Skip to main content

Advertisement

SpringerLink
Log in

Gleason score and the risk of cause-specific and all-cause mortality following radiation with or without 6 months of androgen deprivation therapy for men with unfavorable-risk prostate cancer

  • Original Research
  • Published:
Journal of Radiation Oncology

Abstract

Purpose

We evaluated whether a differential impact of adding 6 months of androgen deprivation (ADT) to radiation therapy (RT) on all-cause (ACM), prostate cancer-specific (PCSM), and other-cause mortality (OCM) in men with unfavorable-risk prostate cancer (PC) exists within Gleason score (GS) subgroups.

Methods and materials

Individual patient data from 743 men with unfavorable-risk PC from two randomized ADT trials were utilized. Competing risks and Cox regression were used to determine whether adding 6 months of ADT to RT significantly impacted PCSM, OCM, and ACM within GS subgroups.

Results

Men with GS 9/10 versus ≤8 were significantly more likely to be over 75 (23.3 versus 12.7 %; p = 0.03). At a median follow-up of 11.93 and 11.81 years in the 683 and 60 patients with GS ≤8 and GS 9/10, 315 (46.1 %) and 44 (73.1 %) died, respectively. ADT in men with GS ≤8 was associated with significantly decreased ACM (adjusted hazard ratio (AHR) 0.66; 95 % confidence interval: 0.52–0.82; p < 0.001) and PCSM (0.43; 0.28–0.66; p < 0.001) but no significant difference in OCM (0.90; 0.68–1.17; p = 0.43) Among men with GS 9/10 PC ADT significantly reduced PCSM (0.33; 0.11–0.99; p = 0.048) but not ACM (0.79; 0.38–1.61; p = 0.51) and increased OCM (2.16; 0.81–5.79; p = 0.12), resulting in opposite effects of ADT on OCM by the GS subgroup such that the relative AHR of OCM in GS 9/10 versus ≤8 was nearly significantly increased (2.42 [0.87,6.71]; p = 0.09).

Conclusion

While ADT reduced PCSM risk overall, survival was not prolonged in men with GS 9/10 due to ADT-driven increased OCM, which supports the hypothesis that older men with significant comorbidity may not experience prolonged survival when ADT is added to RT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Pierorazio PM, Walsh PC, Partin AW, Epstein JI (2013) Prognostic Gleason grade grouping: data based on the modified Gleason scoring system. BJU Int 111:753–60. doi:10.1111/j.1464-410X.2012.11611.x

    Article  PubMed  PubMed Central  Google Scholar 

  2. D’Amico AV, Whittington R, Malkowicz SB et al (1999) Pretreatment nomogram for prostate-specific antigen recurrence after radical prostatectomy or external-beam radiation therapy for clinically localized prostate cancer. J Clin Oncol 17:168–72

    PubMed  Google Scholar 

  3. Gleason DF, Mellinger GT (1974) Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol 111:58–64

    CAS  PubMed  Google Scholar 

  4. Rusthoven CG, Waxweiler TV, DeWitt PE et al (2015) Gleason stratifications prognostic for survival in men receiving definitive external beam radiation therapy for localized prostate cancer. Urol Oncol 33:71.e11–9. doi:10.1016/j.urolonc.2014.07.010

    Article  PubMed  Google Scholar 

  5. Bostwick DG (1994) Gleason grading of prostatic needle biopsies. Correlation with grade in 316 matched prostatectomies. Am J Surg Pathol 18:796–803

    Article  CAS  PubMed  Google Scholar 

  6. National Comprehensive Cancer Network (2014) NCCN clinical practice guidelines in oncology: prostate cancer., http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf

    Google Scholar 

  7. D’Amico AV, Whittington R, Malkowicz SB et al (1998) Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 280:969–74

    Article  PubMed  Google Scholar 

  8. Warde P, Mason M, Ding K et al (2011) Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet 378:2104–11. doi:10.1016/S0140-6736(11)61095-7

    Article  PubMed  PubMed Central  Google Scholar 

  9. Widmark A, Klepp O, Solberg A et al (2009) Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet 373:301–8. doi:10.1016/S0140-6736(08)61815-2

    Article  CAS  PubMed  Google Scholar 

  10. Bolla M, Van Tienhoven G, Warde P et al (2010) External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol 11:1066–73. doi:10.1016/S1470-2045(10)70223-0

    Article  CAS  PubMed  Google Scholar 

  11. D’Amico AV, Chen M-H, Renshaw AA et al (2008) Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA 299:289–95. doi:10.1001/jama.299.3.289

    PubMed  Google Scholar 

  12. Denham JW, Steigler A, Lamb DS et al (2011) Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol 12:451–9. doi:10.1016/S1470-2045(11)70063-8

    Article  CAS  PubMed  Google Scholar 

  13. Bolla M, de Reijke TM, Van Tienhoven G et al (2009) Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 360:2516–27. doi:10.1056/NEJMoa0810095

    Article  CAS  PubMed  Google Scholar 

  14. Zapatero A, Guerrero A, Maldonado X et al (2015) High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol 16:320–7. doi:10.1016/S1470-2045(15)70045-8

    Article  CAS  PubMed  Google Scholar 

  15. Horwitz EM, Bae K, Hanks GE et al (2008) Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol 26:2497–504. doi:10.1200/JCO.2007.14.9021

    Article  CAS  PubMed  Google Scholar 

  16. Denham JW, Joseph D, Lamb DS et al (2014) Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): an open-label, randomised, phase 3 factorial. Lancet Oncol 15:1076–89. doi:10.1016/S1470-2045(14)70328-6

    Article  CAS  PubMed  Google Scholar 

  17. Nabid A, Carrier N, Martin A-G et al (2013) Duration of androgen deprivation therapy in high-risk prostate cancer: a randomized trial. ASCO Meet Abstr 31:LBA4510

    Google Scholar 

  18. Thompson IM, Ankerst DP, Chi C et al (2006) Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. J Natl Cancer Inst 98:529–34. doi:10.1093/jnci/djj131

    Article  PubMed  Google Scholar 

  19. Piccirillo JF, Vlahiotis A, Barrett LB et al (2008) The changing prevalence of comorbidity across the age spectrum. Crit Rev Oncol Hematol 67:124–32. doi:10.1016/j.critrevonc.2008.01.013

    Article  PubMed  PubMed Central  Google Scholar 

  20. Extermann M (2000) Measurement and impact of comorbidity in older cancer patients. Crit Rev Oncol Hematol 35:181–200

    Article  CAS  PubMed  Google Scholar 

  21. Jousilahti P, Vartiainen E, Tuomilehto J, Puska P (1999) Sex, age, cardiovascular risk factors, and coronary heart disease: a prospective follow-up study of 14 786 middle-aged men and women in Finland. Circulation 99:1165–1172. doi:10.1161/01.CIR.99.9.1165

    Article  CAS  PubMed  Google Scholar 

  22. Tsai HK, D’Amico AV, Sadetsky N et al (2007) Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. J Natl Cancer Inst 99:1516–24. doi:10.1093/jnci/djm168

    Article  PubMed  Google Scholar 

  23. D’Amico AV, Denham JW, Crook J et al (2007) Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. J Clin Oncol 25:2420–5. doi:10.1200/JCO.2006.09.3369

    Article  PubMed  Google Scholar 

  24. Saigal CS, Gore JL, Krupski TL et al (2007) Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer 110:1493–500. doi:10.1002/cncr.22933

    Article  CAS  PubMed  Google Scholar 

  25. Nanda A, Chen M-H, Braccioforte MH et al (2009) Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction. JAMA 302:866–73. doi:10.1001/jama.2009.1137

    Article  CAS  PubMed  Google Scholar 

  26. O’Farrell S, Garmo H, Holmberg L et al (2015) Risk and timing of cardiovascular disease after androgen-deprivation therapy in men with prostate cancer. J Clin Oncol 33:1243–51. doi:10.1200/JCO.2014.59.1792

    Article  PubMed  Google Scholar 

  27. D’Amico AV, Chen M-H, Renshaw A et al (2015) Long-term follow-up of a randomized trial of radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA 314:1291–3. doi:10.1001/jama.2015.8577

    Article  PubMed  Google Scholar 

  28. Beahrs O, Henson D, Hutter R (1992) American Joint Committee on Cancer: manual for staging cancer, 4th edn. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  29. Hollander M, Wolfe D (1999) Nonparametric statistical methods, 2nd edn. Wiley, New York

    Google Scholar 

  30. Agresti A (2013) Inference for two-way contingency tables. Categ. Data anal, 3rd edn. Wiley, New York, pp 69–112

    Google Scholar 

  31. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481. doi:10.1080/01621459.1958.10501452

    Article  Google Scholar 

  32. Gaynor J, Feuer E, Tan C (1993) On the use of cause-specific failure and conditional failure probabilities: examples from clinical oncology data. J Am Stat Assoc 88:400–409. doi:10.2307/2290318

  33. Kutner M, Nachtshein C, Neter J (2005) Analysis of factor level means. Appl. Linear regres. Model, 5th edn. McGraw-Hill/Irwin, New York, pp 756–759

    Google Scholar 

  34. Klein J, Moeschberger M (1997) Survival analysis: techniques for censored and truncated data (statistics for biology and health). Springer, New York

    Book  Google Scholar 

  35. Keating NL, O’Malley AJ, Smith MR (2006) Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 24:4448–56. doi:10.1200/JCO.2006.06.2497

    Article  CAS  PubMed  Google Scholar 

  36. Traish AM, Saad F, Feeley RJ, Guay A (2009) The dark side of testosterone deficiency: III. Cardiovascular disease. J Androl 30:477–94. doi:10.2164/jandrol.108.007245

    Article  CAS  PubMed  Google Scholar 

  37. Scher HI, Fizazi K, Saad F et al (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367:1187–97. doi:10.1056/NEJMoa1207506

    Article  CAS  PubMed  Google Scholar 

  38. Beer TM, Armstrong AJ, Rathkopf DE et al (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371:424–33. doi:10.1056/NEJMoa1405095

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Harvard Radiation Oncology Program, Brigham and Women’s Hospital, 75 Francis Street, ASB1-L2, Boston, MA, 02115, USA

    Laura E. G. Warren

  2. Department of Statistics, University of Connecticut, Storrs, Connecticut, USA

    Ming-Hui Chen

  3. School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia

    James W. Denham & Allison B. Steigler

  4. Department of Pathology, Baptist Hospital of Miami, Miami, FL, USA

    Andrew A. Renshaw

  5. Department of Radiation Oncology, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    Marian Loffredo & Anthony V. D’Amico

  6. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    Philip W. Kantoff

Authors
  1. Laura E. G. Warren
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ming-Hui Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James W. Denham
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Allison B. Steigler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrew A. Renshaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marian Loffredo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Philip W. Kantoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anthony V. D’Amico
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laura E. G. Warren.

Ethics declarations

Funding

None.

Conflict of interest

Laura Warren, Ming-Hui Chen, James Denham, Allison Steigler, Andrew Renshaw, Marian Loffredo, Philip Kantoff, and Anthony D’Amico declare that they have no conflict of interest.

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent

Informed consent was obtained from all patients included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Warren, L.E.G., Chen, MH., Denham, J.W. et al. Gleason score and the risk of cause-specific and all-cause mortality following radiation with or without 6 months of androgen deprivation therapy for men with unfavorable-risk prostate cancer. J Radiat Oncol 5, 301–308 (2016). https://doi.org/10.1007/s13566-016-0260-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13566-016-0260-9

Keywords

Search

Navigation