Journal
JOURNAL OF GASTROINTESTINAL ONCOLOGY
Volume 8, Issue 1, Pages 39-48Publisher
AME PUBL CO
DOI: 10.21037/jgo.2016.11.03
Keywords
Rectal cancer; pathologic complete response (pCR); disease-free survival (DFS); surrogate endpoints; overall survival (OS)
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Background: We performed a literature-based analysis of randomized clinical trials to assess the pathologic complete response (pCR) (ypT0N0 after neoadjuvant therapy) and 3-year disease-free survival (DFS) as potential surrogate endpoints for 5-year overall survival (OS) in rectal cancer treated with neoadjuvant (chemo) radiotherapy (CT) RT. Methods: A systematic literature search of PubMed, EMBASE, the Web of Science, SCOPUS, CINAHL, and the Cochrane Library was performed. Treatment effects on 3-year DFS and 5-year OS were expressed as rates of patients alive (%), and those on pCR as differences in pCR rates (Delta(pCR%)). A weighted regression analysis was performed at individual-and trial-level to test the association between treatment effects on surrogate (Delta(pCR%) and Delta(3yDFS)) and the main clinical outcome (Delta(5yOS)). Results: Twenty-two trials involving 10,050 patients, were included in the analysis. The individual level surrogacy showed that the pCR% and 3-year DFS were poorly correlated with 5-year OS (R=0.52; 95% CI, 0.31-0.91; P=0.002; and R=0.60; 95% CI, 0.36-1; P=0.002). The trial-level surrogacy analysis confirmed that the two treatment effects on surrogates (Delta(pCR%) and Delta(3yDFS)) are not strong surrogates for treatment effects on 5-year OS % (R=0.2; 95% CI, -0.29-0.78; P=0.5 and R=0.64; 95% CI, 0.29-1; P=0.06). These findings were confirmed in neoadjuvant CTRT studies but not in phase III trials were 3-year DFS could still represent a valid surrogate. Conclusions: This analysis does not support the use of pCR and 3-year DFS% as appropriate surrogate endpoints for 5-year OS% in patients with rectal cancer treated with neoadjuvant therapy.
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