Induction Chemotherapy for Primarily Unresectable Locally Advanced Pancreatic Adenocarcinoma-Who Will Benefit from a Secondary Resection?

Background and Objectives: An increasing number of patients (pts) with locally advanced pancreatic cancer (LAPC) are treated with an intensive neoadjuvant therapy to obtain a secondary curative resection. Only a certain number of patients benefit from this intention. The aim of this investigation was to identify prognostic factors which may predict a benefit for secondary resection. Materials and Methods: Survival time and clinicopathological data of pts with pancreatic cancer were prospective and consecutively collected in our Comprehensive Cancer Center Database. For this investigation, we screened for pts with primarily unresectable pancreatic cancer who underwent a secondary resection after receiving induction therapy in the time between March 2017 and May 2019. Results: 40 pts had a sufficient database to carry out a reliable analysis. The carbohydrate-antigen 19-9 (CA 19-9) level of the pts treated with induction therapy decreased by 44.7% from 4358.3 U/mL to 138.5 U/mL (p = 0.001). The local cancer extension was significantly reduced (p < 0.001), and the Eastern Cooperative Oncology Group (ECOG) performance status was lowered (p = 0.03). The median overall survival (mOS) was 20 months (95% CI: 17.2-22.9). Pts who showed a normal CA 19-9 level (<37 U/mL) at diagnosis and after neoadjuvant therapy or had a Body Mass Index (BMI) below 25 kg/m2 after chemotherapy had a significant prolonged overall survival (29 vs. 19 months, p = 0.02; 26 vs. 18 months, p = 0.04; 15 vs. 24 months, p = 0.01). Pts who still presented elevated CA 19-9 levels >400 U/mL after induction therapy did not profit from a secondary resection (24 vs. 7 months, p < 0.001). Nodal negativity as well as the performance of an adjuvant therapy lead to better mOS (25 vs. 15 months, p = 0.003; 10 vs. 25 months, p < 0.001). Conclusion: The pts in our investigation had different benefits from the multimodal treatment. We identified the CA 19-9 level at time of diagnosis and after neoadjuvant therapy as well as the preoperative BMI as predictive factors for overall survival. Furthermore, diagnostics of presurgical nodal status should gain more importance as nodal negativity is associated with better outcome.

Neoadjuvant Chemotherapy Enhances Local Postoperative Histopathological Tumour Stage in Borderline Resectable Pancreatic Cancer - A Matched-Pair Analysis.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is established in the treatment of ductal pancreatic adenocarcinoma for downsizing borderline-resectable pancreatic cancer (BRPC) and may affect nodal positivity and rates of R0 resection. This study aimed to identify the impact of NAC on postoperative histopathological parameters with a prognostic relevance. PATIENTS AND METHODS: A one-to-three matched-pair analysis, including an overall total of 132 patients (25% treated with NAC and subsequent resection and 75% undergoing upfront surgery) was performed. Influence of NAC on nodal positivity, lymphatic, vascular and perineural invasion, as well as resection stage and grading, was examined. Furthermore, perioperative complications, in-hospital stay, re-admission rates, mortality, as well as preoperative body mass index and American Association of Anesthesiologist classification scores, were evaluated. RESULTS: Patients treated with NAC significantly less frequently had lymphatic tissue invasion (lymph node invasion: 51.5% vs. 72.7%; p=0.032, and lymphatic vessel invasion 9.4% vs. 55.3%; p=0.0004), whereas vascular and perineural invasion, as well as grading and resection state were not significantly different. Carbohydrate antigen 19-9 regression in correlation with nodal positivity also did not differ, and both groups showed comparable perioperative complication rates. Occurrence and severity of postoperative pancreatic fistula (18.2% vs. 24.3%; p=0.034) were significantly lower in patients who had undergone NAC. CONCLUSION: NAC significantly affects postoperative histopathological tumour stage in BRPC and appears to be a safe treatment option without increased perioperative complications, re-admission, in-hospital stay, or mortality. Further studies are mandatory to underline the suitability of NAC for ductal pancreatic adenocarcinoma subgroups in order to guide clinicians in their daily decision-making comprehensively.