Paradigm shift for defining the resectability of pancreatic cancer

Abstract

Supported by the expanding indications for neoadjuvant therapy (NAT) for advanced pancreatic cancer (PC), the concept of resectability has evolved from being mostly based on the anatomical tumor extent to considering the biological and conditional factors relevant to prognosis. Therefore, it is more reasonable to define the "criteria for surgical resection" instead of using the "(technical) resectability criteria." NAT has been used in resectable PCs (RPC) with a high risk of early systemic recurrence, as predicted by various biological or anatomical markers. Moreover, the indications for NAT followed by conversion surgery or adjuvant surgery for borderline resectable or locally advanced PC (LAPC) are gradually expanding. Therefore, it is important to define the RPC group that will benefit from NAT and the LAPC group that will benefit from post-NAT surgery. At diagnosis, population-based approaches, such as prognostic stratification and staging systems and personalized outcome-based approaches using prognostic prediction models can be used to determine the criteria for treatment options. Standardized indications for conversion surgery are needed for patients who are initially treated with NAT. In addition to imaging-based morphological criteria, biological criteria, including CA19-9, and various metabolic criteria can be used to establish predicted outcome-based criteria. Multicenter collaboration is required to develop a large database with standardized data collection for various biomarkers and response data after NAT to establish more accurate outcome prediction models to define the new resectability criteria.

Prognostic value of circulating proteins in patients undergoing surgery for pancreatic cancer

“…However, the biomarker has a number of short comings as mentioned above, which makes its use as a diagnostic marker less valid, while its use in monitoring oncologic treatment is more reliable 13–15 . In borderline resectable tumors evaluated by CT scan, an elevated CA 19–9 together with confirmed lymph node metastases results in a recommendation to use neoadjuvant chemotherapy rather than undertake upfront resection 49 . In our study, CA19‐9 survived the selection procedures only for Index III.…”

“…13 , 14 , 15 In borderline resectable tumors evaluated by CT scan, an elevated CA 19–9 together with confirmed lymph node metastases results in a recommendation to use neoadjuvant chemotherapy rather than undertake upfront resection. 49 In our study, CA19‐9 survived the selection procedures only for Index III.…”

Pancreatectomy with concomitant portal vein resection in the current neoadjuvant era

“…The standard treatment for patients with resectable pancreatic cancer is surgery followed by adjuvant chemotherapy with the chance of long-term survival up to 20-25% (5).…”

“…In the last decade, neoadjuvant treatment (NAT) strategies are showing a crucial role in solid organ cancers such as breast, rectal, gastric cancer and pancreatic cancer, as well (9). Currently, several trials, such as the PRODIGE 48, 44 and 56 and NEOPAN are investigating with optimism the benefit of these regimens as NAT for potentially resectable pancreatic cancer (5). In this regard, NAT in borderline resectable (BR) or even resectable (R) PDAC has gained wide acceptance lately based on the results of several multicentric randomized clinical trials carried out in highly selected centers such as the PREOPANC, JANG and ESPAC-5F (5,10).…”

“…Currently, several trials, such as the PRODIGE 48, 44 and 56 and NEOPAN are investigating with optimism the benefit of these regimens as NAT for potentially resectable pancreatic cancer (5). In this regard, NAT in borderline resectable (BR) or even resectable (R) PDAC has gained wide acceptance lately based on the results of several multicentric randomized clinical trials carried out in highly selected centers such as the PREOPANC, JANG and ESPAC-5F (5,10). The main potential claimed benefit of NAT is to improve the OS by increasing the R0 resections, treating micrometastasis, delivering chemotherapy to all patients, and making an adequate selection of patients who are likely to benefit from a pancreatectomy (11).…”