Neoadjuvant treatment is always justified for small PDAC, especially for clinical T1? - Debate from the position of Pros.

Lecture: Surgical resection offers the best chance for long-term survival, and upfront surgery is the most universally accepted approach for potentially resectable PDAC. But the result is dismal, the median survival of patients undergoing curative pancreatectomy alone is 18 to 20 months, with a 5-year survival rate of 10%. The administration of adjuvant chemotherapy and possibly chemoradiation leads to an improvement in OS relative to pancreatectomy alone. Adjuvant therapy following pancreatectomy therefore currently represents standard of care for patients with resectable PDAC. But, Administration of planned adjuvant chemotherapy may be limited by postoperative complications and early recurrence. Unfortunately, as few as 50% of patients who undergo pancreatectomy nationwide actually receive postoperative therapy. In an effort to overcome these barriers, early delivery of chemotherapy was evaluated as an alternative treatment sequence strategy. So the neoadjuvant therapies have been proposed. Two major hypothetical risks have been pointed out for neoadjuvant chemotherapy (NAC). One is a possible increase in perioperative morbidity and mortality. Second is the possibility that disease may progress and become unresectable during the course of NAC. A nationwide survey suggested that neoadjuvant treatment might not worsen perioperative outcomes or might increase the chance for curative surgery. NAC offers several theoretical advantages over upfront surgery, including early delivery of systemic therapy for almost all patients intended for treatment, high tolerance of multi-agent regimens by patients and a higher negative-margin resection rate, leading to improve OS. A review of select trials for patients with localized PDAC has suggested increased OS, supporting the benefits. Of course to date, there are no prospective data providing the superiority of neoadjuvant strategy over upfront surgery for resectable PDAC. So neoadjuvant treatment is not always justified for small PDAC, up to now. Nevertheless, neoadjuvant treatment can be a practical treatment strategy, particularly for patients at high biological or perioperative risk.