Neoadjuvant chemoradiation for locally advanced rectal cancer: a systematic review of the literature with network meta-analysis.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) prior to surgery is a standard therapy for locally advanced rectal cancer, but the optimum regime is not conclusive. This meta-analysis evaluated various CRT regimens with regard to the rate of pathologic complete response (pCR) and toxic effects of grade ≥3. METHODS: The databases PubMed, Cochrane Library, and Embase were searched for randomized controlled trials (RCTs) that compared neoadjuvant CRT regimes for treating patients with locally advanced rectal cancer, published before 28 December 2017. The primary end points were pCR and toxic effects. A network meta-analysis was applied. RESULTS: Fourteen RCTs (with 5,599 participants) involving the following eight regimens were included: fluorouracil (5FU) alone, or 5FU with oxaliplatin (OXA), cisplatin, or irinotecan (CPT-11); capecitabine (CAP) alone, or CAP with OXA or CPT-11; and CPT-11 with combined tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. The rate of pCR associated with CAP + OXA was significantly higher compared with 5FU alone; there were no significant differences among the other regimens. The toxicity of 5FU + OXA or CAP + OXA was significantly worse than that of 5FU alone or CAP alone. CAP + OXA and CAP were ranked, respectively, the most and second most effective regimens in terms of pCR rate. 5FU alone and CAP alone likely had the lowest and second lowest toxicity, respectively. CONCLUSION: Among the currently available CRT regimens for locally advanced rectal cancer, this meta-analysis indicated that CAP + OXA provides the superior clinical results. Adding OXA to 5FU or CAP significantly increases toxicity.

Adjuvant Second-Dose Chemotherapy before Surgery for Patients with Locally Advanced Rectal Malignancy Is Not Beneficial: A Systematic Review and Meta-Analysis.

BACKGROUND: Preoperative chemoradiotherapy is the standard treatment for patients with locally advanced rectal cancer, although tumor responses vary widely; some patients may achieve a pathologic complete response rate (pCR) after chemoradiotherapy. Controversy exists with regard to the efficacy of different preoperative combination chemotherapy regimens and neoadjuvant chemoradiotherapy, compared with chemoradiotherapy alone. METHODS: PubMed, the Cochrane Library, and Embase databases were searched for comparative studies of patients with locally advanced rectal cancer that were published between January 1991 and January 2016. Efficacies of different preoperative combination chemotherapy regimens and neoadjuvant chemoradiotherapy (group A) were compared with chemoradiotherapy alone (group B) in a meta-analysis using Review Manager v5.2. RESULTS: Three prospective randomized controlled trials and two prospective nonrandomized controlled trials comprising 444 cases were eligible for analysis. No significant difference was detected in the rate of pCR (50/223, 22.4% versus 35/223, 15.7%; relative risk, RR: 1.42 [95% confidence interval, CI: 0.97-2.09], p = 0.07) between the two groups. The rate of tumor regression was similar for both groups (122/203, 60.1% versus 111/203, 54.7%; RR: 1.11 [95% CI: 0.94-1.29], p = 0.22). CONCLUSIONS: Adjuvant chemotherapy with preoperative chemoradiotherapy did not significantly improve the rate of pCR nor the rate of T and N downstaging.

Comparing Mechanical Bowel Preparation With Both Oral and Systemic Antibiotics Versus Mechanical Bowel Preparation and Systemic Antibiotics Alone for the Prevention of Surgical Site Infection After Elective Colorectal Surgery: A Meta-Analysis of Randomized Controlled Clinical Trials.

BACKGROUND: The discussion on the role of mechanical bowel preparation and oral antibiotics in elective colorectal surgery is still ongoing. OBJECTIVE: This meta-analysis aimed to determine whether oral systemic antibiotics with mechanical bowel preparation are superior to systemic antibiotics and mechanical bowel preparation for prophylaxis of bacterial infection during elective colorectal operation. DATA SOURCES: Embase, PubMed, and the Cochrane Library were searched using the terms oral, antibiotics/antimicrobial, colorectal/rectal/colon/rectum, and surgery/operation. STUDY SELECTION: All of the available randomized controlled trials that compared the efficacy of combined oral and systemic antibiotics and mechanical bowel preparation with systemic antibiotics alone and mechanical bowel preparation in colorectal surgery and defined surgical site infection based on Centers for Disease Control and Prevention criteria were included. INTERVENTION: All of the statistical analyses were performed using Review Manager 5.2 software. A fixed model was used if there was no evidence of heterogeneity; otherwise, a random-effects model was used. MAIN OUTCOME MEASURES: We focused on incidence of surgical site infection among the groups. RESULTS: Seven randomized controlled trials that consisted of 1769 cases were eligible for analysis. We found that both total surgical site infection and incisional surgical site infection were significantly reduced in patients who received oral systemic antibiotics and mechanical bowel preparation compared with patients who received systemic antibiotics alone and mechanical bowel preparation (total: 7.2% vs 16.0%, p < 0.00001; incisional: 4.6% vs 12.1%, p < 0.00001). However, no significant difference was detected in the rate of organ/space surgical site infection (4.0% vs 4.8%; p = 0.56) after elective colorectal surgery. LIMITATIONS: The meta-analysis was limited by the risk of bias because a majority of the studies did not use the blinding method. CONCLUSIONS: Oral systemic antibiotics and mechanical bowel preparation significantly lowered the incidence of surgical site infection after elective colorectal surgery compared with systemic antibiotics alone and mechanical bowel preparation.