N. Goel1, A. Nadler1, W. H. Ward1, K. J. Ruth1, A. Karachristos1, J. P. Hoffman1, S. S. Reddy1 1Fox Chase Cancer Center,Surgical Oncology,Philadelphia, PA, USA
Introduction:
There is increasing interest in total neoadjuvant therapy (TNT) for pancreatic cancer. This entails systemic chemotherapy followed by chemoradiotherapy, and then definitive surgery as long as the disease remains localized. The perceived benefits are that all patients receive multimodality therapy, eradication of occult systemic disease, and the potential to downstage borderline resectable (BR) tumors for curative resection. This study evaluates whether TNT has an overall survival (OS) benefit compared to neoadjuvant chemoradiation therapy and upfront surgery.
Methods:
This is a retrospective study of 182 pancreatic adenocarcinoma patients treated at our institution from 2000-2015 who underwent a pancreaticoduodenectomy (PD) or a total pancreatectomy. Patients undergoing distal pancreatectomy, those with macroscopic disease discovered at the time of surgery, and those with stage IV disease were excluded.
Results:
The analytic cohort consisted of 66 patients in the TNT group, 29 in the neoadjuvant chemoradiation group, and 87 in the surgery first group. Median age at diagnosis was 67 in the TNT cohort, 72 in the neoadjuvant cohort, and 70 in the surgery first cohort. 46(69.7%) of the TNT patients were initially borderline resectable (BR) or unresectable and were clinically stage 2A or higher. 67(77%) of the upfront surgery patients were clearly resectable and were clinically stage 2A or lower. Ten(15.2%) of the TNT patients had a complete pathologic response. 55(83.3%) of the TNT patients had an R0 resection. On univariate analysis, treatment(p=0.0016), age(p=0.037), nodal status(p=0.01), and margin status(p=0.001) were statistically significant. On multivariate analysis, treatment(p=0.024), age(p=0.0014), and margin status(p<0.0001) remained significant. Surgery first had a statistically significant greater hazard ratio compared to the TNT group at 1.81. Median OS from date of diagnosis was 18 months in the upfront surgery group, 25 months in the neoadjuvant group, and 36.7 months in the TNT group (p=0.0019). The TNT group also had the greatest CA19-9 drop with 77% having at least a 50% response.
Conclusion:
Although limited data exist on the utility of TNT, our review, which is one of the largest to date, shows a statistically significant improvement in OS for the TNT group, despite more advanced disease. We achieved a median OS of 36.7 months and 5 year OS 31.5% with TNT in a patient population that was more advanced, including both BR and unresectable patients. TNT therefore offers favorable short- and long-term outcomes, as well as the benefit of optimally selecting patients for surgery based on fitness for TNT and tumor biology.
