article  PubMed  Google Scholar 

  26. Greco C, Pares O, Pimentel N, Louro V, Morales J, Nunes B, et al. Phenotype-oriented ablation of oligometastatic cancer with single dose radiation therapy. Int J Radiat Oncol Biol Phys. 2019;104:593–603.

    Article  PubMed  Google Scholar 

  27. Rans K, Joniau S, Berghen C, Goffin K, Dumez H, Haustermans K, et al. Progression-directed therapy in oligoprogressive castration-resistant prostate cancer: final results from the prospective, single-arm, phase 2 MEDCARE trial. Eur Urol Oncol. 2024. https://doi.org/10.1016/j.euo.2024.04.003.

  28. Pezzulla D, Macchia G, Cilla S, Buwenge M, Ferro M, Bonome P, et al. Stereotactic body radiotherapy to lymph nodes in oligoprogressive castration-resistant prostate cancer patients: a post hoc analysis from two phase I clinical trials. Clin Exp Metastasis. 2021;38:519–26.

    Article  PubMed  CAS  Google Scholar 

  29. Triggiani L, Mazzola R, Magrini SM, Ingrosso G, Borghetti P, Trippa F, et al. Metastasis-directed stereotactic radiotherapy for oligoprogressive castration-resistant prostate cancer: a multicenter study. World J Urol. 2019;37:2631–7.

    Article  PubMed  CAS  Google Scholar 

  30. La Vecchia M, Fazio I, Borsellino N, Lo Casto A, Galanti D. Stereotactic body radiotherapy in oligoprogressive metastatic castration-resistant prostate cancer during abiraterone or enzalutamide. Tumor J. 2023;109:413–7.

    Article  Google Scholar 

  31. Ingrosso G, Detti B, Fodor A, Caini S, Borghesi S, Triggiani L, et al. Stereotactic ablative radiotherapy in castration-resistant prostate cancer patients with oligoprogression during androgen receptor-targeted therapy. Clin Transl Oncol. 2021;23:1577–84. https://doi.org/10.1007/s12094-021-02553-5.

    Article  PubMed  CAS  Google Scholar 

  32. Onal C, Kose F, Ozyigit G, Aksoy S, Oymak E, Muallaoglu S, et al. Stereotactic body radiotherapy for oligoprogressive lesions in metastatic castration-resistant prostate cancer patients during abiraterone/enzalutamide treatment. Prostate. 2021;81:543–52.

    Article  PubMed  CAS  Google Scholar 

  33. Baron D, Pasquier D, Pace-Loscos T, Vandendorpe B, Schiappa R, Ortholan C, et al. Stereotactic body radiation therapy to postpone systemic therapy escalation for castration-resistant prostate cancer: a multicenter retrospective analysis. Clin Transl Radiat Oncol. 2024;45:100710.

    PubMed  CAS  Google Scholar 

  34. Franzese C, Perrino M, Marzo MA, Badalamenti M, Baldaccini D, D’Agostino G, et al. Oligoprogressive castration-resistant prostate cancer treated with metastases-directed stereotactic body radiation therapy: predictive factors for patients’ selection. Clin Exp Metastasis. 2022;39:449–57.

    Article  PubMed  CAS  Google Scholar 

  35. Deek MP, Taparra K, Phillips R, Velho PI, Gao RW, Deville C, et al. Metastasis-directed therapy prolongs efficacy of systemic therapy and improves clinical outcomes in oligoprogressive castration-resistant prostate cancer. Eur Urol Oncol. 2021;4:447–55.

    Article  PubMed  Google Scholar 

  36. de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020;382:2091–102.

    Article  PubMed  Google Scholar 

  37. Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385:1091–103.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Abida W, Cheng ML, Armenia J, Middha S, Autio KA, Vargas HA, et al. Analysis of the prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade. JAMA Oncol. 2019;5:471–8.

    Article  PubMed  Google Scholar 

  39. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366. https://doi.org/10.1056/NEJMoa1200690.

  40. Beer TM, Kwon ED, Drake CG, Fizazi K, Logothetis C, Gravis G, et al. Randomized, double-blind, phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naive castration-resistant prostate cancer. J Clin Oncol. 2017;35:40–7.

    Article  PubMed  CAS  Google Scholar 

  41. Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJM, et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15:700–12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Kwan EM, Spain L, Anton A, Gan CL, Garrett L, Chang D, et al. Avelumab combined with stereotactic ablative body radiotherapy in metastatic castration-resistant prostate cancer: the phase 2 ICE-PAC clinical trial. Eur Urol. 2022;81:253–62.

    Article  PubMed  CAS  Google Scholar 

  43. Fakhrejahani F, Madan RA, Dahut WL, Karzai F, Cordes LM, Schlom J, et al. Avelumab in metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2017;35:159.

    Article  Google Scholar 

  44. Hannan R, Dohopolski MJ, Pop LM, Mannala S, Watumull L, Mathews D, et al. Phase II trial of sipuleucel-T and stereotactic ablative body radiation for patients with metastatic castrate-resistant prostate cancer. Biomedicines. 2022;10:1419.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22.

    Article  PubMed  CAS  Google Scholar 

  46. Cornford P, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, et al. EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer. Part II—2020 update: treatment of relapsing and metastatic prostate cancer. Eur Urol. 2021;79:263–82.

    Article  PubMed  CAS  Google Scholar 

  47. Smith MR, Kabbinavar F, Saad F, Hussain A, Gittelman MC, Bilhartz DL, et al. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol. 2005;23:2918–25.

    Article  PubMed  Google Scholar 

  48. James ND, Spears MR, Clarke NW, Dearnaley DP, De Bono JS, Gale J, et al. Survival with newly diagnosed metastatic prostate cancer in the ‘Docetaxel Era’: data from 917 patients in the control arm of the STAMPEDE trial (MRC PR08, CRUK/06/019). Eur Urol. 2015;67:1028–38.

    Article  PubMed  Google Scholar 

  49. Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34:1402–18.

    Article  PubMed  PubMed Central  Google Scholar 

  50. D’Angelillo RM, Francolini G, Ingrosso G, Ravo V, Triggiani L, Magli A, et al. Consensus statements on ablative radiotherapy for oligometastatic prostate cancer: a position paper of Italian Association of Radiotherapy and Clinical Oncology (AIRO). Crit Rev Oncol Hematol. 2019;138:24–8.

    Article  PubMed  Google Scholar 

  51. Zilli T, Achard V, Dal Pra A, Schmidt-Hegemann N, Jereczek-Fossa BA, Lancia A, et al. Recommendations for radiation therapy in oligometastatic prostate cancer: an ESTRO-ACROP Delphi consensus. Radiother Oncol. 2022;176:199–207.

    Article  PubMed  Google Scholar 

  52. Roach PJ, Francis R, Emmett L, Hsiao E, Kneebone A, Hruby G, et al. The impact of 68 Ga-PSMA PET/CT on management intent in prostate cancer: results of an Australian Prospective Multicenter Study. J Nucl Med. 2018;59:82–8.

    Article  PubMed  CAS  Google Scholar 

  53. Fendler WP, Weber M, Iravani A, Hofman MS, Calais J, Czernin J, et al. Prostate-specific membrane antigen ligand positron emission tomography in men with nonmetastatic castration-resistant prostate cancer. Clin Cancer Res. 2019;25:7448–54.

    Article  PubMed  CAS  Google Scholar 

  54. Chen W, Li L, Ji S, Song X, Lu W, Zhou T. Evaluation of potential surrogate endpoints for prediction of overall survival in patients with castration-resistant prostate cancer: trial-level meta-analysis. Eur J Clin Pharm. 2019;75:1521–32.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Therapy, Centre Eugène Marquis, Rennes, France

    Jennifer Le Guevelou & Renaud De Crevoisier

  2. Department of Radiation Therapy, ARNAS Civico Palermo, Palermo, Italy

    Francesco Cuccia & Giuseppe Ferrera

  3. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France

    Ronan Flippot

  4. Department of Radiation Therapy, Institut Gustave Roussy, Villejuif, France

    Mario Terlizzi

  5. Department of Radiation Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland

    Thomas Zilli

  6. Università della Svizzera Italiana, Lugano, Switzerland

    Thomas Zilli

  7. Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Thomas Zilli

  8. Department of Radiation Oncology, Centre Antoine Lacassagne, University Côte d’Azur, Nice, France

    Jean-Michel Hannoun-Levi

  9. Department of Radiation Oncology, Institut de Cancérologie de l’Ouest, Nantes, France

    Stephane Supiot

  10. Department of Radiation Oncology, Institut Bergonié, Bordeaux, France

    Paul Sargos

  11. Academic Department of Radiation Oncology, Centre Oscar Lambret, Lille, France

    David Pasquier

  12. Lille University, CRIStAL UMR CNRS 9189, Lille, France

    David Pasquier

Authors
  1. Jennifer Le Guevelou
    View author publications

    Search author on:PubMed Google Scholar

  2. Francesco Cuccia
    View author publications

    Search author on:PubMed Google Scholar

  3. Ronan Flippot
    View author publications

    Search author on:PubMed Google Scholar

  4. Giuseppe Ferrera
    View author publications

    Search author on:PubMed Google Scholar

  5. Mario Terlizzi
    View author publications

    Search author on:PubMed Google Scholar

  6. Thomas Zilli
    View author publications

    Search author on:PubMed Google Scholar

  7. Renaud De Crevoisier
    View author publications

    Search author on:PubMed Google Scholar

  8. Jean-Michel Hannoun-Levi
    View author publications

    Search author on:PubMed Google Scholar

  9. Stephane Supiot
    View author publications

    Search author on:PubMed Google Scholar

  10. Paul Sargos
    View author publications

    Search author on:PubMed Google Scholar

  11. David Pasquier
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Jennifer Le Guevelou: conceived and designed the analysis, collected the data, contributed in data analysis, contributed in the writing process; Francesco Cuccia: conceived and designed the analysis, collected the data, contributed in data analysis, contributed in the writing process; Ronan Flippot: contributed in data analysis, contributed in the writing process; Giuseppe Ferrera: contributed in data analysis, contributed in the writing process; Mario Terlizzi: contributed in data analysis, contributed in the writing process; Thomas Zilli: contributed in data analysis, contributed in the writing process; Renaud De Crevoisier: contributed in data analysis, contributed in the writing process; Jean-Michel Hannoun-Levi: contributed in data analysis, contributed in the writing process; Stephane Supiot: contributed in data analysis, contributed in the writing process; Paul Sargos: contributed in data analysis, contributed in the writing process; David Pasquier: conceived and designed the analysis, contributed in data analysis, contributed in the writing process.

Corresponding author

Correspondence to Jennifer Le Guevelou.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Le Guevelou, J., Cuccia, F., Flippot, R. et al. The current landscape of stereotactic body radiation therapy for metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 28, 546–556 (2025). https://doi.org/10.1038/s41391-024-00862-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41391-024-00862-8

This article is cited by

Search

Advanced search

Quick links