Improved Overall Survival of Patients with Pancreatic Cancer through Multiagent Chemotherapy and Increased Rates of Surgical Resection.

BACKGROUND: Seminal trials have demonstrated improved survival in pancreatic adenocarcinoma with novel multiagent chemotherapy regimens. To understand the clinical ramifications of this paradigm shift, we reviewed our institutional experience. METHODS: This retrospective cohort study utilized a prospective database at a single institution to study all patients diagnosed with and treated for pancreatic adenocarcinoma between 2000 and 2020. RESULTS: 1,572 patients were included of which 36% were diagnosed before (Era 1) and 64% after (Era 2) 2011. Survival improved in Era 2 (Median survival 10 vs 8 months, HR .79; P < .001). The survival advantage for Era 2 was primarily seen in patients with high-risk disease (12 vs10 months, HR .71; P < .001). A similar trend was noted for patients undergoing surgical resection (26 vs 21 months, HR .80; P = .081) and with imminently resectable tumors (19 vs 15 months, HR .88; P = .4); however, this was not statistically significant. There was no survival advantage for patients with stage IV disease (4 vs 4 months). Patients in Era 2 were more likely to undergo surgery (OR 2.78; CI 2.00-3.92, P < .001). This increase was driven primarily by increased surgical resection for those with high-risk disease (42 vs 20%, OR 3.74; P < .001). DISCUSSION/CONCLUSIONS: This single institutional study showed improved survival after the shift to novel chemotherapy regimens. This was driven by improved survival for patients with high-risk disease and may be due to more effective eradication of microscopic metastatic disease with adjuvant chemotherapy and increased resection rates.

Pathologic Tumor Regression is Associated With Improved Survival in Pancreatic Cancer.

OBJECTIVES: The advent of effective chemotherapy regimens has increased the use of neoadjuvant multiagent chemotherapy in pancreatic cancer. However, the effect of tumor downstaging with neoadjuvant treatment on survival is unclear. METHODS: Retrospective study included all resected patients with pancreatic adenocarcinoma who underwent neoadjuvant chemotherapy with FOLFIRINOX or gemcitabine/Abraxane. Downstaging was quantified using (1) difference between presenting AJCC clinical and final pathologic stage and (2) College of American Pathologists (CAP) Tumor Regression Grading Schema. RESULTS: Eighty-seven patients met inclusion criteria. FOLFIRINOX was the most common regimen, 63.2% vs 21.8%. Change in regimen occurred in 15% of patients. Downstaging based on a difference in AJCC stage group occurred in only 4.6%. In contrast, 45.2% were classified as downstaged by the CAP Tumor Regression of 0-2. Downstaging was similar for FOLFIRINOX gemcitabine/Abraxane (64.7 vs 53.6, P = .12) using the CAP criteria. On univariate analysis, treatment regimen (gemcitabine/Abraxane vs FOLFIRINOX, median survival 27 vs 29 mo; HR 1.57, P = .2) had similar survival. Downstaging by the AJCC stage was not associated with improved survival (HR 1.51, P = .4). However, there was a survival benefit for those downstaged by the CAP Tumor Regression Grading Schema, the median survival of 41 mo vs 25 mo; HR 3.05, P = .009. Improved survival 3.32 (1.35-8.16), P = .009) was maintained on multivariate analysis. CONCLUSION: Survival is significantly improved in those downstaged, as assessed by the CAP Tumor Regression Schema. Downstaging is an important prognostic variable that can help with joint decision making for clinicians and patients.