Abstract
BackgroundThe prognostic role of serum alkaline phosphatase (ALP) has been found in several kinds of solid malignant tumor, but has never been extensively discussed in pancreatic cancer, especially through the application of dynamic survival model which incorporates the varying nature of ALP measurements.MethodsWe conducted a retrospective study which successfully collected 551 histopathologically confirmed pancreatic ductal adenocarcinoma (PDAC) patients from a cancer specialized hospital in southwest China. The association between variant ALP which measured during the whole survival period and the overall survival (OS) of PDAC patients was evaluated by using dynamic Anderson-Gill (AG) model. Exhaustive sensitivity analysis was performed by adopting continuous cut-offs of ALP.ResultsAfter adjusted for possible confounding of serum albumin, total bilirubin and leukocyte counts, AG model revealed that, serum ALP during the survival period was nonlinearly associated with the OS of PDAC: for resected patients, compared with those whose ALP results ranged within the first quartile (<P25), patients whose ALP measurements belonged to the second (P25-P50), the third (P50-P75), and the forth (>P75) quartiles were observed 1.14 (95% CI: 0.29–4.56), 3.93 (95% CI: 1.23–12.60), 3.87 (95% CI: 1.32–11.36) folds of death hazard; whereas in un-resected PDAC patients, the hazard ratios (HRs) were 1.15 (95% CI: 0.79–1.68), 1.92 (95% CI: 1.32–2.78), and 1.97 (95% CI: 1.30–2.98), respectively. Sensitivity analysis revealed that, for both resected and un-resected patients, the results of AG model were robust with regard to various cut-offs of ALP, and an increased ALP was in general associated with significantly increased hazard of death.ConclusionSerum ALP during the survival period was significantly associated with the OS of PDAC patients, especially for resected early stage PDAC patients. Future studies with expanded sample size and refined prospective design should be implemented to corroborate our major findings. Besides, the underlying mechanism for this possible hazardous role of ALP should also be investigated.
Highlights
The prognostic role of serum alkaline phosphatase (ALP) has been found in several kinds of solid malignant tumor, but has never been extensively discussed in pancreatic cancer, especially through the application of dynamic survival model which incorporates the varying nature of ALP measurements
During the whole survival period, ALP measurements of Pancreatic cancer (PC) patients will inevitably vary from test to test, dynamic survival models which can further adjust for this time-varying nature of ALP should be used to generate a more credible conclusion
While both multivariate Cox proportional hazards model and AG model revealed insignificant linear association between every 20 units increase of serum ALP and overall survival (OS), the elevation of dynamic serum ALP was in general associated with deteriorated OS of pancreatic ductal adenocarcinoma (PDAC): in resected patients, compared with the patients whose ALP results ranged within the first quartile (P75) quartiles were observed 1.14, 3.93, 3.87 folds of death hazard; whereas in un-resected PDAC patients, the hazard ratios (HRs) were 1.15, 1.92, and 1.97, respectively (Fig. 1)
Summary
The prognostic role of serum alkaline phosphatase (ALP) has been found in several kinds of solid malignant tumor, but has never been extensively discussed in pancreatic cancer, especially through the application of dynamic survival model which incorporates the varying nature of ALP measurements. The median survival length for all diagnosed PC patients is 3–6 months, and the 5-year survival rate is generally less than 5% [6,7,8,9]. Under this circumstance, an expanded search on indicators which are of prognostic interest of PC is necessary and imperative. During the whole survival period, ALP measurements of PC patients will inevitably vary from test to test, dynamic survival models which can further adjust for this time-varying nature of ALP should be used to generate a more credible conclusion
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