In this study, we identified the prevalence of high Scr in patients with terminal cancer in an acute palliative care unit. We also confirmed that Scr, sex, performance status, WBC count, and AST were strongly associated with the survival of patients in end-of-life.
Previous studies have noted that high Scr is a significant prognostic factor in patients with various types and stages of cancer; high preoperative Scr in renal cell carcinoma is associated with impaired 5-year cancer-specific survival ; high Scr in ovarian cancer is related to age at first diagnosis and predicts poor prognosis ; high Scr is an independent predictor of lower overall survival in colorectal cancer patients , and independent risk factors in vulvar cancer patients . Therefore, we hypothesized that the survival time of cancer patients in end-of-life can be associated with Scr, which was investigated in this study.
There are several explanations for the relationship between Scr and remaining life expectancy of patients with terminal cancer. The major contributor for high Scr in patients with cancer may be decreased renal function. Usually, Cr, urea, and uric acid levels are estimated to evaluate the extent of renal dysfunction. Among them, Scr is the most widely used blood test value that indicates renal function . Cr, a low-molecular-weight protein, is metabolized by non-enzymatic phosphorylation in muscle cells at a constant rate and is mainly eliminated through the kidney . It is filtered through the glomerulus and excreted from the proximal tubules. Renal impairment is common in patients with cancer owing to cancer itself, multiple organ failure, and postoperative complications or chemotoxicity [30–32].
In addition, Cr metabolism is linked to cancer progression and metastasis through several mechanisms. Cr is the end product of creatine and creatine phosphate metabolism and is utilized as an essential energy source . Creatine is transported into the muscle and phosphorylated by creatine kinase (CK). Previous studies have shown that CK is upregulated during cancer progression . As cancer cells use creatine as a readily available energy source, the end product of creatine increases . Thus, high Scr in patients with terminal cancer is related to the state of cancer progression and is considered a prognostic factor.
We found that the prevalence of high Scr was approximately 27%, and the median survival time of high Scr group was 12 days. Although increased Scr has been reported in patients with terminal cancer as death approaches, there has been limited data on the prevalence of high Scr in these groups [35, 36]. A multi-center study of terminally ill cancer patients in Korea demonstrated that 11.0% of patients had high Scr, but with different cut-off values (≥ 1.5 mg/dL) .
Medical judgement on active dying is important in palliative care. A minimum of 2 weeks preparation is required for patients and their caregivers to face a dignified death. During this period, the palliative care team must provide specific preparations for their last moments as well as physical, mental, and spiritual comfort. In Korea, the standard for judging whether the ‘Hospice, Palliative Care, and Life-sustaining Treatment Decision-making Act’ is enforced is based on the physician’s medical judgment on the last days of life . From this point of view, a median survival time of 12 days in patients with high Scr has a special meaning; Cr, a relatively cost-effective and simple blood test value, can be helpful in medically identifying active dying without additional unnecessary inconveniences.
Consistent with previous findings, leukocytosis and high AST levels were associated with the survival time of patients with cancer in end-of-life [5, 7, 24]. Leukocytosis was related to the general condition of the patient and inflammation, and abnormal liver function tests are related to liver metastases, infections, direct effects of tumors, and chemotherapeutic drugs. Therefore, leukocytosis and high AST levels are related to poor prognosis, reflecting the poor general condition of patients with terminal cancer.
This study has several limitations. First, some confounders, such as body mass index (BMI) could not be analyzed because of the retrospective design. In general, the weight and height of patients in palliative care units are rarely measured because of their poor condition or the unnecessary discomfort it can cause them. In addition, a study of patients with terminal cancer revealed that BMI did not significantly influence their survival time, and measured body weight may not be accurate owing to the presence of ascites or lymphedema . Second, we did not exclude patients with renal cancer or chronic kidney disease, which might strongly affect Scr levels. Furthermore, this was a single-center study that cannot represent general patients with cancer in end of life. Therefore, a multi-center, larger study is required.
Nonetheless, we confirmed an association between relatively simple blood test parameters and survival time in a palliative care setting, particularly regarding the usefulness of Scr. Further studies are warranted to explore the validity and reliability of Scr as an independent prognostic factor.