Downstaging of Pancreatic Adenocarcinoma With Either Neoadjuvant Chemotherapy or Chemoradiotherapy Improves Survival

• Published in: Annals of surgical oncology Vol. 29; no. 9; pp. 6015 - 6028
• Main Authors: O’Shea, Anne E., Bohan, Phillip M. Kemp, Carpenter, Elizabeth L., McCarthy, Patrick M., Adams, Alexandra M., Chick, Robert C., Bader, Julia O., Krell, Robert W., Peoples, George E., Clifton, Guy T., Nelson, Daniel W., Vreeland, Timothy J.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-09-2022; Springer Nature B.V
• Subjects: Adenocarcinoma; Adenocarcinoma - pathology; Adenocarcinoma - therapy; Cancer; Chemoradiotherapy; Chemotherapy; Chemotherapy, Adjuvant; Humans; Medicine; Medicine & Public Health; Metastases; Neoadjuvant Therapy; Neoplasm Staging; Oncology; Pancreas; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Pancreatic Tumors; Patients; Radiation therapy; Retrospective Studies; Surgery; Surgical Oncology; Survival; Treatment Outcome
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-022-11800-0

Background
Neoadjuvant chemotherapy (NAC) or chemoradiation (NAC+XRT) is incorporated into the treatment of localized pancreatic adenocarcinoma (PDAC), often with the goal of downstaging before resection. However, the effect of downstaging on overall survival, particularly the differential effects of NAC and NAC+XRT, remains undefined. This study examined the impact of downstaging from NAC and NAC+XRT on overall survival.
Methods
The National Cancer Data Base (NCDB) was queried from 2006 to 2015 for patients with non-metastatic PDAC who received NAC or NAC+XRT. Rates of overall and nodal downstaging, and pathologic complete response (pCR) were assessed. Predictors of downstaging were evaluated using multivariable logistic regression. Overall survival (OS) was assessed with Kaplan–Meier and Cox proportional hazards modeling.
Results
The study enrolled 2475 patients (975 NAC and 1500 NAC+XRT patients). Compared with NAC, NAC+XRT was associated with higher rates of overall downstaging (38.3 % vs 23.6 %;
p
≤ 0.001), nodal downstaging (16.0 % vs 7.8 %;
p
≤ 0.001), and pCR (1.7 % vs 0.7 %;
p
= 0.041). Receipt of NAC+XRT was independently predictive of overall (odds ratio [OR] 2.28;
p
< 0.001) and nodal (OR 3.09;
p
< 0.001) downstaging. Downstaging by either method was associated with improved 5-year OS (30.5 vs 25.2 months;
p
≤ 0.001). Downstaging with NAC was associated with an 8-month increase in median OS (33.7 vs 25.6 months;
p
= 0.005), and downstaging by NAC+XRT was associated with a 5-month increase in median OS (30.0 vs 25.0 months;
p
= 0.008). Cox regression showed an association of overall downstaging with an 18 % reduction in the risk of death (hazard ratio [HR] 0.82; 95 % confidence interval, 0.71–0.95;
p
= 0.01)
Conclusion
Downstaging after neoadjuvant therapies improves survival. The addition of radiation therapy may increase the rate of downstaging without affecting overall oncologic outcomes.