BACKGROUND: Esophageal cancer is a major problem in India. The incidence has a geographic variation, being more common in some parts of south India and pockets in the north. The patients usually present in late stages as the symptoms are non-specific, hence patients are treated for other causes over prolonged periods. There has been marked improvement due to the incorporation of a multi-modality approach in the management of these cancers over the last decade. OBJECTIVE: This study included patients with non-metastatic esophageal cancer who presented to the department of medical oncology between January 2020 and December 2023. The aim was to analyze the clinical and demographic profiles and survival outcomes of patients. METHODOLOGY: This is a retrospective study conducted at a tertiary cancer care center in southern India, primarily serving patients from rural areas. Approval from the Institutional Ethics Committee was secured prior to the study (GSLMC/RC:1259A-EC/1259A-05/2024). Case files for all esophageal cancer patients treated at our center between January 2020 and December 2023 were collected from the medical records department and analyzed. We focused on patients diagnosed with non-metastatic esophageal cancer who had received treatment. RESULTS: A total of 47 patients participated in our study, with a mean age of 55 years. The male-to-female ratio was 2:3. Among the participants, 18 (38.3%) were smokers and 12 (25.5%) were alcohol users. The most frequently affected site was the middle thoracic esophagus, with 22 patients (46.8%), followed by the lower third in 15 patients (31.9%), and both the upper one-third and gastroesophageal junction cancers each accounting for five patients (10.6%). Squamous cell carcinoma was the predominant histological type, representing 82% of cases. Stage 2 was the most common stage at presentation, seen in 22 patients (46.8%), followed by stage 3 in 17 patients (36.2%). Twenty patients received neoadjuvant chemoradiotherapy (NACRT), with 13 (65%) receiving a weekly regimen of paclitaxel and carboplatin, while seven (35%) were treated with a CAPEOX (capecitabine and oxaliplatin) regimen alongside radiation (41.4 to 45 Gray). Of these, only eight patients (40%) proceeded to surgery, while 12 patients (60%) did not. Among those who underwent surgery, five patients (62.5%) achieved a pathological complete response. Additionally, 24 patients received definitive CRT, resulting in a complete response in 14 patients (58.3%) and a partial response in 10 patients (41.6%). Three patients defaulted on treatment. The median overall survival for the analyzed group was 10.5 months, with a subset analysis showing that those who had surgery had a survival duration of 12 months, compared to eight months for those who did not undergo surgery. CONCLUSION: The study concluded that the middle thoracic esophagus is the most prevalent site for esophageal cancer, with squamous cell carcinoma being the predominant histological type. Stage 2 is frequently observed at presentation, followed by stage 3. The standard treatment for locally advanced esophageal malignancies now involves a combined approach with NACRT. Despite advancements in multimodal treatments, the prognosis for esophageal cancer remains poor and requires significant improvement.