DOI: 10.25934/pr00009845
title: Serum sodium maintenance levels and outcomes in patients with advanced prostate cancer

description: The project background: Sodium is an important mineral that helps balance the amount of fluid (water) in your body. It also helps your nerves and muscles to work properly. Hyponatremia refers to low serum levels, serum is the clear, protein-rich liquid portion of blood. Symptoms of hyponatremia can include nausea and vomiting, loss of energy and confusion. Serious hyponatremia can cause seizures, coma and even death.

Electrolytes are minerals that give off an electrical charge when they dissolve in fluids like blood and urine, which the body makes but also gets from foods, drinks and supplements. Hyponatremia is the most common electrolyte disorder in patients with cancer and there is evidence that it negatively affects the course of the disease. Many studies have demonstrated that in different cancer types, both progression-free survival (the time from initial treatment until disease worsening) and overall survival (the length of time from the date of diagnosis or start of treatment, that patients diagnosed with the disease are still alive) are negatively affected by hyponatremia, whereas the correction of serum sodium (amount of sodium in your blood) has a positive effect on patient outcome. 
Previous studies have found that lower sodium levels were associated with shorter overall survival and progression-free survival and lower disease control rate, which is the rate of patients with complete response, partial response, or stable disease due to their therapy, compared with sodium levels greater than or equal to 140 mmol/L. Data also demonstrated that hyponatremia is independently associated with a worse outcome. Additionally, alterations in normal dietary intake due to tumor metastasis may impact blood sodium levels.
In other cancer types, such as lung cancer and liver cancer, researchers have also demonstrated an association between low serum sodium levels and poorer patient prognosis. However, the relationship between serum sodium and patient prognosis in prostate cancer remains unclear. 

Therefore, we aim to investigate the association between serum sodium levels and prognosis in prostate cancer using large-scale, high-quality clinical trials with complete follow-up data. By regularly monitoring serum electrolyte levels in these trials, we will explore the correlation between maintaining serum sodium levels throughout the course of the disease and patient outcomes.
Necessity of the research and how it will add to medical science or patient care: This study will utilize three large cohorts: ARASENS, ARAMIS, FIRSTANA. The findings of the aims described above can provide valuable guidance to clinicians for improved long-term management of patients' disease progression and facilitate the convenient identification of those with poorer prognoses.
The research may affect all the patients with advanced prostate cancer.

How the research will be conducted: We will perform a post-hoc analysis using patient level data from the ARASENS (Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)), ARAMIS (Nonmetastatic castration-resistant prostate cancer (nmCRPC)), and FIRSTANA (Metastatic castration-resistant prostate cancer (mCRPC)) trials. Specifically, we will focus on patients with comprehensive follow-up data on serum sodium levels and analyze them separately based on their initial treatment. 
The outcomes of interest in our study include:
overall survival 
radiologic progression-free survival or tumor progression-free survival- the time from treatment initiation until disease progression or worsening on CT and/or Tc bone scan (a similar scan but using a nuclear tracing agent) per trial definition. It is worth noting that radiologic progression-free survival or tumor progression-free survival is not applicable in the ARASENS study. Therefore, the study exclusively investigate OS in ARASENS.
What design and methods you have you chosen and why (in brief): In each arm of every clinical trial, we will calculate the average serum sodium concentration from the time of enrollment and initiation of treatment until reaching the study endpoint. Patients will be divided into two groups based on their serum sodium levels: high serum sodium maintenance levels (≥140mmol/L) and low serum sodium maintenance levels (<140mmol/L). We will assess the independent correlation between serum sodium concentration and prognosis. All analyses will be conducted in RStudio (A programming language for statistical computing and graphics).