Neoadjuvant Therapy for Resectable and Borderline Resectable Pancreatic Cancer

Susan Tsai, Kathleen K. Christians, Ben George, Paul Ritch, Kiyoko Oshima, Parag Tolat, Ashley Krepline, Beth A. Erickson, Douglas B. Evans
2016 Journal of Cancer Therapy  
The majority of patients with localized pancreatic cancer (PC) who undergo surgery followed by adjuvant therapy will develop metastatic disease, suggesting that surgery alone is not sufficient for cure and micrometastases are present even when are not clinically detected. As such, the delivery of early systemic therapy may be a rational alternative to a surgery-first approach, in an effort to provide oncologic therapies which are commensurate with the disease stage, and improve surgical
more » ... ve surgical selection. This review details the rationale for a neoadjuvant approach to localized PC and provides specific recommendations for both pretreatment staging and treatment sequencing for patients with resectable and borderline resectable PC. Keywords Pancreas Cancer, Neoadjuvant Therapy, Review * Corresponding author. S. Tsai et al. 25 However, in contrast to many other solid tumors, pancreatic cancer is now recognized as a systemic disease which is metastatic at diagnosis in almost all patients (albeit radiographically occult in many) [2] . Despite this reality, a surgery-first treatment strategy has remained favored by many oncologists and most surgeons because it can be associated with an immediate complete response (even if not durable) and intense multimodality therapy, especially if given in the neoadjuvant setting, is often difficult to deliver. Although a randomized trial comparing neoadjuvant therapy to surgery first for localized pancreatic cancer has not been attempted in the United States, it has been tried in Europe and failed due to poor accrual [3] [4] . It is unlikely that such a trial will be attempted in the future as such visible differences in treatment sequencing make equipoise hard to achieve for physicians and their bias usually is perceived by the attentive patient. One of the first papers reporting the results of a prospective trial of preoperative (neoadjuvant) chemoradiation (cXRT) for patients with localized pancreatic cancer was published by Evans, Rich and colleagues in 1992 [5]. This trial evolved from the following clinical observations: (1) a subset of patients who underwent pancreaticoduodenectomy (PD) first experienced early postoperative disease recurrence. Such patients, if treated with a neoadjuvant approach, may be identified at the time of post-treatment re-staging prior to surgery, and thereby be spared the morbidity and mortality of an ineffective operation, (2) neoadjuvant cXRT may be more effective than adjuvant cXRT and may prevent/decrease both local and regional (peritoneal cavity) recurrences and (3) the delivery of adjuvant therapy after a large operation (such as PD) was difficult, and often was not given/completed. In the future, as systemic therapies improve, a surgery-first approach will prevent many patients from receiving effective systemic therapies. When this trial was developed over two decades ago, the hope was that a neoadjuvant treatment strategy would avoid operation in those patients with aggressive tumor biology for whom surgery would be ineffective, and as well, allow us the opportunity to develop the infrastructure needed to deliver more intensive combined modality therapy, including techniques for pretreatment biopsy, biliary decompression, and supportive care. Figure 1 is a contemporary consecutive series of patients from our institution treated with neoadjuvant therapy for resectable or borderline resectable pancreatic cancer. Those patients found to have disease progression at the time of post-treatment/preoperative re-staging (or at the time of laparoscopy/laparotomy) did not undergo resection (Figure 1, curve B) ; those with stable or responding disease after induction therapy completed all intended therapy, including successful surgical resection of their primary pancreatic tumor (Figure 1 , curve A). In the 1990s, when we began to explore novel treatment sequencing in a neoadjuvant fashion, we were focused on preventing surgery in those who were destined to develop early disease progression. Many of the chal-
doi:10.4236/jct.2016.71004 fatcat:gv66pob7vjb6ne6pym5cewqmwe