Outcomes Trial Demonstrating That Initial Effective Neoadjuvant Chemoradiotherapy for Cure Is a Viable Alternative to Initial Surgery for Cure for Regional Pancreatic Adenocarcinoma

Abstract

Purpose: To determine through an outcomes trial whether initial laparotomy for possible resection is the only, or even best, chance for cure for regional pancreatic adenocarcinoma (PCa), we compared initial treatment by successful resection to initial treatment with neoadjuvant chemoradiotherapy (CRT) for those found by any reliable staging protocol to have locally invasive unresectable tumor. Methods: 200 reliably staged PCa patients were analyzed as three groups. 159/200 were allocated into two treatment groups based on a staging protocol. CRT-grp1 included 68 with unresectable locally invasive (T3/4) PCa diagnosed initially by only non-operative imaging in 56% and by laparotomy in 44%; all 68 initially received CRT, followed by surgery in selected patients. R-grp2 included 91 with resectable (T1-3) tumor initially resected successfully of all tumor visible; 63/91 (74%) then received postoperative, adjuvant chemo and/or radiotherapy. Due to contraindications/refusal of other treatments, a third group (NoRx-grp3) of 41 with regional PCa diagnosed by EUS received, as initial therapy, only a stent for biliary obstruction. Results: In CRT-grp1 patients, CT scan showed 39/68 tumors downstaged to resectable after CRT. EUS found 24% of these not resectable. 20/68 (29%) had resection after CRT. For R-grp2, accuracy of EUS prediction of vascular invasion was 98% based on pathology. Median survival: 22.8 mo for CRT-grp1 with 8 disease-free 5yr survivors vs. 14.1 mo for R-grp-2 with 2 disease-free 5yr survivors (p=0.005) despite the initially more advanced disease in CRT-grp1 patients. For the 41 NoRx-grp3 patients, median survival was 8.4 mo with no 5yr survivors (p=0.0001); 5.9 mo for the 58% with unresectable T3/4 tumor on EUS, and 11.6 mo for the 42% with resectable T1-3 tumor on EUS (p=0.0002). One yr survival rates for CRT-grp1, R-grp2 and NoRx-grp3 were 78%, 57% and 22%, respectively; 2yr survival rates were 44%, 31%, and 2%, respectively. Mean follow-up for patients alive was >6 yrs. Conclusions: For advanced, unresectable (T:3/4;N:0,1;M:0) PCa treated with initial CRT and later resection of downstaged tumor when possible, the 12% (8/68) cure rate was significantly greater than the 2% (2/91) for earlier stage (T:1-3;N:0,1;M:0) initially resected PCa. Accurate EUS maximizes the benefit of surgery for PCa. When reliable non-operative staging reveals minimal chance of successful tumor resection, survival improves significantly with initial CRT.