Purpose: The aim of our retrospective study was to determine the time to progression to castration-resistant prostate cancer (CRPC) in prostate cancer patients who undergo combined androgen blockade (CAB), as well as their prognoses.
Materials and methods: We examined the overall survival (OS) and disease-specific survival rates, as well as the time to CRPC development, in 387 patients who were treated with CAB for prostate cancer. The disease-specific survival rate and time to CRPC were stratified by prostate-specific antigen (PSA) levels, Gleason score (GS), and presence of metastasis at diagnosis. We designated high-risk patients as those satisfying at least two of the following three criteria: extent of disease of bone metastasis grade ≥2, presence of metastasis at diagnosis, and a GS ≥8.
Results: The 10- and 15-year OS rates were 74.0% and 50.4%, respectively, while the corresponding disease-specific survival rates were both 86.8%. Metastasis at diagnosis was an independent prognostic factor for disease-specific survival. The median time to CRPC development was 140.7 months. A PSA level ≥20 ng/mL, a GS ≥8, and the presence of metastasis at diagnosis were independent predictors of a shorter time to CRPC development. The 10-year disease-specific survival rate in the high-risk group was significantly lower than that in the low-risk group (approximately 74% vs. 98%), and the time to CRPC development was significantly shorter (median: 20.5 months vs. not reached).
Conclusions: The time to CRPC development was shorter in high-risk prostate cancer patients with metastases. Such patients require alternative novel treatment modalities.
Keywords: castration-resistant prostate cancer; combined androgen blockade; hormone-sensitive prostate cancer; progression; survival.
Conflict of interest statement
CONFLICTS OF INTEREST T. Iguchi and T. Nakatani have received research funding from Astellas Japan (Tokyo, Japan), Bayer Yakuhin. Ltd (Osaka, Japan). The remaining authors have declared no conflict of interest.
Prostate-specific antigen response to deferred combined androgen blockade therapy using bicalutamide predicts survival after subsequent oestrogen and docetaxel therapies in patients with castration-resistant prostate cancer.BJU Int. 2012 Oct;110(8):1149-55. doi: 10.1111/j.1464-410X.2012.10959.x. Epub 2012 Feb 28. BJU Int. 2012. PMID: 22369348
EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer.Eur Urol. 2014 Feb;65(2):467-79. doi: 10.1016/j.eururo.2013.11.002. Epub 2013 Nov 12. Eur Urol. 2014. PMID: 24321502 Review.
Effectiveness of Deferred Combined Androgen Blockade Therapy Predicts Efficacy in Abiraterone Acetate Treated Metastatic Castration-Resistant Prostate Cancer Patients after Docetaxel.Front Pharmacol. 2017 Nov 22;8:836. doi: 10.3389/fphar.2017.00836. eCollection 2017. Front Pharmacol. 2017. PMID: 29213237 Free PMC article.
Clinical outcomes and prognostic factors in patients with newly diagnosed metastatic prostate cancer initially treated with androgen deprivation therapy: a retrospective multicenter study in Japan.Int J Clin Oncol. 2020 Jan 9. doi: 10.1007/s10147-019-01614-8. Online ahead of print. Int J Clin Oncol. 2020. PMID: 31919691
Time-to-event Outcomes in Men with Nonmetastatic Castrate-resistant Prostate Cancer-A Systematic Literature Review and Pooling of Individual Participant Data.Eur Urol Focus. 2019 Sep;5(5):788-798. doi: 10.1016/j.euf.2018.03.010. Epub 2018 Apr 4. Eur Urol Focus. 2019. PMID: 29627197 Review.
Cited by 1 article
Comparative prognostic implication of treatment response assessments in mCRPC: PERCIST 1.0, RECIST 1.1, and PSA response criteria.Theranostics. 2020 Feb 10;10(7):3254-3262. doi: 10.7150/thno.39838. eCollection 2020. Theranostics. 2020. PMID: 32194866 Free PMC article.
- Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1941;1:293–97. - PubMed
- Labrie F, Dupont A, Belanger A, Cusan L, Lacourciere Y, Monfette G, Laberge JG, Emond JP, Fazekas AT, Raynaud JP, Husson JM. New hormonal therapy in prostatic carcinoma: combined treatment with an LHRH agonist and an antiandrogen. Clin Invest Med. 1982;5:267–75. - PubMed
- Prostate Cancer Trialists Collaborative Group Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Prostate Cancer Trialists’ Collaborative Group. Lancet. 2000;355:1491–98. - PubMed
- Akaza H, Yamaguchi A, Matsuda T, Igawa M, Kumon H, Soeda A, Arai Y, Usami M, Naito S, Kanetake H, Ohashi Y. Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients. Jpn J Clin Oncol. 2004;34:20–28. - PubMed
- Akaza H, Hinotsu S, Usami M, Arai Y, Kanetake H, Naito S, Hirao Y, Study Group for the Combined Androgen Blockade Therapy of Prostate Cancer Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer. 2009;115:3437–45. - PubMed