Twenty-two RCTs were included in the review: 6 RCTs (1,042 participants) of surgery and radiotherapy (513 participants) versus surgery alone (529 participants); 6 RCTs (3318 participants) of surgery plus non-cisplatin-based chemotherapy (1808 participants) versus surgery alone (1510 participants); 6 RCTs (1367 participants) of surgery plus cisplatin-based chemotherapy (741 participants) versus surgery alone (626 participants); and 4 RCTs (555 participants) of surgery and radiotherapy and chemotherapy (275 participants) versus surgery and radiotherapy alone (251 participants).
There was no survival benefit with adjuvant radiotherapy alone, although 3 RCTs reported a reduction in the rate of local recurrence among patients treated with adjuvant radiotherapy.
Post-operative adjuvant chemotherapy with alkylating agents was found in the meta-analysis to increase the relative risk of death by 15% (HR 1.15, 95% CI: 1.04, 1.27). The absolute reduction in survival rate was 4% at 2 years, and 5% at 5 years.
Chemotherapy in combination with radiotherapy it resulted in a 6% reduction in the relative risk of death (HR 0.94, 95% CI: 0.79, 1.11; p = 0.46) which was not statistically significant with an absolute benefit of 2% at 2 years and at 5 years. A study involving prolonged adjuvant chemotherapy (busulfan or cytoxan daily for 2 years) reported that 4 of 726 patients had hematologic malignancies. In one study, only 53% of patients received all 4 cycles of chemotherapy with cyclophosphamide- doxorubicin-cisplatin (CAP); in another, 22% of patients refused therapy with CAP because of nausea and vomiting.
The meta-analysis showed that post-operative, cisplatin-based chemotherapy reduced the relative risk of death by 13% (HR 0.87, 95% CI: 0.74, 1.02; p = 0.08) and an absolute benefit of 3% at 2 years and 5% at 5 years which were not statistically significant.