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Multicenter Study
. 2024 Jul 3;14(1):15307.
doi: 10.1038/s41598-024-65969-3.

PSA doubling time 4.65 months as an optimal cut-off of Japanese nonmetastatic castration-resistant prostate cancer

Shinichi Sakamoto  1 , Kodai Sato  2 , Takahiro Kimura  3 , Yoshiyuki Matsui  4 , Yusuke Shiraishi  5 , Kohei Hashimoto  6 , Hideaki Miyake  7 , Shintaro Narita  8 , Jun Miki  9 , Ryuji Matsumoto  10 , Takuma Kato  11 , Toshihiro Saito  12 , Ryotaro Tomida  13 , Masaki Shiota  14 , Akira Joraku  15 , Naoki Terada  16 , Shigetaka Suekane  17 , Tomoyuki Kaneko  18 , Shuichi Tatarano  19 , Yuko Yoshio  20 , Takayuki Yoshino  21 , Naotaka Nishiyama  22 , Eiryo Kawakami  23 , Tomohiko Ichikawa  2 , Hiroshi Kitamura  22
Affiliations
Multicenter Study

PSA doubling time 4.65 months as an optimal cut-off of Japanese nonmetastatic castration-resistant prostate cancer

Shinichi Sakamoto et al. Sci Rep. .

Abstract

A multicenter study of nonmetastatic castration-resistant prostate cancer (nmCRPC) was conducted to identify the optimal cut-off value of prostate-specific antigen (PSA) doubling time (PSADT) that correlated with the prognosis in Japanese nmCRPC. Of the 515 patients diagnosed and treated for nmCRPC at 25 participating Japanese Urological Oncology Group centers, 450 patients with complete clinical information were included. The prognostic values of clinical factors were evaluated with respect to prostate specific antigen progression-free (PFS), cancer-specific survival (CSS), and overall survival (OS). The optimal cutoff value of PSADT was identified using survival tree analysis by Python. The Median PSA and PSADT at diagnosis of nmCRPC were 3.3 ng/ml, and 5.2 months, respectively. Patients treated with novel hormonal therapy (NHT) showed significantly longer PFS (HR: hazard ratio 0.38, p < 0.0001) and PFS2 (HR 0.45, p < 0.0001) than those treated with vintage nonsteroidal antiandrogen agent (Vintage). The survival tree identified 4.65 months as the most prognostic PSADT cutoff point. Among the clinical and pathological factors PSADT of < 4.65 months remained an independent prognostic factor for OS (HR 2.96, p = 0.0003) and CSS (HR 3.66, p < 0.0001). Current data represented optimal cut-off of PSADT 4.65 months for a Japanese nmCRPC.

Keywords: NHT; PSA doubling time; Prostate cancer; Vintage; nmCRPC.

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Conflict of interest statement

Shinichi Sakamoto received honoraria from Janssen Inc. Shintaro Narita received honoraria from Janssen, and AstraZeneca Inc. Masaki Shiota received honoraria from Janssen, AstraZeneca, Astellas, Sanofi, and Bayer Inc. and research funding support from Daiichi Sankyo Inc. Takahiro Kimura received honoraria from Astellas, AstraZeneca, Bayer, Janssen, Sanofi, and Takeda Inc. Hiroshi Kitamura received honoraria from Astellas, AstraZeneca, Janssen, Sanofi, and Takeda Inc. and research grant from AstraZeneca Inc. Kohei Hashimoto received honoraria from Astellas, Janssen, Bayer and AstraZeneca Inc. Naoki Terada received honoraria from Janssen, Astellas and Bayer Inc. Hideaki Miyake received honoraria from Astellas, Bayer, Janssen, Sanofi, and Takeda Inc. Akira Joraku, Eiryo Kawakami, Jun Miki, Kodai Sato, Naotaka Nishiyama, Ryotaro Tomida, Ryuji Matsumoto, Shigetaka Suekane, Shuichi Tatarano, Takayuki Yoshino, Takuma Kato, Tomohiko Ichikawa, Tomoyuki Kaneko, Toshihiro Saito, Yoshiyuki Matsui, Yuko Yoshio, Yusuke Shiraishi have no conflict of interest to disclose.

Figures

Figure 1
Figure 1
Prognosis of nmCRPC patients. (A) Overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and time to second progression or death (PFS2) were analyzed by Kaplan–Meier method.
Figure 2
Figure 2
Prognostic comparison of nmCRPC patients treated by NHT and Vintage for whole cohort and propensity-score-matched pair cohort. The whole cohort of (A) overall survival (OS), (B) cancer-specific survival (CSS), (C) progression-free survival (PFS), and (D) time to second progression or death (PFS2) of nmCRPC patients treated with NHT and Vintage were analyzed using the Kaplan–Meier method. Propensity score-matched pair cohorts of (E) OS, (F) CSS, (G) PFS, and (H) PFS2 of nmCRPC patients treated with NHT and Vintage were analyzed using the Kaplan–Meier method. Statistical significance was evaluated using the log-rank test. The hazard risk (HR) was evaluated using a proportional hazard model.
Figure 3
Figure 3
Distribution of PSA doubling time (PSADT) and the time-dependent AUC of PSADT derived by survival forest. (A) Distribution of PSA doubling time (PSADT). (B) Percentage of PSADT ≤ 4.65 months and > 4.65 months. Time-dependent AUC of PSADT 4.65 months derived by survival tree and median PSADT 5.26 months for OS (C) and CSS (D). Time-dependent AUC of PSADT 2.85 months derived by survival tree and median PSADT 5.26 months for PFS and PFS2.
Figure 4
Figure 4
Prognostic significance of PSA doubling time (PSADT) cut-off derived by survival tree. (A) Overall survival (OS), and (B) cancer-specific survival (CSS) of nmCRPC patients with PSADT cut-offs of < 4.65 months and ≥ 4.65 months were analyzed by Kaplan–Meier method. (C) Progression-free survival (PFS) and (D) time to second progression or death (PFS2) of nmCRPC patients with PSADT cut-offs of < 2.85 months and ≥ 2.85 months were analyzed by Kaplan–Meier method. Statistical significance was evaluated by log-rank test. Hazard risk (HR) was evaluated by proportional hazard model.
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