What should be done for patients with locally advanced disease who are not suitable candidates for surgery or radiotherapy – primary androgen deprivation at diagnosis or wait until clinical progression (localized or metastatic)?

From Cancer Guidelines Wiki

What should be done for patients with locally advanced disease who are not suitable candidates for surgery or radiotherapy – primary androgen deprivation at diagnosis or wait until clinical progression (localized or metastatic)?

Choice of androgen deprivation therapy

Given the finding that there is possibly a modest benefit for use of primary ADT for locally advanced prostate cancer, it is reasonable to ask whether one therapy is better than another. Again, whilst there is extensive data dating back to the 1970s and the analysis is complicated by the reasons listed in the dot points above. If primary ADT is to be used, data would support castration. There was one RCT and two quasi-randomised trials showing a trend towards higher mortality rates with oestrogens as compared with orchidectomy at four years and longer follow-up[1][2][3][4] and RCTs suggesting a trend towards lower overall survival with anti-androgens alone when compared with medical or surgical castration11 or combined androgen blockade.[5]

This leads to the question as to whether combined androgen blockade (CAB) is better than castration alone for locally advanced disease. There is no definitive comparative trial answering this question in this patient population, with most trials comparing CAB with castration focusing on metastatic disease. Subgroup analyses for patients without evidence of metastatic disease (M0) did not show a survival benefit for combined androgen deprivation for the M0 population[6][5][7]The Prostate Cancer Trialists’ Collaborative Group[6] found a small benefit for non-steroidal anti-androgen plus castration in M0 and M1 patients combined (12% M0) but did not analyse separately the effects of adding nonsteroidal anti-androgens for men with non-metastatic disease. Notably, the steroidal anti-androgen, cyproterone plus castration group was slightly worse than castration alone for the combined group of M0 and M1. Therefore, there are no data for or against using CAB for locally advanced disease and the data that do exist suggest no survival benefit. Given the incremental toxicity with CAB, this additional therapy cannot be used without the risk of a detrimental effect on quality of life. Therefore there are no data to mandate CAB if primary ADT therapy is going to be used in patients with locally advanced prostate cancer.

Back to top

Evidence summary and recommendations

Evidence summary Level References
In terms of overall survival there are no data for or against using CAB in preference to medical or surgical castration alone as primary ADT for locally advanced prostate cancer. I, II [6], [7], [8]
If primary ADT is to be used, the data would support medical or surgical castration. II, III-1 [1], [2], [3], [4], [5], [9]

The modest benefit seen with castration alone in the two modern-era studies[10],[11] suggests castration alone can be used as a primary ADT for men with locally advanced prostate cancer. The modest benefit from CAB in the combined M0 and M1 group[6] is at the cost of increased toxicity and may or may not translate to this patient population.

Evidence-based recommendationQuestion mark transparent.png Grade
A recommendation cannot be made on the basis of the evidence currently available.
D


Back to top

References

  1. 1.0 1.1 Jordan WP Jr, Blackard CE, Byar DP. Reconsideration of orchiectomy in the treatment of advanced prostatic carcinoma. South Med J 1977 Dec;70(12):1411-3 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/594790.
  2. 2.0 2.1 Aro J, Haapiainen R, Kajanti M, Rannikko S, Alfthan O. Comparison of endocrine and radiation therapy in locally advanced prostatic cancer. Eur Urol 1988;15(3-4):182-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3063541.
  3. 3.0 3.1 Aro J, Haapiainen R, Kajanti M, Rannikko S, Alfthan O. Orchiectomy, estrogen therapy and radiotherapy in locally advanced (T3-4 M0) prostatic cancer. Scand J Urol Nephrol Suppl 1988;110:103-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3187397.
  4. 4.0 4.1 Johansson JE, Andersson SO, Holmberg L, Bergström R. Primary orchiectomy versus estrogen therapy in advanced prostatic cancer--a randomized study: results after 7 to 10 years of followup. J Urol 1991 Mar;145(3):519-22; discussion 522-3 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1997702.
  5. 5.0 5.1 5.2 Boccardo F, Pace M, Rubagotti A, Guarneri D, Decensi A, Oneto F, et al. Goserelin acetate with or without flutamide in the treatment of patients with locally advanced or metastatic prostate cancer. The Italian Prostatic Cancer Project (PONCAP) Study Group. Eur J Cancer 1993;29A(8):1088-93 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8518017.
  6. 6.0 6.1 6.2 6.3 Prostate Cancer Trialists' Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet 2000 Apr 29;355(9214):1491-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10801170.
  7. 7.0 7.1 Tyrrell CJ, Altwein JE, Klippel F, Jurincic-Winkler C, Varenhorst E, Lunglmayr G, et al. Comparison of an LH-RH analogue (Goeserelin acetate, 'Zoladex') with combined androgen blockade in advanced prostate cancer: final survival results of an international multicentre randomized-trial. International Prostate Cancer Study Group. Eur Urol 2000 Feb;37(2):205-11 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10705200.
  8. Boccardo F, Barichello M, Battaglia M, Carmignani G, Comeri G, et al. Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer: updated results of a multicentric trial. The Italian Prostatic Cancer Project (PONCAP) Study Group. Eur Urol 2002 Nov;42(5):481-90 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12429158.
  9. Iversen P, Tyrrell CJ, Kaisary AV, Anderson JB, Van Poppel H, Tammela TL, et al. Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of followup. J Urol 2000 Nov;164(5):1579-82 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11025708.
  10. Schröder FH, Kurth KH, Fosså SD, Hoekstra W, Karthaus PP, et al. Early versus delayed endocrine treatment of pN1-3 M0 prostate cancer without local treatment of the primary tumor: results of European Organisation for the Research and Treatment of Cancer 30846--a phase III study. J Urol 2004 Sep;172(3):923-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15310999.
  11. Studer UE, Whelan P, Albrecht W, Casselman J, de Reijke T, Hauri D, et al. Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891. J Clin Oncol 2006 Apr 20;24(12):1868-76 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16622261.

Back to top

Appendices