The efficacy of neoadjuvant chemotherapy as compared to upfront surgery for the management of oral squamous cell carcinoma: a systematic review and meta-analysis

The efficacy of neoadjuvant chemotherapy in the field of head and neck oncology has always been debated. The aim of this study was to determine the efficacy of neoadjuvant chemotherapy followed by surgery in patients with oral squamous cell carcinoma (OSCC) by comparison to upfront surgery, in terms of overall survival, disease-free survival, response rates, positive surgical margins, loco-regional recurrence, distant metastasis, and toxicity. Prospective and retrospective studies were identified from a search of the PubMed, PubMed Central, and Cochrane Library databases (publication date between January 1, 1995 and January 1, 2022), as well as hand searches. Three randomized clinical trials and five retrospective studies reporting a total of 1373 patients were retrieved (493 treated with NACT, 880 treated with upfront surgery). All statistical analyses were done using RevMan 5.4. There was no statistically significant difference between the treatment groups for all outcomes (overall survival P = 0.41, disease-free survival P = 0.91, loco-regional recurrence P = 0.12, distant metastasis P = 0.23), except positive margins (P = 0.007); a reduced risk of positive margins was observed for neoadjuvant chemotherapy. The pooled proportion of patients with a complete pathological response (17%) was inadequate to obtain an improvement in survival. The lower margin positivity rate, leading to resectability with clear margins, may be a benefit of neoadjuvant chemotherapy in locally advanced OSCC; however, this treatment failed to provide a benefit in terms of survival and the response rate.