A prospective randomized control study of neo-adjuvant chemo radiation followed by surgery versus upfront surgery in resectable and borderline resectable pancreatic head cancer: Pilot study

ABSTRACT Introduction: Neo-adjuvant chemoradiotherapy may improve survival in resectable or borderline resectable pancreatic cancer, but its feasibility, benefits, and challenges remain unproven in the resource constraint setup of developing countries. Patients and Methods: In this single-center randomized trial, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy or upfront surgery. Neo-adjuvant therapy consisted of two cycles of chemotherapy of gemcitabine and Nab-paclitaxel, followed by concurrent chemoradiotherapy with oral capecitabine combined with radiation therapy to a dose of 25 fractions × 1.8 Gray, followed by surgery and four cycles of adjuvant therapy or upfront surgery and six cycles of adjuvant chemotherapy. The primary end point was overall survival. Results: From March 2019 to March 2021, 80 patients were randomly assigned into two groups: 41 in neo-adjuvant therapy and 39 in upfront surgery. Per protocol analysis, 25/31 (80.65%) patients completed the intended neo-adjuvant treatment, with a dropout rate of 19.35%. Recurrent cholangitis due to stent block was the foremost reason for dropout. The median overall survival was 18.90 months with neo-adjuvant and 14.7 months in the upfront surgery group (hazard ratio, 0.78; 95% confidence interval, 0.58 to 1.05; P = .096). The resection rate was 36/41 (87.80%) in the upfront surgery group versus 14/31 (45.61%) in the NACRT group ( P = <.001). The secondary end points favoured neo-adjuvant therapy, R0 resection rate, 92.86% vs. 75%; P = .18, pathologic lymph nodes, 00% vs. 30.56%; P = .006, perineural invasion, 14.29% vs. 36.11%; P = .14. Conclusion: The median overall survival and disease-free survival showed an advantage with neo-adjuvant therapy but did not reach statistical significance. The secondary end points favoured neo-adjuvant treatment, but logistics, multiple visits, prolonged treatment, and financial constraints are some of the main hurdles for developing countries to deliver multimodality treatment.