Low Alanine Aminotransferase, as a Marker of Sarcopenia and Frailty, Is Associated with Shorter Survival Among Prostate Cancer Patients and Survivors. A Retrospective Cohort Analysis of 4064 Patients

Abstract

Background: Sarcopenia is characterized by loss of muscle mass and function and is associated with frailty, a syndrome with higher likelihood of falls, fractures, physical disability, and mortality. Both frailty and sarcopenia are known markers of shorter survival in various cancer patient populations. Low alanine aminotransferase (ALT), reflecting loss of muscle mass (sarcopenia), may be associated with greater frailty and shorter survival in multiple cancers.

Objective: To assess the potential association between low ALT and shorter survival among prostate cancer (PCa) patients and survivors.

Design setting and participants: This was a retrospective analysis of a historical cohort of PCa patients and survivors. Patients were defined as those still actively receiving PCa treatment, while those no longer receiving such treatment were classified as PCa survivors.

Outcome measurements and statistical analysis: ALT data were obtained from results for basic biochemical blood testing carried out for patients on their first hospital admission. Patients were divided into two groups: those with ALT ≥17 IU/l and those with ALT <17 IU/l. Univariate and multivariable analyses were conducted for between-group survival comparisons.

Results and limitations: We identified 9489 PCa records. The final study cohort with ALT data available included 4064 patients with ALT <40 IU/l. Of this cohort, 536 patients were actively receiving medical anticancer therapy for PCa. The mean age for the entire cohort was 74.6 yr (standard deviation 9.6) and the median ALT level was 19.28 IU/l; 1676 patients (41%) had low ALT (<17 IU/l). On univariate analysis, low ALT was associated with a 78% increase in mortality risk (95% confidence interval [CI] 1.62-1.97; p < 0.001). A sensitivity analysis of the 536 patients actively receiving medical anticancer treatment revealed that low ALT was associated with a 48% increase in mortality risk (95% CI 1.19-1.85; p = 0.001). In a multivariable model controlled for age, kidney disease, history of cerebrovascular event/transient ischemic attack, and baseline prostate-specific antigen, low ALT was still associated with a 35% increase in mortality risk (95% CI 1.12-1.63; p = 0.001). Limitations include the single-center, retrospective design.

Conclusions: Low ALT, which is indicative of sarcopenia and frailty, is associated with shorter survival among PCa patients and survivors and could potentially be used for treatment personalization.

Patient summary: We compared survival for prostate cancer patients and survivors according to their blood level of the protein alanine aminotransferase (ALT). Low ALT levels in the general population are associated with loss of muscle mass. We found that in our group of prostate cancer patients and survivors, the risk of death from any cause was higher for those with low ALT levels.

Keywords: Alanine aminotransferase; Frailty; Prostate cancer; Prostate-specific antigen; Sarcopenia; Survival.

Fig. 1

Consolidated Standards of Reporting Trials (CONSORT) diagram of patient inclusion in the study.

Fig. 2

Kaplan Meir survival analysis according to alanine aminotransferase (ALT) level (<17 IU/l vs ≥17 IU/l).

Fig. 3

Sensitivity analysis for patients actively receiving medical anticancer treatment. Kaplan Meir survival by alanine aminotransferase (ALT) level (<17 IU/l vs ≥17 IU/l).