Competing Risks for Mortality in Patients With Asymptomatic Pancreatic Cystic Neoplasms: Implications for Clinical Management.

Abstract

Pancreatic cystic neoplasms (PCNs) are being detected with increased frequency. Current clinical practice guidelines emphasize management based on cyst-related features. We aimed to evaluate the impact of comorbidity on mortality in PCN patients via competing risk analysis. We analyzed a retrospective cohort of patients diagnosed between 2005-2010, with follow-up through 2015, for overall and cause-specific mortality. Comorbidities were classified by the Charlson comorbidity index. We used Cox proportional hazards regression to evaluate the independent effect of cyst features, age, gender, and comorbidities on cause-specific mortality. Subgroup analysis was performed to determine the cause-specific mortality based on four a priori clinical profiles-healthy patients with low- or high-risk cysts, and high-comorbidity patients with low- or high-risk cysts. A total of 1,800 patients with PCNs comprised the study cohort (median follow-up 5.7 years). A total of 402 deaths (22.3%) occurred during the study period: 43 pancreatic cancer and 359 non-pancreatic cancer deaths. Compared to healthy patients without any high-risk cyst features (reference group), patients with high comorbidity as well as high-risk cyst features had an increased risk of overall mortality (Cox hazard ratio 6.30, 95% confidence interval (CI) 4.71, 8.42, P<0.01), pancreatic cancer mortality (subdistribution hazard ratio (SHR) 51.13, 95% CI 6.35, 411.29, P<0.01), as well as non-pancreatic cancer mortality (SHR 5.24, 95% CI 3.85, 7.12, P<0.01). Meanwhile, low-risk patients with a high-risk cyst were more likely to experience pancreatic cancer mortality (SHR 68.14, 95% CI 9.27, 501.01, P<0.01) rather than non-pancreatic cancer mortality (SHR 1.22, 95% CI 0.88, 1.71, P=0.23), compared to the reference group. Similarly, compared to the reference group, high-risk patients with a low-risk cyst were more likely to experience non-pancreatic cancer mortality (SHR 3.96, 95% CI 2.98, 5.26, P<0.01) rather than pancreatic cancer mortality (SHR 2.35, 95% CI 0.14, 38.82, P=0.55). Most of the deaths in the study were unrelated to pancreatic cancer. This has implications for clinical management. By applying patient-related factors in conjunction with cyst features, we defined commonly encountered patient profiles to help guide PCN clinical management.