|1R01CA258352-01A1 Interpret this number
|University Of Washington
|Comparative-Effectiveness of Pretreatment Lung Cancer Nodal Staging
Our goal is to reduce diagnostic and treatment errors, improve survival, and increase the value of care for lung
cancer patients by improving our ability to select patients who benefit from a pretreatment lymph node biopsy.
Accurately determining whether cancer has spread to lymph nodes and the extent of spread (a process called
nodal staging) is critical for appropriate treatment selection. Understaging can lead to omission of
chemotherapy or unnecessary surgery. Overstaging can lead to unnecessary chemotherapy and omission of
surgery. Diagnostic and treatment errors negatively impact survival. These errors commonly occur when using
imaging alone for nodal staging. A biopsy can reduce the chances of error, but it can also result in rare, life-
threatening adverse events. Each biopsy costs ~$5,000. Practice guidelines recommend selectively performing
a biopsy when imaging findings suggest nodal disease. However, national biopsy rates are less than half of
what they should be. Moreover, there is 25-fold facility-level variability not explained by access to care, case-
mix, or clinician or facility characteristics. These findings, along with the low levels of evidence underlying
guideline recommendations, suggest true clinical and scientific uncertainty over the indications for lymph node
biopsy. We conducted a pilot study to better understand how well guideline recommendations select patients
for biopsy and learned that guideline-concordant nodal staging selects all patients with true nodal disease for
biopsy and two-thirds of patients without true nodal disease for biopsy. Additionally, we developed and
validated an alternative risk-based nodal staging strategy that uses a prediction model to stratify and select
patients for lymph node biopsy. Preliminary data show that it identifies nearly all patients with true nodal
disease for biopsy but selects fewer patients without nodal true nodal disease for biopsy. However, the
relationship between selection strategies for lymph node biopsy and patient outcomes remains unknown. We
hypothesize that guideline-concordant nodal staging is associated with higher 5-year survival rates compared
with guideline-discordant nodal staging (Aim I) and that risk-based nodal staging is equivalent to guideline-
concordant nodal staging in terms of survival but superior in terms of lower biopsy-related adverse events and
healthcare expenditures (Aim II). Testing these hypotheses will require ~4,000 patients; therefore, a trial is not
feasible at this time. We will create a novel cohort of lung cancer patients using the Cancer Research Network
infrastructure to conduct Aim I using an observational, comparative-effectiveness study design with advanced
regression techniques and machine learning to minimize confounding. Additionally, we will use patient-level
data from this cohort as model inputs in a comparative-effectiveness simulation model that we will develop to
conduct Aim II. Findings from this study will lead to: 1) developing and testing implementation strategies
designed to increase guideline-concordant nodal staging, 2) alternative guideline recommendations for nodal
staging, and/or 3) justifying trials comparing outcomes between different nodal staging strategies.
Acquiring tissue for advanced lung cancer diagnosis and comprehensive biomarker testing: A National Lung Cancer Roundtable best-practice guide.
, Nishino M.
, Osarogiagbon R.U.
, Rivera M.P.
, Rosenthal L.S.
, Smith R.A.
, Farjah F.
, Sholl L.M.
, Silvestri G.A.
, Johnson B.E.
CA: a cancer journal for clinicians, 2023 Jul-Aug; 73(4), p. 358-375.