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24.09.2019 | Urology - Original Paper

Predictors of poor response to first-generation anti-androgens as criteria for alternate treatments for patients with non-metastatic castration-resistant prostate cancer

verfasst von: Kenichiro Fukuoka, Jun Teishima, Hirotaka Nagamatsu, Shogo Inoue, Tetsutaro Hayashi, Koji Mita, Masanobu Shigeta, Kanao Kobayashi, Mitsuru Kajiwara, Yuichi Kadonishi, Takatoshi Tacho, Akio Matsubara

Erschienen in: International Urology and Nephrology

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Abstract

Purpose

There are no criteria for administering first- or second-generation anti-androgens (FGA and SGA, respectively) to patients with non-metastatic castration-resistant prostate cancer (nmCRPC). This study aimed to assess the efficacy of alternative FGA therapy in nmCRPC patients and the prognosis of these patients and to identify factors for predicting patients potentially responsive to FGA.

Methods

Data from 63 men with nmCRPC who underwent alternative FGA therapy (bicalutamide, flutamide, or chlormadinone acetate) as first-line therapy after failure of primary androgen-deprivation therapy (PADT) between 2004 and 2017 at Hiroshima University Hospital and affiliated hospitals were retrospectively investigated. The associations of clinicopathological parameters with overall survival (OS) and prostate-specific antigen (PSA) progression-free survival (PFS) of alternative FGA-treated patients were analyzed.

Results

Time to CRPC [p = 0.007, hazard ratio (HR) = 4.77], regional lymph node involvement at the diagnosis of CRPC (p = 0.022, HR = 2.42), and PSA-PFS of alternative FGA therapy ≤ 6 months (p = 0.020, HR = 2.39) were identified as prognostic factors using a multivariate analysis. Additionally, Cox proportional hazard models revealed that PSA nadir value > 1 ng/mL during PADT (p = 0.034, HR = 2.40) and time from starting PADT to PSA nadir ≤ 1 year (p = 0.047, HR = 1.85) were predictive factors for worse PSA-PFS in alternative FGA therapy.

Conclusions

Shorter time to CRPC, regional lymph node involvement, PSA nadir during PADT > 1 ng/mL, and time from starting PADT to PSA nadir ≤ 1 year might suggest the potential benefit of immediate commencement of SGA, compared to FGA administration after nmCRPC diagnosis.

Akaza H, Usami M, Hinotsu S et al (2004) Characteristics of patients with prostate cancer who have initially been treated by hormone therapy in Japan: J-CaP surveillance. Jpn J Clin Oncol 34:329–336CrossRef

Hussain M, Fizazi K, Saad F et al (2018) Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med 378:2465–2474CrossRef

Smith MR, Saad F, Chowdhury S et al (2018) Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 378:1408–1418CrossRef

Mizokami A, Kadono Y, Kitagawa Y et al (2017) Therapies for castration-resistant prostate cancer in a new era: the indication of vintage hormonal therapy, chemotherapy and the new medicines. Int J Urol 24:566–572CrossRef

European Association of Urology (EAU). Oncology Guidelines: Prostate Cancer, 2018. https://uroweb.org/guideline/prostate-cancer/. Accessed 24 May 2019

American Urological Association (AUA). Clinical guidelines: Castration-resistant prostate cancer (2018) https://www.auanet.org/guidelines/prostate-cancer-castration-resistant-guideline. Accessed 24 May 2019

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®): Prostate Cancer. Version 2. 2019–April 17, 2019. https://www.nccn.org/professionals/physician_gls/default.aspx. Accessed 24 May 2019

Miyake H, Matsushita Y, Watanabe H et al (2019) Comparative assessment of prognostic outcomes between first-generation antiandrogens and novel androgen-receptor-axis-targeted agents in patients with non-metastatic castration-resistant prostate cancer. Int J Clin Oncol. https://doi.org/10.1007/s10147-019-01412-2 CrossRefPubMed

Penson DF, Armstrong AJ, Concepcion R et al (2016) Enzalutamide versus bicalutamide in castration-resistant prostate cancer: the STRIVE Trial. J Clin Oncol 34:2098–2106CrossRef

10.

Iguchi T, Tamada S, Kato M et al (2019) Enzalutamide versus flutamide for castration-resistant prostate cancer after combined androgen blockade therapy with bicalutamide: study protocol for a multicenter randomized phase II trial (the OCUU-CRPC study). BMC Cancer 19:339CrossRef

11.

Mori K, Kimura T, Ito K et al (2018) Earlier use of androgen receptor-axis-targeted drugs may improve overall survival in patients with non-metastatic castration-resistant prostate cancer. Prostate 78:766–772CrossRef

12.

Suzuki H, Okihara K, Miyake H et al (2008) Alternative nonsteroidal antiandrogen therapy for advanced prostate cancer that relapsed after initial maximum androgen blockade. J Urol 180:921–927CrossRef

13.

Fujikawa K, Matsui Y, Fukuzawa S et al (2000) Prostate-specific antigen levels and clinical response to flutamide as the second hormone therapy for hormone-refractory prostate carcinoma. Eur Urol 37:218–222CrossRef

14.

Miyake H, Hara I, Eto H (2005) Clinical outcome of maximum androgen blockade using flutamide as second-line hormonal therapy for hormone-refractory prostate cancer. BJU Int 96:791–795CrossRef

15.

Okihara K, Ukimura O, Kanemitsu N et al (2007) Clinical efficacy of alternative antiandrogen therapy in Japanese men with relapsed prostate cancer after first-line hormonal therapy. Int J Urol 14:128–132CrossRef

16.

Nishimura K, Arichi N, Tokugawa S et al (2007) Effects of flutamide as a second-line agent for maximum androgen blockade of hormone refractory prostate cancer. Int J Urol 14:264–267CrossRef

17.

Yasui M, Uemura K, Yoneyama S et al (2016) Predictors of poor response to secondary alternative antiandrogen therapy with flutamide in metastatic castration-resistant prostate cancer. Jpn J Clin Oncol 46:1042–1046CrossRef

18.

Akaza H, Hinotsu S, Usami M et al (2009) Combined androgen blockade with bicalutamide for advanced prostate cancer. Cancer 115:3437–3445CrossRef

19.

Kwak C, Jeong SJ, Park MS et al (2002) Prognostic significance of the nadir prostate specific antigen level after hormone therapy for prostate cancer. J Urol 168:995–1000CrossRef

20.

Altwein JE, Schmidt A (2002) Prostate-specific antigen dynamics predict risk of progression in advanced prostate cancer treated with bicalutamide plus castration. Urol Int 68:220–225CrossRef

21.

Benaim EA, Pace CM, Lam PM et al (2002) Nadir prostate-specific antigen as a predictor of progression to androgen-independent prostate cancer. Urology 59:73–78CrossRef

22.

Morote J, Trilla E, Esquena S et al (2004) Nadir prostate-specific antigen best predicts the progression to androgen-independent prostate cancer. Int J Cancer 108:877–881CrossRef

23.

Park SC, Rim JS, Choi HY et al (2009) Failing to achieve a nadir prostate-specific antigen after combined androgen blockade: predictive factors. Int J Urol 16:670–675CrossRef

24.

Sim HG, Lau WK, Cheng CW et al (2004) Predictors of androgen independence in metastatic prostate cancer. BJU Int 93:1221–1224CrossRef

25.

Teoh JY, Tsu JH, Yuen SK et al (2017) Survival outcomes of Chinese metastatic prostate cancer patients following primary androgen deprivation therapy in relation to prostate-specific antigen nadir level. Asia Pac J Clin Oncol 13:e65–e71CrossRef

26.

Tomioka A, Tanaka N, Yoshikawa M et al (2014) Nadir PSA level and time to nadir PSA are prognostic factors in patients with metastatic prostate cancer. BMC Urol 14:33CrossRef

27.

Sasaki T, Ohnishi T, Hoshina A (2011) Nadir PSA level and time to PSA nadir following primary androgen deprivation therapy are the early survival predictors for prostate cancer patients with bone metastasis. Prostate Cancer Prostatic Dis 14:248–252CrossRef

28.

Huang SP, Bao BY, Wu MT et al (2011) Impact of prostate-specific antigen (PSA) nadir and time to PSA nadir on disease progression in prostate cancer treated with androgen-deprivation therapy. Prostate 71:1189–1197CrossRef

29.

Hamano I, Hatakeyama S, Narita S et al (2019) Impact of nadir PSA level and time to nadir during initial androgen deprivation therapy on prognosis in patients with metastatic castration-resistant prostate cancer. World J Urol. https://doi.org/10.1007/s00345-019-02664-3 CrossRefPubMed

30.

Teoh JY, Tsu JH, Yuen SK et al (2015) Prognostic significance of time to prostate-specific antigen (PSA) nadir and its relationship to survival beyond time to PSA nadir for prostate cancer patients with bone metastases after primary androgen deprivation therapy. Ann Surg Oncol 22:1385–1391CrossRef

31.

Teoh JY, Tsu JH, Yuen SK et al (2017) Association of time to prostate-specific antigen nadir and logarithm of prostate-specific antigen velocity after progression in metastatic prostate cancer with prior primary androgen deprivation therapy. Asian J Androl 19:98–102PubMed

32.

Choueiri TK, Xie W, D’Amico AV et al (2009) Time to prostate-specific antigen nadir independently predicts overall survival in patients who have metastatic hormone-sensitive prostate cancer treated with androgen-deprivation therapy. Cancer 115:981–987CrossRef

Titel: Predictors of poor response to first-generation anti-androgens as criteria for alternate treatments for patients with non-metastatic castration-resistant prostate cancer
verfasst von: Kenichiro Fukuoka
Jun Teishima
Hirotaka Nagamatsu
Shogo Inoue
Tetsutaro Hayashi
Koji Mita
Masanobu Shigeta
Kanao Kobayashi
Mitsuru Kajiwara
Yuichi Kadonishi
Takatoshi Tacho
Akio Matsubara
Publikationsdatum: 24.09.2019
Verlag: Springer Netherlands
Erschienen in: International Urology and Nephrology
Print ISSN: 0301-1623
Elektronische ISSN: 1573-2584
DOI: https://doi.org/10.1007/s11255-019-02281-4

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