Adjuvant and neoadjuvant treatment for pancreatic adenocarcinoma

The prognosis of pancreatic adenocarcinoma is dismal. Hence, advances in multidisciplinary treatment strategies, including surgery, are urgently needed. Early recurrence of distant organ metastases suggests that there are occult metastases even in cases with resectable disease. Several randomized controlled trials on adjuvant chemotherapy have been conducted to prolong survival after resection. CONKO-001 study was the first to demonstrate significant improvement in disease-free survival after surgery with gemcitabine administration. The JASPAC-01 study showed the superiority of adjuvant S1 over gemcitabine in survival after resection. Based on the results, adjuvant S1 therapy is the prescribed standard of care in Japan. Recently, the PRODIGE 24/CCTG PA.6 study showed that survival of patients treated with a modified FOLFIRINOX regimen as adjuvant therapy was significantly longer than those treated with adjuvant gemcitabine therapy. Although the evidence from these trials on adjuvant chemotherapy have been the gold-standard treatment for curatively resected and fully recovered patients, resectable disease at diagnosis is not the status, resected disease after curative resection. Currently, neoadjuvant therapy is considered to be a promising alternative to surgery for pancreatic cancer. Although there are many reports regarding neoadjuvant chemoradiotherapy, so far there has been no solid evidence proving the advantage of this strategy versus standard up-front surgery. Newly obtained results from the Prep-02/JSAP05 randomized phase II/III study, comparing neoadjuvant therapy with up-front surgery, revealed significant improvement in overall survival with neoadjuvant chemotherapy by intention-to-treat analysis. Thus, neoadjuvant intervention might become a new standard strategy in cases undergoing planned resection for pancreatic cancer.