**9. Conclusions**

adjuvant chemotherapy, neoadjuvant chemoradiation, neoadjuvant chemoradiation versus

Concerning toxicity among patients treated with neoadjuvant treatments that have been reported, mostly as local experiences or as small institutional trials, there are no clear data concerning side effects of neoadjuvant therapies, nor there are data on perioperative morbidity and mortality, comparing patients who underwent upfront surgery and patients who received neoadjuvant treatment and then underwent surgery. The biggest data on quality of life come from reports in the metastatic setting. The quality of life report of the PRODIGE-4 trial (mentioned earlier), FOLFIRINOX chemotherapy reduced the quality of life impairment compared with gemcitabine, but also it has benefit in the quality of life that can be a surrogate for survival, as physical functioning and some symptoms severity were prognostic factors for survival [50]. In a meta-analysis of FOLFIRINOX in locally advanced pancreatic cancer, 60% of the patients presented G3 or higher side effects, neutropenia and diarrhea being the most frequent events among treated patients. There were no related deaths attributable to FOLFIRINOX [42]. In a retrospective analysis of patients undergoing FOLFIRINOX as neoadjuvant treatment followed by surgery, Marchegiani et al. concluded that among patients who underwent neoadjuvant chemotherapy, there were less postoperative pancreatic fistula and

less postoperative pancreatic hemorrhage but delayed in gastric emptying [51].

Due to a lack of strong data based on phase 3 clinical trials, it is not possible to talk about a gold-standard treatment in the neoadjuvant setting for pancreatic cancer patients. Most of the groups support the idea to perform surgery as an upfront treatment in resectable patients fol-

Current ESMO guidelines support the use of FOLFIRINOX followed by chemoradiotherapy in borderline resectable patients as a main option in pancreas cancer [52]. Contrarily, ASCO guidelines indicate that there is no clear evidence to support one regimen over another, and physicians may offer therapy based on extrapolation from data derived from studies in the

Pancreatic cancer patients with resectable or borderline resectable disease should always be discussed in a multidisciplinary team. Neoadjuvant treatment should always be considered to attempt an R0 resection; otherwise, the chance of cure in non-R0-resected patients and also due to the meaning of the diagnosis itself will be similar to metastatic patients. Multidisciplinary team should at least include a digestive oncological surgeon with expertise in pancreatic surgery, a medical oncologist, a radiologist with expertise in pancreas, a radiation oncologist, and a pathologist, given the disparity of opinions and the importance of treatment agreement

At SLAGO 2015 (Latin American Gastro-Enterology Cancer Symposium) congress [54], a meeting held every 2 years in Latin America that focuses on digestive malignancies, specialists from different Latin American countries met to discuss about pancreatic cancer. Concerning

upfront surgery, and other modalities as well [45–49].

**8. Current guidelines**

188 Advances in Pancreatic Cancer

metastatic setting [53].

lowed by adjuvant chemotherapy.

looking forward the best chance to those patients.

Pancreatic cancer is one of the most lethal malignancies among all types of solid tumors. Most of the patients are diagnosed at unresectable or at advanced stages with no chances of cure. Early diagnosis is critical to give the patient the chance of cure; however, most of the patients are diagnosed where the tumor is not amenable to be resected. Even more, many of the patients who will undergo an R0 resection will relapse before 2 years after surgery.

We would like to remark that there is no strong evidence to make final conclusions in order to define the best upfront treatment in non-metastatic resectable and borderline resectable pancreatic cancer patients. For resectable patients at diagnosis, upfront surgery is still the standard of care followed by adjuvant chemotherapy. In this subgroup of patients, radiotherapy and chemoradiotherapy do not seem to be the best choice. On the other hand, neoadjuvant chemotherapy has not been explored yet in well-designed clinical trials, and its use has been just limited to small experiences. Borderline resectable pancreatic cancer patients are a subgroup where upfront surgery has a low chance of achieving an R0 resection; therefore, these patients must be considered to receive neoadjuvant treatments in order to improve complete tumor resection and as a consequence to improve survival. As in the resectable subset of patients, radiotherapy or chemoradiotherapy has not shown a real impact in this group. FOLFIRINOX followed or not by chemoradiotherapy seems to be the best option to improve resectability, for achieving complete resection and pathological downstaging and for improving overall survival in resected patients. Final reports from clinical trials will set the key whether or not neoadjuvant treatment, in resectable and borderline resectable pancreatic cancer patients, should be mandatory or recommended.
