Neoadjuvant Treatment in Pancreatic Cancer

Abstract:

Neoadjuvant chemoradiation is a logical approach to the treatment of pancreatic cancer given its aggressive course and high likelihood for being metastatic at the time of diagnosis. A surgery-last (neoadjuvant) approach may confer the advantages of decreased toxicity (patients are not in the postoperative recovery phase of their illness) and increased efficacy (systemic therapy not delayed) as compared with adjuvant treatment given following a large operation. Further, because patients with progressive disease may be identified prior to operation, neoadjuvant therapy offers the benefit of improved patient selection for pancreaticoduodenectomy (PD). In patients with borderline resectable disease in whom surgery may be possible (but is not an attractive initial option), neoadjuvant therapy may increase the chance of a margin negative resection by sterilizing the tumor cells at the periphery of the tumor even in the absence of a partial or complete radiographic response. The critical components of successful neoadjuvant treatment sequencing for pancreatic cancer include a clear definition of resectability (and unresectability) based on accurate radiographic staging, the ability to achieve a tissue diagnosis of cancer, and means to safely decompress the biliary system when necessary.

There have been at least 13 prospective trials evaluating the role of neoadjuvant treatment for localized (T1-T3) pancreatic adenocarcinoma. Two of the largest and most recent trials evaluated gemcitabine, with or without cisplatin, and rapid fraction radiation therapy; 66–74% of patients ultimately underwent pancreaticoduodenectomy. Positive resection margins were uncommon and the median survival for patients who completed all treatment to include resection of the primary tumor was 31–34 months. This encouraging data has provided initial evidence in support of a neoadjuvant gemcitabine-based treatment strategy for patients with localized, potentially resectable pancreatic adenocarcinoma.

Patients with borderline resectable disease are particularly well suited to neoadjuvant treatment sequencing, although no standardized treatment strategy has been identified. When the operation is more difficult and potentially of even higher risk, and the risk for recurrence is also increased, a surgery last strategy is appealing in order to exclude those patients from surgery who are demonstrated to have progressive disease or evolving medical comorbidities which a neoadjuvant treatment strategy may expose. Many studies have been done in patients with locally advanced disease but only recently has the category of borderline resectable disease been accurately defined. The value of accurate pretreatment staging and multidisciplinary care is now becoming apparent to clinicians of all specialties. However, for this to be possible, all members of the multidisciplinary team must agree on the definitions used to stage patients radiographically because treatment is stage specific.