TOPLINE:
According to a meta-analysis of randomized clinical trials (RCTs), pathologic complete response (pCR) was not associated with overall or disease-free survival in patients with rectal cancer, suggesting that the use of pCR as a surrogate endpoint for survival should be reexamined.
METHODOLOGY:
- Neoadjuvant trials in rectal cancer are increasingly using pCR as a surrogate endpoint for long-term outcomes, following recommendations by the FDA in 2012. However, while some research has shown an association between pCR and improved survival in rectal cancer on the patient level, consensus on the trial-level validity of pCR as a surrogate is lacking.
- Researchers conducted a systematic review and meta-analysis of 25 RCTs involving 11,882 patients with rectal cancer who underwent neoadjuvant therapies (mostly chemo radiation) followed by surgical resection.
- The researchers assessed the correlation between pCR and both overall survival and disease-free survival.
TAKEAWAY:
- Across trials that reported overall survival, weighted regression analysis revealed no correlation between pCR and overall survival (β, 0.37; 95% CI, -0.98 to 1.71; P = .57).
- Similarly, across trials reporting disease-free survival, there was no correlation between pCR and disease-free survival (β, -0.84; 95% CI, -2.55 to 0.87; P = .32).
- A sensitivity analysis conducted after excluding two studies with a high risk for bias also yielded null associations.
- The researchers performed subgroup analyses excluding studies that evaluated neoadjuvant radiation alone or included patients who did not receive curative resection and again found no association between pCR and either disease-free or overall survival.
IN PRACTICE:
“Our trial-level analysis did not reveal a correlation between pCR and [disease-free survival] or [overall survival] in rectal cancer RCTs,” the authors of the study concluded. “Our study’s findings suggest a recommendation against using pCR as a [surrogate endpoint] for neoadjuvant therapies in rectal cancer until conclusive trial-level evidence of its association with long-term outcomes is firmly established.”
SOURCE:
This study, led by Kavin Sugumar, MD, Tulane University, New Orleans, and Jessica Jin Lie, MD, MPH, University of British Columbia, Vancouver, British Columbia, Canada, was published online in JAMA Network Open.
LIMITATIONS:
A subgroup analysis of total neoadjuvant therapy trials was not feasible due to insufficient sample size. Additionally, postsurgical therapies in patients without pCR may have improved outcomes, potentially diluting its association with survival. Mediation analysis was not possible due to lack of patient-level data.
DISCLOSURES:
The authors did not disclose any funding information. One author disclosed receiving personal fees from Novartis, consulting fees from Boehringer Ingelheim, and grants from Eli Lilly and Company and Taiho, outside the submitted work. Another author reported receiving royalties as a coauthor on several chapters of UpToDate. No other disclosures were reported.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.