Effects of joint risk-stratified screening for ovarian cancer with transvaginal ultrasound and CA125
Principal Investigator
Name
Yubei Huang
Degrees
M.D., Ph.D
Institution
Tianjin Medical University Cancer Institute and Hospital
Position Title
Research Associate
Email
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
PLCO-1107
Initial CDAS Request Approval
Nov 22, 2022
Title
Effects of joint risk-stratified screening for ovarian cancer with transvaginal ultrasound and CA125
Summary
Ovarian cancer (OC) is the ninth common cancer and the seventh leading cause of cancer death in women worldwide. Screening for OC with serum cancer antigen 125 (CA125), transvaginal ultrasound (TVU), or a combination of both, is expected to promote early stage shift and ultimately reduce OC mortality.
However, the updated randomized controlled trials (RCTs) and systematic reviews have also concluded that OC screening in average-risk and asymptomatic women does not support a reduction in OC mortality. The lack of a significant increase in the proportion of early OC, the decrease in the proportion of late OC, the lower positive predictive value of screening due to low-incidence OC, and the dilution effect including clinically diagnosed OC at the end of screening may all contribute to the absence of a significant reduction in OC mortality. Until now, there is no more appropriate image screening modality to replace OC screening at TVU. Therefore, considering that the null cutoff value of CA125 used in current screening practice is considered to be the leading and direct cause of the non-significant reduction in OC mortality, there is a need to redefine the reference level of population-based CA125 screening. Although several metrics and algorithms based on CA125 variability have been developed, they are not well utilized in the general population due to their complexity. Although CA125 changes are highly correlated with baseline CA125, CA125 increments, and the time interval between consecutive CA125 tests, however, no studies have explored and compared different CA125 progression metrics constructed based on these factors.
Therefore, in this study, based on parallel screening for CA125 and TVU in prostate, lung, colorectal, and ovarian cancer (PLCO) screening trials, we aimed to identify population-based CA125 reference values for OC screening, explore the best subgroup-specific CA125 progression indicators and their corresponding optimal cut-point values, and furthermore, after integrating TVU and CA125 cut-point values, different joint risk stratification screening strategies were proposed and evaluated.
However, the updated randomized controlled trials (RCTs) and systematic reviews have also concluded that OC screening in average-risk and asymptomatic women does not support a reduction in OC mortality. The lack of a significant increase in the proportion of early OC, the decrease in the proportion of late OC, the lower positive predictive value of screening due to low-incidence OC, and the dilution effect including clinically diagnosed OC at the end of screening may all contribute to the absence of a significant reduction in OC mortality. Until now, there is no more appropriate image screening modality to replace OC screening at TVU. Therefore, considering that the null cutoff value of CA125 used in current screening practice is considered to be the leading and direct cause of the non-significant reduction in OC mortality, there is a need to redefine the reference level of population-based CA125 screening. Although several metrics and algorithms based on CA125 variability have been developed, they are not well utilized in the general population due to their complexity. Although CA125 changes are highly correlated with baseline CA125, CA125 increments, and the time interval between consecutive CA125 tests, however, no studies have explored and compared different CA125 progression metrics constructed based on these factors.
Therefore, in this study, based on parallel screening for CA125 and TVU in prostate, lung, colorectal, and ovarian cancer (PLCO) screening trials, we aimed to identify population-based CA125 reference values for OC screening, explore the best subgroup-specific CA125 progression indicators and their corresponding optimal cut-point values, and furthermore, after integrating TVU and CA125 cut-point values, different joint risk stratification screening strategies were proposed and evaluated.
Aims
(1) To explore the population-based CA125 reference levels for OC screening.
(2) To explore the optimal CA125 progression indicators and their cut-point values.
(3) To propose and evaluate a combined risk stratification screening strategy integrating TVU, CA125 screening and CA125 progression cut-point values.
Collaborators
Yubei, Huang, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China