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. 2025 Mar;30(3):539-550.
doi: 10.1007/s10147-024-02676-z. Epub 2024 Dec 10.

Characterization of PSA dynamics and oncological outcomes in patients with metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors

Yasutaka Yamada  1 , Kodai Sato  1 , Shinichi Sakamoto  2 , Takuya Tsujino  3 , Sinpei Saito  1 , Kazuki Nishimura  3 , Tatsuo Fukushima  3 , Ko Nakamura  3 , Yuki Yoshikawa  3 , Tomohisa Matsunaga  3 , Ryoichi Maenosono  3 , Manato Kanesaka  1 , Takayuki Arai  1 , Tomokazu Sazuka  1 , Yusuke Imamura  1 , Kazumasa Komura  3 , Kazuo Mikami  4 , Kazuyoshi Nakamura  5 , Satoshi Fukasawa  6 , Kazuto Chiba  7 , Yukio Naya  8 , Maki Nagata  9 , Atsushi Komaru  10 , Hiroomi Nakatsu  11 , Haruhito Azuma  3 , Tomohiko Ichikawa  1
Affiliations

Characterization of PSA dynamics and oncological outcomes in patients with metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors

Yasutaka Yamada et al. Int J Clin Oncol. 2025 Mar.

Abstract

Background: This study investigated the characteristics of prostate-specific antigen (PSA) dynamics when androgen receptor signaling inhibitor (ARSI), or vintage agent (bicalutamide) was used for patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Patients and methods: A total of 213 mHSPC patients from each of the ARSI and bicalutamide groups treated between 2015 and 2022 were selected from multiple institutions using propensity score-matched analysis to align backgrounds. PSA progression-free survival (PFS) and overall survival (OS) were assessed. PSA level at 3 months, PSA nadir level, and time to PSA nadir were examined to analyze of PSA kinetics.

Results: ARSI treatment significantly improved PSA PFS compared to bicalutamide (P = 0.0063), although no significant difference in OS was seen (P = 0.3134). No significant differences were observed between treatment groups in median PSA levels at 3 months (1.47 vs 0.52 ng/ml, P = 0.3042) or PSA nadir levels (0.263 vs 0.1345 ng/ml, P = 0.1228). Bicalutamide treatment demonstrated longer time to nadir than ARSI in progression-free cases (median: 243 vs 213.5 days, P = 0.0003). Survival tree analysis found that PSA nadir ≤ 1.5 ng/ml and time to nadir ≥ 145 days were the optimal cut-offs for best stratifying OS with bicalutamide, while PSA nadir ≤ 0.45 ng/ml and time to nadir ≥ 70 days were optimal with ARSI.

Conclusion: No significant differences in PSA response was seen between groups; however, distinct optimal cut-offs were demonstrated for PSA nadir and time to nadir. The present findings will be useful for optimal PSA monitoring for mHSPC patients and for early identification of poor-prognosis populations.

Keywords: Androgen receptor signaling inhibitor; Bicalutamide; Metastatic hormone-sensitive prostate cancer; PSA dynamics; PSA nadir; Time to PSA nadir.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no conflict of interest. Ethical approval: The protocol for this research project has been approved by a suitably constituted ethics committee of the institution, and it conforms to the provisions of the Declaration of Helsinki. This study was approved by the Institutional Review Board of Chiba University Hospital (M10238) and Osaka Medical and Pharmaceutical University Hospital (RIN750-2571).

Figures

Fig. 1
Fig. 1
Comparison of survival between ARSI and Vintage treatment. A PSA PFS, B OS
Fig. 2
Fig. 2
Methodology of survival tree analysis
Fig. 3
Fig. 3
Survival analysis divided by optimal cut-off PSA nadir level. A Vintage treatment group. B ARSI treatment group
Fig. 4
Fig. 4
Survival analysis divided by optimal cut-off for time to PSA nadir. A Vintage treatment group. B ARSI treatment group
Fig. 5
Fig. 5
Survival analysis by risk classification using PSA nadir and time to PSA nadir. A Vintage treatment group. B ARSI treatment group
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References

    1. Siegel RL, Giaquinto AN, Jemal A (2024) Cancer statistics, 2024. CA Cancer J Clin 74(1):12–49. 10.3322/caac.21820 - PubMed
    1. Yamada Y, Beltran H (2021) The treatment landscape of metastatic prostate cancer. Cancer Lett 519:20–29. 10.1016/j.canlet.2021.06.010 - PMC - PubMed
    1. Davis ID, Martin AJ, Stockler MR et al (2019) Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med 381(2):121–131. 10.1056/NEJMoa1903835 - PubMed
    1. Smith MR, Hussain M, Saad F et al (2022) Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med 386(12):1132–1142. 10.1056/NEJMoa2119115 - PMC - PubMed
    1. de Bono JS, Logothetis CJ, Molina A et al (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364(21):1995–2005. 10.1056/NEJMoa1014618 - PMC - PubMed

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