Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer.
BACKGROUND
Preoperative radiotherapy (RT) decreases local recurrence rate and improves survival in stage II and III rectal cancer patients. The combination of chemotherapy with RT has a sound radiobiological rationale, and phase II trials of combined chemoradiation (CRT) have shown promising activity in rectal cancer.


OBJECTIVE
To compare preoperative RT with preoperative CRT in patients with resectable stage II and III rectal cancer.


METHODS
We searched the Cochrane Central Register of Controlled Trials, Web of Science, Embase.com, and Pubmed from 1975 until june 2007. A manual search was performed of Ann Surg, Arch Surg, Cancer, J Clin Oncol, Int J Radiat Oncol Biol Phys and the proceedings of ASTRO, ECCO and ASCO from 1990 until june 2007.


METHODS
Relevant studies randomized resectable stage II or III rectal cancer patients to at least one arm of preoperative RT alone or at least one arm of preoperative CRT.


METHODS
Primary outcome parameters included overall survival (OS) at 5 years and local recurrence (LR) rate at 5 years. Secondary outcome parameters included disease free survival (DFS) at 5 years, metastasis rate, pathological complete response rate, clinical response rate, sphincter preservation rate, acute toxicity, postoperative mortality and morbidity, and anastomotic leak rate. Outcome parameters were summarized using the Odds Ratio (OR) and associated 95% confidence interval (CI) using the fixed effects model.


RESULTS
Four trials were identified and included in the meta-analysis. The addition of chemotherapy to preoperative RT significantly increased grade III and IV acute toxicity (OR 1.68-10, P = 0.002) while no differences were observed in postoperative morbidity or mortality. Compared to preoperative RT alone, preoperative CRT significantly increased the rate of complete pathological response (OR 2.52-5.27, P < 0.001) although this did not translate into a higher sphincter preservation rate (OR 0.92-1.31, P = 0.29). The incidence of local recurrence at five years was significantly lower in the CRT group compared to RT alone (OR 0.39-0.72, P < 0.001). No statistically significant differences were observed in DFS (OR 0.92-1.34, P = 0.27) or OS (OR 0.79-1.14, P = 0.58) at five years.


CONCLUSIONS
Compared to preoperative RT alone, preoperative CRT enhances pathological response and improves local control in resectable stage II and III rectal cancer, but does not benefit disease free or overall survival. The effects of preoperative CRT on functional outcome and quality of life are incompletely understood and should be addressed in future trials.
Ceelen
Wim P
WP
Dept. of Surgery 2K12 1C, Ghent University Hospital, De Pintelaan 185, Ghent, Belgium, B-9000. wim.ceelen@ugent.be
Van Nieuwenhove
Yves
Y
Fierens
Kjell
K
D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery