Cancer biomarkers are at the leading edge of Precision Medicine, and offer both tremendous opportunities and
challenges. In particular, biomarker development to detect recurrence in cancer survivors is blossoming, as
surveillance testing with serial biomarker measurements offers an opportunity to detect recurrence at a point
when treatment may be curative. However, frequent biomarker testing may cause more harm than benefit for
low-risk individuals, due to the costs and complications of unnecessary testing and increased likelihood of false
positives leading to unnecessary treatment. Unfortunately, tailoring surveillance to individual patients is a
complex decision-making problem that requires understanding the heterogeneity in biomarker measurements
across patients and across time within patients. As a result, surveillance testing guidelines using one-size-fits-
all strategies continue to be common in most cancers, despite their uncertain clinical utility. The overarching
goal of the proposed research is to develop a decision-making framework to identify optimal surveillance
strategies among cancer survivors. The specific aims are: Aim 1. Develop and evaluate a sequential decision-
making framework by merging statistical methods for prediction modeling with economics concepts for value of
information (VOI) analysis to guide individualized decisions about testing and treatment for recurrence using
serial biomarker testing, with the goal of optimizing long-term patient outcomes. This aim will build on
preliminary work and develop a dynamic decision-making algorithm that uses accumulated information at a
given time to update predictions and guide decisions. The broad applicability of the framework will be
demonstrated by considering three distinct cancer surveillance settings: colorectal cancer (CRC), prostate
cancer (PrCA), and chronic myeloid leukemia (CML), which capture a range of decision-making problems in
cancer surveillance. Aim 2. Apply this framework to existing electronic health record (EHR) and cohort study
data to identify a risk-adaptive surveillance strategy for detecting CRC recurrence that targets high-risk patients
for frequent follow-up and treatment, and recommends less frequent follow-up for low-risk patients. Aim 3.
Assess the comparative effectiveness of the proposed risk-adaptive surveillance strategy versus guideline-
based surveillance in CRC. Aim 4. Use existing data to evaluate the generalizability of the framework by
addressing the optimal frequency of follow-up among (a) low-risk men with recurrent PrCA, for whom treatment
may be safely delayed for a prolonged period, and (b) long-term survivors of CML, who achieve long-term
remission but currently continue to be monitored frequently. We address a significant problem in cancer
survivorship care using approaches to help resolve the uncertainty that clinicians and patients face when
confronted with using new and evolving biomarker technologies to monitor for recurrence after patients have
survived their primary cancer.
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