New implications from long-term outcomes of perioperative therapy in resectable pancreatic cancer.

The biggest impact on increasing survival for pancreatic cancer has come about by combining surgical resection with systemic chemotherapy. This groundbreaking paradigm has come under increasing scrutiny relating to the choice of adding chemoradiotherapy to chemotherapy versus chemotherapy alone, neoadjuvant versus adjuvant therapy and the optimal regimens. The paradigm has also been challenged in that a distinction needs to be made between 'resected' with 'resectable' pancreatic cancer, since if only the former is considered, this leads to a biased prognostically favourable patient group being analysed. Moreover, the distinction between resectable, borderline resectable and unresectable cancers is claimed to be so unreliable that this classification should be discouraged in favour of upfront chemotherapy for all patients and not necessarily using either FOLFIRINOX or gemcitabine-capecitabine. The results of a series of recent trials including the RTOG0848 trial of adjuvant chemotherapy with or without chemoradiation and the NORPACT-1 trial of neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic cancer have significantly contributed to the clarification of some these questions. The results of long-term follow-up studies of the adjuvant PRODIGE24 trial comparing FOLFIRINOX with gemcitabine and the ESPAC4 trial of gemcitabine-capecitabine versus gemcitabine have also consolidated and expanded the applicability of adjuvant chemotherapy.