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. 2019 Aug 19;9(1):12071.
doi: 10.1038/s41598-019-48600-8.

Prognostic significance of early changes in serum biomarker levels in patients with newly diagnosed metastatic prostate cancer

Shintaro Narita  1   2 , Kyoko Nomura  3 , Shingo Hatakeyama  4   5 , Masahiro Takahashi  6   5 , Toshihiko Sakurai  7   5 , Sadafumi Kawamura  8   5 , Senji Hoshi  9   5 , Masanori Ishida  10   5 , Toshiaki Kawaguchi  11   5 , Shigeto Ishidoya  12   5 , Jiro Shimoda  10   5 , Hiromi Sato  13   5 , Koji Mitsuzuka  6   5 , Tatsuo Tochigi  8   5 , Norihiko Tsuchiya  7   5 , Chikara Ohyama  4   5 , Yoichi Arai  6   5 , Kengo Nagashima  14 , Tomonori Habuchi  13   5
Affiliations

Prognostic significance of early changes in serum biomarker levels in patients with newly diagnosed metastatic prostate cancer

Shintaro Narita et al. Sci Rep. .

Abstract

We evaluated the impact of early changes in serum biomarker levels on the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who were initially treated with androgen deprivation therapy (ADT). We retrospectively investigated 330 patients with mHSPC whose serum maker levels were at baseline and at 2-4 months. An optimal Cox regression model was established with the highest optimism-corrected concordance index based on 10-fold cross-validation. The median cancer-specific survival (CSS) and overall survival (OS) were 7.08 and 6.47 years (median follow-up, 2.53 years), respectively. In the final optimal Cox model with serum biomarker levels treated as time-varying covariates, prostate-specific antigen (PSA), hemoglobin (Hb), and alkaline phosphatase (ALP) significantly increased the risk of poor survival in the context of both CSS and OS. Kaplan-Meier curves stratified by the three risk factors of high PSA, low Hb and high ALP desmondtated that median OS were not reached with none of these factors, 6.47 years with one or two factors, and 1.76 years with all three factors.Early changes in serum biomarker levels after ADT may be good prognostic markers for the survival of patients with mHSPC.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Kaplan–Meier curves for CSS in patients with mHSPC who were initially treated with ADT. CSS stratified by PSA (a), ALP (b), and Hb (c) at 2–4 months, respectively. The p values were computed using a log-rank test.
Figure 2
Figure 2
Kaplan–Meier curves for OS in patients with mHSPC who were initially treated with ADT. OS stratified by PSA (a), ALP (b), and Hb (c) at 2–4 months, respectively. The p values were computed using a log-rank test.
Figure 3
Figure 3
Kaplan–Meier curves for CSS (a) and OS (b) in patients with mHSPC who were initially treated with ADT according to the risk classification based on the presence of high serum levels of PSA and ALP at 2–4 months and a low serum level of Hb at 2–4 months. The risk groups were formed based on the combination of these three factors, as follows: zero risk factors, one or two risk factors, and three risk factors, respectively. The p values were computed using a log-rank test.
Figure 4
Figure 4
Scheme of patient selection. A consecutive group of 629 adult patients diagnosed with mHSPC between March 2008 and May 2016 was retrospectively identified at each institute. We first excluded 24 patients due to missing data regarding survival outcome and then excluded 275 patients due to missing data for variables required for the analyses. The remaining 330 patients were used as the study subjects for our analyses.
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