Association Between the Pretreatment Albumin-to-Alkaline Phosphatase Ratio and Clinical Outcomes in Patients With Bladder Cancer Treated With Radical Cystectomy: A Retrospective Cohort Study

Abstract

Objective: Serum albumin-to-alkaline phosphatase ratio (AAPR) has been proven to be a prognostic indicator of many malignant tumors. However, whether it can predict the prognosis of bladder cancer (BC) patients who underwent radical cystectomy (RC) remains unclear. This study was designed to assess the relationship between AAPR and clinical outcomes in patients with BC treated with RC.

Methods: The clinicopathological data of 199 BC patients receiving RC in our institution from January 2012 to December 2017 were retrospectively collected and analyzed. They were divided into three groups based on the optimal cut-off values and the association between AAPR groups and their clinical outcomes were evaluated.

Results: The average age of the patients was (64.0 ± 8.7) years and 79.9% were male. Based on the cut-off values of AAPR, patients were divided into three groups: low-AAPR group (AAPR < 0.37, n = 35), medium-AAPR group (AAPR = 0.37-0.59, n = 61) and high-AAPR group (AAPR > 0.59, n = 103). The median overall survival (OS) of each AAPR group was 12.5, 24, and 29 months, respectively (P value <0.0001). After adjusting the Cox proportional hazards model, medium- and high- AAPR groups showed a reduced risk trend of death, with a risk ratio of 0.44 (95% CI = 0.21-0.91) and 0.25 (95% CI = 0.12-0.49), respectively (P for trend <0.001). No nonlinear relationship was identified by smooth fitting curve between AAPR and OS. By subgroup analysis, we observed that compared to the low-AAPR group, the trends of the HRs in the medium- and high-AAPR group were decreased across nearly all subgroups after stratification. Moreover, the AAPR-based nomograms for OS, CSS and RFS were also constructed. The C-index showed a good predictive accuracy (OS, C-index 0.728, 95% CI 0.663-0.793; CSS, C-index 0.792, 95% CI 0.748-0.838; RFS, C-index 0.784, 95% CI 0.739-0.829).

Conclusion: Pretreatment AAPR is significantly associated with the prognosis of BC patients receiving RC, which can be conducive to the clinical decision-making and risk stratification in those patients. The nomogram based on AAPR is a reliable model for predicting survival of BC patients after RC.

Keywords: albumin-to-alkaline phosphatase ratio; bladder cancer; nomogram; prognostic impact; radical cystectomy.

Figure 1

The patient selection flowchart.

Figure 2

X-tile analyses of OS based on patient data to determine the optimal cut-off values for AAPR (A) and age (B). The optimal cut-off values are shown in histograms of the entire cohort. OS, overall survival; AAPR, albumin-to-alkaline phosphatase ratio.

Figure 3

The adjusted smooth fitting curve between pretreatment AAPR and OS of BC patients based on two-piece-wise regression model. A linear relationship between AAPR and OS was observed. The red solid line and blue dashed line represent the estimated values and their corresponding 95% confidence intervals. OS, overall survival; AAPR, albumin-to-alkaline phosphatase ratio; BC, bladder cancer.

Figure 4

Kaplan-Meier curves of OS (A), CSS (B) and RFS (C) in BC patients stratified by AAPR. OS, overall survival; CSS, cancer-specific survival; RFS, recurrence-free survival; BC, bladder cancer; AAPR, albumin-to-alkaline phosphatase ratio.

Figure 5

Forest plot for presenting the association between the hazard ratio of overall survival and medium- (A) and high-AAPR (B) in BC patients. AAPR, albumin-to-alkaline phosphatase ratio; BC, bladder cancer.

Figure 6

Nomogram model constructed by independent prognostic factors predicting 3- and 5-year OS for BC patients treated with RC (A); the ROC curve of AAPR and AAPR-based nomogram for predicting OS in the primary cohort (B); corresponding calibration curves of nomogram model for 3- and 5- year OS (C, D). OS, overall survival; AAPR, albumin-to-alkaline phosphatase ratio; BC, bladder cancer; ROC, receiver operating characteristic; AUC, area under curve; CI, confidence interval.

Figure 7

Nomogram model constructed by independent prognostic factors predicting 3- and 5-year CSS for BC patients treated with RC (A); the ROC curve of AAPR and AAPR-based nomogram for predicting CSS in the primary cohort (B); corresponding calibration curves of nomogram model for 3- and 5- year CSS (C, D). CSS, cancer-specific survival; AAPR, albumin-to-alkaline phosphatase ratio; BC, bladder cancer; ROC, receiver operating characteristic; AUC, area under curve; CI, confidence interval.

Figure 8

Nomogram model constructed by independent prognostic factors predicting 3- and 5-year RFS for BC patients treated with RC (A); the ROC curve of AAPR and AAPR-based nomogram for predicting RFS in the primary cohort (B); corresponding calibration curves of nomogram model for 3- and 5- year RFS (C, D). RFS, recurrence-free survival; AAPR, albumin-to-alkaline phosphatase ratio; BC, bladder cancer; ROC, receiver operating characteristic; AUC, area under curve; CI, confidence interval.