Objective This study aims to compare the efficacy of neoadjuvant methotrexate therapy followed by surgery versus primary surgical management in patients with stage III oral carcinoma. Methods Thirty patients diagnosed with stage III oral carcinoma were enrolled in this prospective study at a tertiary cancer research center. The patients were divided into two groups: 15 patients received neoadjuvant methotrexate therapy followed by surgery, while 15 underwent primary surgical management. Outcomes were evaluated based on tumor downstaging, surgical margins, postoperative complications, and the requirement for adjuvant radiotherapy. Results Patients in the neoadjuvant methotrexate group demonstrated significant tumor downstaging, allowing for less extensive surgical procedures, with 33.3% (n=5) undergoing wide local excision (WLE) compared to 13.3% (n=2) in the primary surgery group. Negative surgical margins were achieved in 93.33% (n=14) of patients in the neoadjuvant group versus 53.33% (n=8) in the surgical group. Additionally, only 13.3% (n=1) of patients in the neoadjuvant group required postoperative radiotherapy, compared to 53.33% (n=8) in the surgical group. The recurrence rate over a six-month follow-up period was comparable between the two groups. Discussion Neoadjuvant methotrexate therapy resulted in better surgical and oncological outcomes by downstaging the tumor, reducing the extent of surgery, and minimizing the need for postoperative radiotherapy. The findings suggest that methotrexate, as a neoadjuvant agent, is effective in improving patient outcomes with fewer side effects compared to standard cisplatin-based regimens. Conclusion Neoadjuvant methotrexate therapy offers a viable treatment option for stage III oral carcinoma, demonstrating improved oncological and surgical outcomes, including less invasive surgery, higher rates of negative surgical margins, and reduced postoperative radiotherapy requirements. Further research with long-term follow-up is necessary to validate these findings and explore the long-term impact on survival and recurrence rates.
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