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.

  • Article
  • Clinical Research
  • Published:

Long-term outcomes of prostate radiotherapy for newly-diagnosed metastatic prostate cancer

Abstract

Background

In patients presenting with metastatic prostate cancer, the role of local therapy is evolving. Two recently reported large-scale randomized trials suggest that radiotherapy (RT) directed at the prostate improves overall survival (OS) in patients with low metastatic burden. We reviewed the experience of prostate RT in this setting at our center.

Methods

The study population consisted of men with newly-diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) referred to a comprehensive cancer center between 2005 and 2015 and treated initially with androgen deprivation therapy. Patients were eligible for inclusion if they received (1) prostate RT with biological effective dose (BED) at least that of a course of 40 Gy in 15 fractions or (2) no prostate RT. The association between receipt of prostate RT and OS was studied. OS was estimated using the Kaplan–Meier method and Cox regression was used to identify factors associated with OS.

Results

The cohort consisted of 410 patients, of whom 128 received prostate RT. Median follow-up 61.0 months. On univariate analysis, receipt of prostate RT was associated with improved OS (HR 0.59, 95% CI 0.45–0.77, p = 0.0001). Median OS in those patients receiving prostate RT was 47.4 months versus 26.3 months in those not receiving prostate RT. In a multivariate Cox model, receipt of prostate RT remained associated with improved OS (HR 0.69, 95% CI 0.50–0.94, p = 0.02). In those treated with prostate RT, increasing BED was also associated with improved OS (HR 0.87 per 10 Gy increase, 95% CI 0.76–0.99, p = 0.03).

Conclusions

This cohort represents the largest single-center experience of primary tumor-directed RT in mHSPC reported to date. In this population, receipt of prostate RT was associated with improved OS and the magnitude of the OS benefit was clinically significant. The possibility of an RT dose-response gradient in this setting merits further study.

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

Access options

Buy this article

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Culp SH, Schellhammer PF, Williams MB. Might men diagnosed with metastatic prostate cancer benefit from definitive treatment of the primary tumor? A SEER-based study. Eur Urol. 2014;65(Jun):1058–66. https://doi.org/10.1016/j.eururo.2013.11.012.

    Article  PubMed  Google Scholar 

  2. Satkunasivam R, Kim AE, Desai M, Nguyen MM, Quinn DI, Ballas L, et al. Radical prostatectomy or external beam radiation therapy vs no local therapy for survival benefit in metastatic prostate cancer: a SEER-medicare analysis. J Urol. 2015;194(Aug):378–85. https://doi.org/10.1016/j.juro.2015.02.084.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Rusthoven CG, Jones BL, Flaig TW, Crawford ED, Koshy M, Sher DJ, et al. Improved survival with prostate radiation in addition to androgen deprivation therapy for men with newly diagnosed metastatic prostate cancer. J Clin Oncol. 2016;34:2835–42. https://doi.org/10.1200/JCO.2016.67.4788. 08.

    Article  CAS  PubMed  Google Scholar 

  4. Morgan SC, Parker CC. Local treatment of metastatic cancer–killing the seed or disturbing the soil?. Nat Rev Clin Oncol. 2011;8(Jun):504–6. https://doi.org/10.1038/nrclinonc.2011.88.

    Article  PubMed  Google Scholar 

  5. Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A. et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392:2353–66. https://doi.org/10.1016/s0140-6736(18)32486-3.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Boeve LMS, Hulshof M, Vis AN, Zwinderman AH, Twisk JWR, Witjes WPJ, et al. Effect on survival of androgen deprivation therapy alone compared to androgen deprivation therapy combined with concurrent radiation therapy to the prostate in patients with primary bone metastatic prostate cancer in a prospective randomised clinical trial: data from the HORRAD trial. Eur Urol. 2019;75(Mar):410–8. https://doi.org/10.1016/j.eururo.2018.09.008.

    Article  PubMed  Google Scholar 

  7. Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26(Mar):1148–59. https://doi.org/10.1200/JCO.2007.12.4487.

    Article  PubMed  Google Scholar 

  8. Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al. (Eds.) AJCC Cancer Staging Manual. 8 ed. Chicago: Springer International Publishing; 2017. p.1032.

  9. Lévesque LE, Hanley JA, Kezouh A, Suissa S. Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes. BMJ. 2010;340(Mar):b5087 https://doi.org/10.1136/bmj.b5087.

    Article  PubMed  Google Scholar 

  10. Donovan JL, Hamdy FC, Lane JA, Mason M, Metcalfe C, Walsh E, et al. Patient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer. N. Engl J Med. 2016;375(Oct):1425–37. https://doi.org/10.1056/NEJMoa1606221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sanda MG, Dunn RL, Michalski J, Sandler HM, Northouse L, Hembroff L, et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. N. Engl J Med. 2008;358(Mar):1250–61. https://doi.org/10.1056/NEJMoa074311.

    Article  CAS  PubMed  Google Scholar 

  12. Rothwell PM. Factors that can affect the external validity of randomised controlled trials. PLoS Clin Trials. 2006;1(May):e9 https://doi.org/10.1371/journal.pctr.0010009.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M. et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N. Engl J Med. 2015;373(Aug):737–46.

    Article  CAS  Google Scholar 

  14. James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR. et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(Mar):1163–77.

    Article  CAS  Google Scholar 

  15. Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY. et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N. Engl J Med. 2017;377(Jul):352–60.

    Article  CAS  Google Scholar 

  16. James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP. et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N. Engl J Med. 2017;377(Jul):338–51.

    Article  CAS  Google Scholar 

  17. Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S. et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N. Engl J Med. 2019;381(Jul):121–31. https://doi.org/10.1056/NEJMoa1903835.

    Article  CAS  PubMed  Google Scholar 

  18. Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R. et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N. Engl J Med. 2019;381(Jul):13–24. https://doi.org/10.1056/NEJMoa1903307.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Conception and design: SCM, SM, OEH. Administrative support: SG, JC. Provision of study material or patients: SM, SCM. Collection and assembly of data: JC, SG, SCM. Data analysis and interpretation: SCM, SM, OEH. Initial paper writing: SCM. Critical review and final approval of paper: all authors.

Corresponding author

Correspondence to Scott C. Morgan.

Ethics declarations

Conflict of interest

The authors declare that they have no competing financial interests in relation to this work. Outside of this work, SCM has served in a consulting or advisory role for Astellas Pharma, Bayer, Janssen, and Tersera. Outside of this work, SM has received honoraria from Astellas Pharma, Bayer, Janssen, and Sanofi, and has received travel and accommodation support from Sanofi and Tersera. The other authors have no financial disclosures.

Additional information

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morgan, S.C., Holmes, O.E., Craig, J. et al. Long-term outcomes of prostate radiotherapy for newly-diagnosed metastatic prostate cancer. Prostate Cancer Prostatic Dis 24, 1041–1047 (2021). https://doi.org/10.1038/s41391-021-00339-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41391-021-00339-y

This article is cited by

Search

Quick links