Elevated Levels of Serum Thymidine Kinase 1 Predict Poor Survival for Patients with Metastatic Prostate Cancer

Teemu J Murtola; Aino Siltari; Paavo Raittinen; Teuvo L J Tammela; Stig Linder; Anita Csizmarik; Gero Kramer; Tibor Szarvas

doi:10.1016/j.euros.2024.10.010

Elevated Levels of Serum Thymidine Kinase 1 Predict Poor Survival for Patients with Metastatic Prostate Cancer

Eur Urol Open Sci. 2024 Oct 25:70:135-141. doi: 10.1016/j.euros.2024.10.010. eCollection 2024 Dec.

Authors

Teemu J Murtola^{1

2}, Aino Siltari^{1

3}, Paavo Raittinen⁴, Teuvo L J Tammela^{1

2}, Stig Linder^{5

6}, Anita Csizmarik⁷, Gero Kramer⁸, Tibor Szarvas^{7

9}

Affiliations

¹ Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
² Department of Urology, TAYS Cancer Center, Tampere, Finland.
³ Department of Pharmacology, University of Helsinki, Helsinki, Finland.
⁴ Department of Mathematics and Systems Analysis, Aalto University, Helsinki, Finland.
⁵ Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
⁶ Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
⁷ Department of Urology, Semmelweis University, Budapest, Hungary.
⁸ Department of Urology, Medical University of Vienna, Vienna, Austria.
⁹ Department of Urology, University of Duisburg-Essen, Essen, Germany.

Abstract

Background and objective: Prostate-specific antigen (PSA) is of limited value as a surrogate marker for overall survival (OS) in prostate cancer (PC). Serum thymidine kinase 1 (sTK1) is an enzyme expressed by actively dividing cells. Our aim was to evaluate the value of sTK1 as prognostic biomarker in metastatic hormone-sensitive PC (mHSPC) and metastatic castration-resistant PC (mCRPC).

Methods: sTK1 was examined in three cohorts: (1) 43 men with de novo mHSPC managed with androgen deprivation monotherapy; (2) 99 patients with mCRPC managed with androgen receptor signaling inhibitors (ARSIs); and (3) 98 patients with mCRPC treated with docetaxel. sTK1 levels were determined at treatment initiation. OS was evaluated using Cox regression analysis.

Key findings and limitations: In the mHSPC cohort, sTK1 levels in the highest quartile were associated with OS (hazard ratio [HR] 7.77, 95% confidence interval [CI] 2.25-26.9) in comparison to the lowest quartile after multivariable adjustment for age, Gleason score, and PSA. Similarly, sTKI was associated with poor OS in the mCRPC group treated with ARSIs (upper quartile: HR 5.22, 95% CI 2.23-12.2) after multivariable adjustment for age, PSA, and Eastern Cooperative Oncology Group performance status. In the docetaxel-treated mCRPC group the association between OS and sTK1 was lower but still significant (multivariable-adjusted HR 2.28, 95% CI 1.13-4.60). Limitations include the nonrandomized inclusion of patients for different treatments, which could lead to selection bias.

Conclusions and clinical implications: sTK1 predicted OS in mHSPC and mCRPC, demonstrating additional value over established clinical risk factors. sTK1 should be measured in randomized clinical trials of treatments for advanced PC to validate its predictive value.

Patient summary: We found that for patients with metastatic prostate cancer, high levels of a protein called TK1 that is involved in cell division was linked to higher risk of death. Our findings need to be confirmed in other studies.

Keywords: Antiandrogen; Docetaxel; Prostate cancer; Survival; Thymidine kinase 1; Treatment prediction.