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.

  • Original Article
  • Published:

Clinical Research

Select men benefit from androgen deprivation therapy delivered with salvage radiation therapy after prostatectomy

Prostate Cancer and Prostatic Diseases volume 20, pages 389–394 (2017)Cite this article

Subjects

Abstract

Background:

Which men benefit most from adding androgen deprivation therapy (ADT) to salvage radiation therapy (SRT) after prostatectomy has not clearly been defined; therefore, we evaluated the impact of ADT to SRT on failure-free survival (FFS) in men with a rising or persistent PSA after prostatectomy.

Methods:

We identified 332 men who received SRT after prostatectomy from 1987 to 2010. Recursive partitioning analysis (RPA) identified favorable, intermediate and unfavorable groups based on the risk of failure after SRT alone. Kaplan–Meier and log-rank tests compared FFS with and without ADT.

Results:

Forty-three percent received SRT alone and 57% received SRT with ADT (median 6.6 months (interquartile range (IQR) 5.8–18.1) ADT). Median SRT dose was 70 Gy (IQR 70–70), and median follow-up after SRT was 6.7 years (IQR 4.5–10.8). On Cox's proportional hazard regression, ADT improved FFS (adjusted hazard ratio 0.60, 95% confidence interval: 0.42–0.86; P=0.006). RPA classified unfavorable disease as negative surgical margins (SMs) and preradiation PSA of ⩾0.5 ng ml−1. Favorable disease had neither adverse factor, and intermediate disease had one adverse factor. The addition of ADT to SRT improved 5-year FFS for men with unfavorable disease (70.3% vs 23.4%; P<0.001) and intermediate disease (69.8% vs 48.0%; P=0.003), but not for men with favorable disease (81.2% vs 78.0%; P=0.971).

Conclusions:

The addition of ADT to SRT appears to improve FFS for men with a preradiation PSA of ⩾0.5 ng ml−1 or with negative SM at prostatectomy. Men with involved surgical margins and PSA <0.5 ng ml−1 appear to be at a lower risk of failure after SRT alone and may not derive as much benefit from the administration of ADT with SRT. These results are hypothesis-generating only, and further prospective data are required to see if ADT can safely be omitted in this select group of men.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Thompson IM, Valicenti RK, Albertsen P, Davis BJ, Goldenberg SL, Hahn C et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO Guideline. J Urol 2013; 190: 441–449.

    Article  Google Scholar 

  2. Freedland SJ, Rumble RB, Finelli A, Chen RC, Slovin S, Stein MN et al. Adjuvant and salvage radiotherapy after prostatectomy: American Society of Clinical Oncology clinical practice guideline endorsement. J Clin Oncol Off J Am Soc Clin Oncol 2013; 32: 3892–3898.

    Article  Google Scholar 

  3. Pilepich MV, Winter K, Lawton CA, Krisch RE, Wolkov HB, Movsas B et al. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma—long-term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys 2005; 61: 1285–1290.

    Article  CAS  Google Scholar 

  4. D’Amico AV, Chen M-H, Renshaw AA, Loffredo M, Kantoff PW . Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA 2008; 299: 289–295.

    Article  Google Scholar 

  5. Bolla M, de Reijke TM, Van Tienhoven G, Van den Bergh ACM, Oddens J, Poortmans PMP et al. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 2009; 360: 2516–2527.

    Article  CAS  Google Scholar 

  6. Lawton CA, DeSilvio M, Roach M, Uhl V, Kirsch R, Seider M et al. An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys 2007; 69: 646–655.

    Article  Google Scholar 

  7. Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD et al. 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 Off J Am Soc Clin Oncol 2008; 26: 2497–2504.

    Article  CAS  Google Scholar 

  8. Castle KO, Hoffman KE, Levy LB, Lee AK, Choi S, Nguyen QN et al. Is androgen deprivation therapy necessary in all intermediate-risk prostate cancer patients treated in the dose escalation era? Int J Radiat Oncol Biol Phys 2013; 85: 693–699.

    Article  Google Scholar 

  9. Stephenson AJ, Scardino PT, Kattan MW, Pisansky TM, Slawin KM, Klein EA et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol 2007; 25: 2035–2041.

    Article  Google Scholar 

  10. Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM et al. Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85-31. J Clin Oncol Off J Am Soc Clin Oncol 2009; 27: 92–99.

    Article  Google Scholar 

  11. Corn BW, Winter K, Pilepich MV . Does androgen suppression enhance the efficacy of postoperative irradiation? A secondary analysis of RTOG 85-31. Radiation Therapy Oncology Group. Urology 1999; 54: 495–502.

    Article  CAS  Google Scholar 

  12. Cheung R, Kamat AM, de Crevoisier R, Allen PK, Lee AK, Tucker SL et al. Outcome of salvage radiotherapy for biochemical failure after radical prostatectomy with or without hormonal therapy. Int J Radiat Oncol Biol Phys 2005; 63: 134–140.

    Article  Google Scholar 

  13. King CR, Presti JC, Gill H, Brooks J, Hancock SL . Radiotherapy after radical prostatectomy: does transient androgen suppression improve outcomes? Int J Radiat Oncol Biol Phys 2004; 59: 341–347.

    Article  Google Scholar 

  14. Eulau SM, Tate DJ, Stamey TA, Bagshaw MA, Hancock SL . Effect of combined transient androgen deprivation and irradiation following radical prostatectomy for prostatic cancer. Int J Radiat Oncol Biol Phys 1998; 41: 735–740.

    Article  CAS  Google Scholar 

  15. Taylor N, Kelly JF, Kuban DA, Babaian RJ, Pisters LL, Pollack A . Adjuvant and salvage radiotherapy after radical prostatectomy for prostate cancer. Int J Radiat Oncol Biol Phys 2003; 56: 755–763.

    Article  CAS  Google Scholar 

  16. Morgan SC, Waldron TS, Eapen L, Mayhew LA, Winquist E, Lukka H et al. Adjuvant radiotherapy following radical prostatectomy for pathologic T3 or margin-positive prostate cancer: a systematic review and meta-analysis. Radiother Oncol J Eur Soc Ther Radiol Oncol 2008; 88: 1–9.

    Article  Google Scholar 

  17. Brockman JA, Alanee S, Vickers AJ, Scardino PT, Wood DP, Kibel AS et al. Nomogram predicting prostate cancer-specific mortality for men with biochemical recurrence after radical prostatectomy. Eur Urol 2015; 67: 1160–1167.

    Article  Google Scholar 

  18. Shipley WU, Seiferheld W, Lukka HR, Major PP, Heney NM, Grignon DJ et al. Radiation with or without antiandrogen therapy in recurrent prostate cancer. N Engl J Med 2017; 376: 417–428.

    Article  Google Scholar 

  19. Carrie C, Hasbini A, de Laroche G, Richaud P, Guerif S, Latorzeff I et al. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol 2016; 17: 747–756.

    Article  CAS  Google Scholar 

  20. Parker C, Clarke N, Logue J, Payne H, Catton C, Kynaston H et al. RADICALS (Radiotherapy and Androgen Deprivation in Combination after Local Surgery). Clin Oncol 2007; 19: 167–171.

    Article  CAS  Google Scholar 

  21. Pollack A . RTOG 0534 Protocol Information [Internet]. Available at: https://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=0534 (last accessed 9 February 2017).

  22. Stephenson AJ, Scardino PT, Kattan MW, Pisansky TM, Slawin KM, Klein EA et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol Off J Am Soc Clin Oncol 2007; 25: 2035–2041.

    Article  Google Scholar 

  23. Cadeddu JA, Partin AW, DeWeese TL, Walsh PC . Long-term results of radiation therapy for prostate cancer recurrence following radical prostatectomy. J Urol 1998; 159: 173–177-178.

    Article  CAS  Google Scholar 

  24. Macdonald OK, D’Amico AV, Sadetsky N, Shrieve DC, Carroll PR . Adjuvant radiotherapy in prostate cancer: predictors of prostate-specific antigen recurrence from the CaPSURE database. Urology 2007; 70: 106–110.

    Article  Google Scholar 

  25. Pisansky TM, Kozelsky TF, Myers RP, Hillman DW, Blute ML, Buskirk SJ et al. Radiotherapy for isolated serum prostate specific antigen elevation after prostatectomy for prostate cancer. J Urol 2000; 163: 845–850.

    Article  CAS  Google Scholar 

  26. Pearse M, Fraser-Browne C, Davis ID, Duchesne GM, Fisher R, Frydenberg M et al. A Phase III trial to investigate the timing of radiotherapy for prostate cancer with high-risk features: background and rationale of the Radiotherapy Adjuvant Versus Early Salvage (RAVES) trial. BJU Int 2014; 113 (Suppl 2): 7–12.

    Article  Google Scholar 

Download references

Acknowledgements

There were no funding sources for this work.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    E B Holliday, D A Kuban, L B Levy, P Master, S Choi, Q Nguyen, S E McGuire, U Mahmood, S J Frank & K E Hoffman

  2. American Hospital, Istanbul, Turkey

    Y Bolukbasi

Authors
  1. E B Holliday
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D A Kuban
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L B Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y Bolukbasi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P Master
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Q Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S E McGuire
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. U Mahmood
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S J Frank
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. K E Hoffman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K E Hoffman.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Holliday, E., Kuban, D., Levy, L. et al. Select men benefit from androgen deprivation therapy delivered with salvage radiation therapy after prostatectomy. Prostate Cancer Prostatic Dis 20, 389–394 (2017). https://doi.org/10.1038/pcan.2017.24

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/pcan.2017.24

This article is cited by

Search

Advanced search

Quick links