Top

Published in:

Open Access 01-12-2021 | Prostate Cancer | Research article

Impact of pretreatment anemia on upfront abiraterone acetate therapy for metastatic hormone-sensitive prostate cancer: a multicenter retrospective study

Authors: Teppei Okamoto, Daisuke Noro, Shingo Hatakeyama, Shintaro Narita, Koji Mitsuzuka, Toshihiko Sakurai, Sadafumi Kawamura, Senji Hoshi, Jiro Shimoda, Toshikazu Tanaka, Toshiaki Kawaguchi, Shigeto Ishidoya, Akihiro Ito, Norihiko Tsuchiya, Tomonori Habuchi, Chikara Ohyama

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Anemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC.

Methods

We retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin < 13.0 g/dL, n = 20) and the non-anemia-ABI group (n = 46). The primary objective was to examine the impact of anemia on the progression-free survival (PFS; clinical progression or PC death before development of castration resistant PC) of patients in the upfront ABI group. Secondary objectives included an evaluation of the prognostic significance of upfront ABI and a comparison with a historical cohort (131 mHSPC patients with high tumor burden who received androgen deprivation therapy (ADT/complete androgen blockade [CAB] group) between 2014 and 2019).

Results

We found that the anemia-ABI group had a significantly shorter PFS than the non-anemia-ABI group. A multivariate Cox regression analysis showed that anemia was an independent prognostic factor of PFS in the upfront ABI group (hazard ratio, 4.66; P = 0.014). Patients in the non-anemia-ABI group were determined to have a significantly longer PFS than those in the non-anemia-ADT/CAB group (n = 68) (P < 0.001). However, no significant difference was observed in the PFS between patients in the anemia-ABI and the anemia-ADT/CAB groups (n = 63). Multivariate analyses showed that upfront ABI could significantly prolong the PFS of patients without anemia (hazard ratio, 0.17; P < 0.001), whereas ABI did not prolong the PFS of patients with anemia.

Conclusion

Pretreatment anemia was a prognostic factor among mHSPC patients who received upfront ABI. Although the upfront ABI significantly improved the PFS of mHSPC patients without anemia, its efficacy in patients with anemia might be limited.

Available only for authorised users

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29. https://doi.org/10.3322/caac.21254.CrossRefPubMed

Kimura T, Egawa S. Epidemiology of prostate cancer in Asian countries. Int J Urol. 2018;25(6):524–31. https://doi.org/10.1111/iju.13593.CrossRefPubMed

Fujimoto H, Nakanishi H, Miki T, Kubota Y, Takahashi S, Suzuki K, et al. Oncological outcomes of the prostate cancer patients registered in 2004: report from the Cancer registration committee of the JUA. Int J Urol. 2011;18(12):876–81. https://doi.org/10.1111/j.1442-2042.2011.02895.x.CrossRefPubMed

Okita K, Hatakeyama S, Narita S, Takahashi M, Sakurai T, Kawamura S, et al. The effect of treatment sequence on overall survival for men with metastatic castration-resistant prostate Cancer: a multicenter retrospective study. Clin Genitourin Cancer. 2020;18(2):e103–11. https://doi.org/10.1016/j.clgc.2019.09.006.CrossRefPubMed

Okamoto T, Hatakeyama S, Narita S, Takahashi M, Sakurai T, Kawamura S, et al. Impact of nutritional status on the prognosis of patients with metastatic hormone-naïve prostate cancer: a multicenter retrospective cohort study in Japan. World J Urol. 2018;0123456789(9):1827–35. https://doi.org/10.1007/s00345-018-2590-2.CrossRef

Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate Cancer. N Engl J Med. 2017;377(4):352–60. https://doi.org/10.1056/NEJMoa1704174.CrossRefPubMed

Suzuki H, Shin T, Fukasawa S, Hashine K, Kitani S, Ohtake N, et al. Efficacy and safety of abiraterone acetate plus prednisone in Japanese patients with newly diagnosed, metastatic hormone-naive prostate cancer: final subgroup analysis of LATITUDE, a randomized, double-blind, placebo-controlled, phase 3 study. Jpn J Clin Oncol. 2020;50(7):810–20. https://doi.org/10.1093/jjco/hyaa030.CrossRefPubMedPubMedCentral

Mori K, Janisch F, Mostafaei H, Lysenko I, Karakiewicz PI, Enikeev DV, et al. Prognostic value of hemoglobin in metastatic hormone-sensitive prostate Cancer: a systematic review and meta-analysis. Clin Genitourin Cancer. 2020;18(4):e402–9. https://doi.org/10.1016/j.clgc.2019.12.002.CrossRefPubMed

Sweeney CJ, Chen Y-H, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate Cancer. N Engl J Med. 2015;373(8):737–46. https://doi.org/10.1056/NEJMoa1503747.CrossRefPubMedPubMedCentral

10.

Okamoto T, Hatakeyama S, Narita S, Arai Y, Habuchi T, Ohyama C. Validation and development of the CHAARTED criteria in patients with hormone-naïve metastatic prostate cancer: a multi-institutional retrospective study in Japan. Int J Urol. 2020;27(1):90–1. https://doi.org/10.1111/iju.14136.CrossRefPubMed

11.

Sato H, Narita S, Tsuchiya N, Koizumi A, Nara T, Kanda S, et al. Impact of early changes in serum biomarkers following androgen deprivation therapy on clinical outcomes in metastatic hormone-sensitive prostate cancer. BMC Urol. 2018;18(1):32. https://doi.org/10.1186/s12894-018-0353-4.CrossRefPubMedPubMedCentral

12.

Nutritional anaemias. Report of a WHO scientific group. World Health Organ Tech Rep Ser. 1968;405:5–37 http://www.ncbi.nlm.nih.gov/pubmed/4975372. Accessed October 17, 2018.

13.

Yamamoto Y, Hosogaya S, Osawa S, Ichihara K, Onuma T, Saito A, et al. Nationwide multicenter study aimed at the establishment of common reference intervals for standardized clinical laboratory tests in Japan. Clin Chem Lab Med. 2013;51(8):1663–72. https://doi.org/10.1515/cclm-2012-0413.CrossRefPubMed

14.

Soloway MS, Hardeman SW, Hickey D, Todd B, Soloway S, Raymond J, et al. Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer. 1988;61(1):195–202 http://www.ncbi.nlm.nih.gov/pubmed/3334948. Accessed August 9, 2018, DOI: 10.1002/1097-0142(19880101)61:1<195::AID-CNCR2820610133>3.0.CO;2-Y.CrossRef

15.

Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the prostate Cancer clinical trials working group. J Clin Oncol. 2008;26(7):1148–59. https://doi.org/10.1200/JCO.2007.12.4487.CrossRefPubMedPubMedCentral

16.

Macciò A, Madeddu C, Gramignano G, et al. The role of inflammation, iron, and nutritional status in cancer-related anemia: results of a large, prospective, observational study. Haematologica. 2015;100(1):124–32. https://doi.org/10.3324/haematol.2014.112813.CrossRefPubMedPubMedCentral

17.

Beer TM, Tangen CM, Bland LB, Thompson IM, Crawford ED. Prognostic value of anemia in newly diagnosed metastatic prostate cancer: a multivariate analysis of southwest oncology group study 8894. J Urol. 2004;172(6 Pt 1):2213–7. http://www.ncbi.nlm.nih.gov/pubmed/15538234. Accessed October 17, 2018. https://doi.org/10.1097/01.ju.0000147771.92104.83.CrossRefPubMed

18.

Nalesnik JG, Mysliwiec AG, Canby-Hagino E. Anemia in men with advanced prostate cancer: incidence, etiology, and treatment. Rev Urol. 2004;6(1):1–4 http://www.ncbi.nlm.nih.gov/pubmed/16985564. Accessed August 31, 2020.PubMedPubMedCentral

19.

Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J. 2010;9(1):69. https://doi.org/10.1186/1475-2891-9-69.CrossRefPubMedPubMedCentral

20.

Shamdas GJ, Ahmann FR, Matzner MB, Ritchie JM. Leukoerythroblastic anemia in metastatic prostate cancer. Clinical and prognostic significance in patients with hormone-refractory disease. Cancer. 1993;71(11):3594–600. https://doi.org/10.1002/1097-0142(19930601)71:11<3594::aid-cncr2820711121>3.0.co;2-o.CrossRefPubMed

21.

Vaupel P, Thews O, Hoeckel M. Treatment resistance of solid tumors. Med Oncol. 2001;18(4):243–60. https://doi.org/10.1385/MO:18:4:243.CrossRefPubMed

22.

Dunst J. Low hemoglobin levels: influence on tumor biology and radiotherapy treatment outcome. Eur J Cancer Suppl. 2004;2(2):3–10. https://doi.org/10.1016/S1359-6349(03)00102-2.CrossRef

23.

Varlotto J, Stevenson MA. Anemia, tumor hypoxemia, and the cancer patient. Int J Radiat Oncol Biol Phys. 2005;63(1):25–36. https://doi.org/10.1016/j.ijrobp.2005.04.049.CrossRefPubMed

24.

Semenza G. Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol. 2002;64(5–6):993–8. https://doi.org/10.1016/s0006-2952(02)01168-1.CrossRefPubMed

25.

Fraga A, Ribeiro R, Príncipe P, Lopes C, Medeiros R. Hypoxia and prostate Cancer aggressiveness: a tale with many endings. Clin Genitourin Cancer. 2015;13(4):295–301. https://doi.org/10.1016/J.CLGC.2015.03.006.CrossRefPubMed

26.

Movsas B, Chapman JD, Hanlon AL, Horwitz EM, Greenberg RE, Stobbe C, et al. Hypoxic prostate/muscle po2 ratio predicts for biochemical failure in patients with prostate cancer: preliminary findings. Urology. 2002;60(4):634–9. https://doi.org/10.1016/S0090-4295(02)01858-7.CrossRefPubMed

27.

Ragnum HB, Vlatkovic L, Lie AK, Axcrona K, Julin CH, Frikstad KM, et al. The tumour hypoxia marker pimonidazole reflects a transcriptional programme associated with aggressive prostate cancer. Br J Cancer. 2015;112(2):382–90. https://doi.org/10.1038/bjc.2014.604.CrossRefPubMed

28.

O’Reilly D, Johnson P, Buchanan PJ. Hypoxia induced cancer stem cell enrichment promotes resistance to androgen deprivation therapy in prostate cancer. Steroids. 2019;152(January):108497. https://doi.org/10.1016/j.steroids.2019.108497.CrossRefPubMed

29.

Fearon K, Arends J, Baracos V. Understanding the mechanisms and treatment options in cancer cachexia. Nat Rev Clin Oncol. 2013;10(2):90–9. https://doi.org/10.1038/nrclinonc.2012.209.CrossRefPubMed

Title: Impact of pretreatment anemia on upfront abiraterone acetate therapy for metastatic hormone-sensitive prostate cancer: a multicenter retrospective study
Authors: Teppei Okamoto
Daisuke Noro
Shingo Hatakeyama
Shintaro Narita
Koji Mitsuzuka
Toshihiko Sakurai
Sadafumi Kawamura
Senji Hoshi
Jiro Shimoda
Toshikazu Tanaka
Toshiaki Kawaguchi
Shigeto Ishidoya
Akihiro Ito
Norihiko Tsuchiya
Tomonori Habuchi
Chikara Ohyama
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Prostate Cancer
Anemia
Prostate Cancer
Androgens
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08206-8

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

The value of complete blood count for the prognosis analysis of preoperative esophageal squamous cell carcinoma

The construction and validation of an RNA binding protein-related prognostic model for bladder cancer

Real-world study of the impact of recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) on quality of life and productivity in Europe

The impact of treatment facility type on the survival of brain metastases patients regardless of the primary cancer type

Bioinformatics analysis of C3 and CXCR4 demonstrates their potential as prognostic biomarkers in clear cell renal cell carcinoma (ccRCC)

The implementation of colorectal cancer screening interventions in low-and middle-income countries: a scoping review

Keynote webinar | Spotlight on antibody–drug conjugates in cancer