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 (∆pCR%). A weighted regression analysis was performed at individual- and trial-level to test the association between treatment effects on surrogate (∆pCR% and ∆3yDFS) and the main clinical outcome (∆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 (∆pCR% and ∆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.
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 (∆pCR%). A weighted regression analysis was performed at individual- and trial-level to test the association between treatment effects on surrogate (∆pCR% and ∆3yDFS) and the main clinical outcome (∆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 (∆pCR% and ∆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.
Authors: E Kapiteijn; C A Marijnen; I D Nagtegaal; H Putter; W H Steup; T Wiggers; H J Rutten; L Pahlman; B Glimelius; J H van Krieken; J W Leer; C J van de Velde Journal: N Engl J Med Date: 2001-08-30 Impact factor: 91.245
Authors: Mark S Roh; Linda H Colangelo; Michael J O'Connell; Greg Yothers; Melvin Deutsch; Carmen J Allegra; Morton S Kahlenberg; Luis Baez-Diaz; Carol S Ursiny; Nicholas J Petrelli; Norman Wolmark Journal: J Clin Oncol Date: 2009-09-21 Impact factor: 44.544
Authors: Markus Diefenhardt; Anke Schlenska-Lange; Thomas Kuhnt; Simon Kirste; Pompiliu Piso; Wolf O Bechstein; Guido Hildebrandt; Michael Ghadimi; Ralf-Dieter Hofheinz; Claus Rödel; Emmanouil Fokas Journal: Cancers (Basel) Date: 2022-07-27 Impact factor: 6.575