Asymptomatic pancreatic cystic neoplasms: maximizing survival and quality of life using Markov-based clinical nomograms

Abstract

Background & aims: The natural history and management of pancreatic cysts, especially for branch duct intraductal papillary mucinous neoplasms (BD-IPMNs), remain uncertain. We developed evidence-based nomograms to assist with clinical decision making.

Methods: We used decision analysis with Markov modeling to compare competing management strategies in a patient with a pancreatic head cyst radiographically suggestive of BD-IPMN, including the following: (1) initial pancreaticoduodenectomy (PD), (2) yearly noninvasive radiographic surveillance, (3) yearly invasive surveillance with endoscopic ultrasound, and (4) "do nothing." We derived probability estimates from a systematic literature review. The primary outcomes were overall and quality-adjusted survival. We depicted the results in a series of nomograms accounting for age, comorbidities, and cyst size.

Results: Initial PD was the dominant strategy to maximize overall survival for any cyst greater than 2 cm, regardless of age or comorbidities. In contrast, surveillance was the dominant strategy for any lesion less than 1 cm. However, when measuring quality-adjusted survival, the do-nothing approach maximized quality of life for all cysts less than 3 cm in patients younger than age 75. Once age exceeded 85 years, noninvasive surveillance dominated. Initial PD did not maximize quality of life in any age group or cyst size.

Conclusions: Management of pancreatic cysts can be guided using novel Markov-based clinical nomograms, and depends on age, cyst size, comorbidities, and whether patients value overall survival vs quality-adjusted survival. For patients focused on overall survival, regardless of quality of life, surgery is optimal for lesions greater than 2 cm. For patients focused on quality-adjusted survival, a 3-cm threshold is more appropriate for surgery except for the extreme elderly.

Figure 1

Example Markov State Diagram. Patients in the model cycled between health states according to annual probability estimates. The model included a wide variety of possible movements across the competing strategies. As an example, the diagram below demonstrates the possible state paths for patients undergoing non-invasive surveillance in a patient with an underlying, unrecognized, malignant IPMN.

Figure 2

Clinical Nomograms to Guide Decision-Making in a Hypothetical 65-Year-Old Patient with Suspected BD-IPMN (Figure 2a) and a Hypothetical 85-Year-Old Patient with Suspected BD-IPMN (Figure 2b). Panel A. Nomogram for a patient focused primarily on maximizing overall survival, independent of quality of life. Panel B. Nomogram for a patient focused on maximizing quality-adjusted survival. Figure 2a. For example, for a 65 year old patient with a 2cm cyst and an estimated 5% risk of perioperative mortality from a Whipple operation, surgery maximizes overall survival, yet doing nothing maximizes quality-adjusted survival. However, if the cyst exceeds 3cm in size, then surgery is warranted in both instances (see text for details). Figure 2b.For example, for an 85 year old patient with a 2cm cyst and an estimated 8% risk of perioperative mortality from a Whipple operation, surgery maximizes overall survival, yet doing nothing maximizes quality-adjusted survival. However, if perioperative mortality exceeded 13%, then surgery would never be warranted for this patient (see text for details).

Figure 2

Clinical Nomograms to Guide Decision-Making in a Hypothetical 65-Year-Old Patient with Suspected BD-IPMN (Figure 2a) and a Hypothetical 85-Year-Old Patient with Suspected BD-IPMN (Figure 2b). Panel A. Nomogram for a patient focused primarily on maximizing overall survival, independent of quality of life. Panel B. Nomogram for a patient focused on maximizing quality-adjusted survival. Figure 2a. For example, for a 65 year old patient with a 2cm cyst and an estimated 5% risk of perioperative mortality from a Whipple operation, surgery maximizes overall survival, yet doing nothing maximizes quality-adjusted survival. However, if the cyst exceeds 3cm in size, then surgery is warranted in both instances (see text for details). Figure 2b.For example, for an 85 year old patient with a 2cm cyst and an estimated 8% risk of perioperative mortality from a Whipple operation, surgery maximizes overall survival, yet doing nothing maximizes quality-adjusted survival. However, if perioperative mortality exceeded 13%, then surgery would never be warranted for this patient (see text for details).