Objectives: The advent of effective chemotherapy regimens has increased the use of neoadjuvant multiagent chemotherapy in pancreatic cancer. Tumor downstaging occurs with such regimens. However, the rate of downstaging and the impact (if any) on survival are unclear.
Methods: This retrospective single-institution study included all resected patients with pancreatic adenocarcinoma who underwent neoadjuvant chemotherapy with FOLFIRINOX or Gemcitabine/Abraxane from 2011-2020. Downstaging was quantified using two methods: 1) the difference between presenting AJCC clinical stage and final pathologic stage and 2) the College of American Pathologists (CAP) Tumor Regression Grading Scheme (downstaging defined as Score 0-2).
Results: 87 patients met the criteria for inclusion. The majority of patients were female (57.5%), white (97.7%), and privately insured (89%). FOLFIRONOX was the most common regimen compared to Gemcitabine/Abraxane, 63.2 % versus 21.8%. Tumor progression or toxicity requiring a change in regimen occurred in 15% of patients. A minority of patients were treated with neoadjuvant radiation, 20.7%. Downstaging based on a change in the AJCC stage group occurred in only 4.6%. In contrast, 45.2% were classified as downstaged by the CAP Tumor Regression Grading of 0-2. Downstaging was similar for FOLFIRONOX vs. Gemcitabine/Abraxane (64.7 vs. 53.6, p=0.12) and with radiation vs. no radiation therapy (29.4 vs. 14.3, p= 0.27) using the CAP criteria. On univariate analysis, both neoadjuvant radiation (median survival 31 vs. 28mo; HR = 0.79, p= 0.6) and treatment regimen (Gemcitabine/Abraxane vs. FOLFIRONOX, median survival 27 vs. 29mo; HR 1.57, p = 0.2) had similar survival. Downstaging by AJCC stage was not associated with improved survival (HR 1.51, p = 0.4). However, there was a survival benefit for those downstaged by the CAP Tumor Regression Grading Schema, the median survival of 41mo vs. 25 mo; HR 3.05, p= 0.009. Improved survival was maintained on multivariate analysis.
Conclusion: Downstaging is an important prognostic variable. The CAP Tumor Regression Grading System is a more sensitive way to identify those patients downstaged by neoadjuvant treatment compared to change in the AJCC stage. Also, survival is significantly improved in those downstaged as assessed by the CAP Tumor Regression System.
