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

Shintaro Narita,Jiro Shimoda,Tatsuo Tochigi,Tomonori Habuchi,Sadafumi Kawamura,Yoichi Arai,Kyoko Nomura,Masahiro Takahashi,Shigeto Ishidoya,Norihiko Tsuchiya,Chikara Ohyama,Kengo Nagashima,Toshihiko Sakurai,Masanori Ishida,Toshiaki Kawaguchi,Koji Mitsuzuka,Hiromi Sato,Shingo Hatakeyama,Senji Hoshi

doi:10.1038/s41598-019-48600-8

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.

Highlights

Androgen deprivation therapy (ADT) is considered to be a mainstay of initial treatment for newly diagnosed metastatic hormone-sensitive prostate cancer
A combined androgen blockade was employed in 78.5% of the patients, whereas 21.5% were treated using LHRH antagonist
Patients in the high-risk group had significantly shorter median cancer-specific survival (CSS) and overall survival (OS) than those in the intermediate-risk group. These results indicate that the risk stratification depending on the three risk factors with serum levels of prostate-specific antigen (PSA), Hb, and alkaline phosphatase (ALP) at [2,3,4] months contributes to differences in the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC)

Summary

Introduction

Androgen deprivation therapy (ADT) is considered to be a mainstay of initial treatment for newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC). Previous studies have proposed several candidate biomarkers and risk stratification models for patients with mHSPC treated with ADT4,5. Recent studies have shown that dynamic changes in serum biomarker levels at the early “on therapy” period, including alterations in the levels of prostate-specific antigen (PSA) and alkaline phosphatase (ALP), are strong prognostic factors for clinical outcomes, including survival, in patients www.nature.com/scientificreports/. Www.nature.com/scientificreports with mHSPC and/or castration-resistant prostate cancer (CRPC)[6,7,8]. There is still less evidence regarding the impact of early changes in serum biomarker levels on clinical outcomes after ADT in recent diagnosed patients with mHSPC. This study aimed to investigate the prognostic impact of serum biomarker levels during early stages of ADT on the survival and develop a prognostic model for deployment among patients with newly diagnosed mHSPC

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Conclusion