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Colorectal

Colorectal Parallel Session

27: Evaluation of Pathologic Complete Response as a Surrogate Endpoint in Rectal Cancer Clinical Trials: A Systematic Review and Meta-Analysis

Friday, March 22, 2024
11:32am – 11:42am ET
Location: C101
Disclosure(s):
Kavin Sugumar, MD: No financial relationships to disclose
Jessica J. Lie, MD MPH: No financial relationships to disclose
Introduction: The FDA approved the use of pathologic complete response (pCR) as a surrogate endpoint for long-term outcomes in 2012. Since then, its utilization in clinical trials has increased significantly given pCR’s benefit of being an objective short-term outcome with associated cost-savings. However, recent studies have reported inconsistency in correlating pCR with survival outcomes. This meta-analysis aimed to evaluate the correlation between pCR and survival outcomes in randomized controlled trials (RCTs) of rectal cancer.


Methods: We queried various databases for abstracts and full-text articles published from database inception through January 2021. RCTs evaluating neoadjuvant therapies in rectal cancer that reported pCR, overall survival (OS), and disease-free survival (DFS) were included. Weighted linear regression was used to study the correlation between pCR, OS and DFS. Odds ratios of pCR and hazard ratios for OS and DFS were used for the meta-regression analysis.


Results: A total of 14 RCTs met inclusion criteria and were included, contributing a total of 8,380 patients. The included RCTs had an overall low risk of bias and high certainty of evidence. There was no significant publication bias based on funnel plot analysis (Egger’s test p=0.56). On meta-regression analysis, pCR was not correlated with OS (β coefficient 0.63, 95% CI -0.56 - 1.81, p=0.27, Figure). Similarly, pCR was not correlated with DFS (β coefficient -1.08, 95% CI -2.87 - 0.70; p=0.21). Consistent results were confirmed in a sensitivity analysis excluding 2 studies that had relatively higher contribution to data variation based on Baujat influence plot analysis.


Conclusions: This systematic review and meta-analysis of 14 RCTs found that pCR was not correlated with OS and DFS in interventional trials of patients with rectal cancer. These findings suggest caution should be exercised when using pCR as a surrogate primary endpoint in regulatory neoadjuvant trials of rectal cancer.

Learning Objectives:

  • Upon completion, participant will be able to describe the correlation between pathologic complete response and overall survival.
  • Upon completion, participant will be able to describe the correlation between pathologic complete response and disease free survival.
  • Upon completion, participant will be able to determine if pathologic complete response is an appropriate surrogate endpoint to utilize when designing rectal cancer trials.