Overdiagnosis and alternative endpoints in cancer screening trials (OVERCAST)
Principal Investigator
Name
Hilary Robbins
Degrees
PhD MHS MSPH
Institution
International Agency for Research on Cancer (IARC)
Position Title
Scientist
Email
About this CDAS Project
Study
NLST
(Learn more about this study)
Project ID
NLST-1383
Initial CDAS Request Approval
Jan 27, 2025
Title
Overdiagnosis and alternative endpoints in cancer screening trials (OVERCAST)
Summary
The OVERCAST project will address two central, contemporary issues in cancer screening: i) overdiagnosis and ii) which endpoints are used to evaluate screening benefit. The overarching strategy of OVERCAST is to bring together data from many different randomized clinical trials (RCTs) of cancer screening to learn more than was previously possible by analyzing trials one-by-one. We have demonstrated the power of this approach in two prior publications, which each serve as the basis for one aim.
Aim 1 builds on a prior study which quantified how estimates of overdiagnosis in low-dose CT lung cancer screening are influenced by post-screening follow-up time on (Li et al, Int J Ca 2022). In OVERCAST, we will extend this work to breast, colorectal, prostate, and ovarian cancers to estimate the long-term percentage of cancers that are overdiagnosed via screening. This approach has the potential to reduce the controversy around overdiagnosis by showing that results from different trials may be more similar than is apparent, and can be interpreted coherently as a whole.
Aim 2 also builds on prior work, published in JAMA, comparing stage and mortality endpoints to quantify the benefit of cancer screening (Feng et al, JAMA 2024). In OVERCAST, we will extend this work to describe how the endpoints of cancer mortality and late-stage cancer incidence change over extended follow-up time in RCTs. This work is important to quantify the extent to which late-stage incidence can be used as a suitable alternative for cancer mortality when evaluating novel technologies such as multi-cancer early detection (MCED) tests.
Aim 1 builds on a prior study which quantified how estimates of overdiagnosis in low-dose CT lung cancer screening are influenced by post-screening follow-up time on (Li et al, Int J Ca 2022). In OVERCAST, we will extend this work to breast, colorectal, prostate, and ovarian cancers to estimate the long-term percentage of cancers that are overdiagnosed via screening. This approach has the potential to reduce the controversy around overdiagnosis by showing that results from different trials may be more similar than is apparent, and can be interpreted coherently as a whole.
Aim 2 also builds on prior work, published in JAMA, comparing stage and mortality endpoints to quantify the benefit of cancer screening (Feng et al, JAMA 2024). In OVERCAST, we will extend this work to describe how the endpoints of cancer mortality and late-stage cancer incidence change over extended follow-up time in RCTs. This work is important to quantify the extent to which late-stage incidence can be used as a suitable alternative for cancer mortality when evaluating novel technologies such as multi-cancer early detection (MCED) tests.
Aims
1. Estimate the long-term percentage of cancers which are overdiagnosed by cancer screening, evaluating how this metric changes over extended follow-up time
2. Assess and quantify alternative endpoints for cancer screening trials which could feasibly be used in place of cancer mortality
Collaborators
Ryan Langdon, International Agency for Research on Cancer
Xiaoshaung Feng, International Agency for Research on Cancer
Mattias Johansson, International Agency for Research on Cancer
Ruth Etzioni, Fred Hutchinson Cancer Research Center