Survival advantage of combined chemoradiotherapy compared with resection as the initial treatment of patients with regional pancreatic carcinoma. An outcomes trial.
BACKGROUND
Resection of pancreatic carcinoma is resource-intensive with a limited impact on survival. Chemotherapy and/or radiotherapy (RT) have been shown to be effective palliation. To examine whether preoperative chemoradiotherapy as the initial treatment improves survival for patients with a regional pancreatic adenocarcinoma with a minimal chance of being resected successfully, an outcomes trial was conducted.


METHODS
Patients with radiologically regional tumors were staged by laparotomy and/or computed tomography followed by endoscopic ultrasonography, angiography, and/or laparoscopy. Those with locally invasive, unresectable, regional pancreatic adenocarcinoma initially were treated with simultaneous split-course RT plus 5-fluorouracil, streptozotocin, and cisplatin (RT-FSP) followed by selective surgery (Group 1). Patients determined to have a resectable tumor initially underwent resection without preoperative chemoradiotherapy, with or without postoperative chemoradiotherapy (Group 2).


RESULTS
Over 8 years 159 patients presenting with nonmetastatic pancreatic adenocarcinoma were administered RT-FSP or underwent surgery for resection. Group 1, comprised of 68 patients initially treated with RT-FSP, had a 0% mortality rate within 30 days of entry. In 20 of 30 patients undergoing surgery after RT-FSP, tumors were downstaged and resected. Group 2, comprised of 91 patients who initially underwent successful resection, had a 5% mortality rate within 30 days of entry. Postoperatively, 63 of these patients received chemotherapy with or without RT. The median survival for Group 1 was 23.6 months compared with 14.0 months for Group 2 (P = 0.006) despite more advanced disease cases in Group 1. Survival favored RT-FSP regardless of whether lymph nodes were malignant. The dominant prognostic factor of earlier stage pancreatic carcinoma having an expected survival advantage was reversed by the initial nonoperative treatment.


CONCLUSIONS
Based on a reversal of the expected trend that patients with earlier stage resectable carcinoma (T1,2, N0,1, M0) who undergo removal of their tumors survive longer than patients with more advanced regional disease (T3, N0,1, M0), survival was found to improve significantly for patients reliably staged as having locally invasive, unresectable, nonmetastatic pancreatic adenocarcinoma when initially treated with RT-FSP.
Department of Medicine, Mt. Sinai Medical Center, New York, New York, USA.
H
H
Snady
H
H
Bruckner
A
A
Cooperman
J
J
Paradiso
L
L
Kiefer
D000230:Adenocarcinoma / Q000473:pathology / Q000601:surgery* / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000601:surgery* / Q000628:therapy*; D011879:Radiotherapy Dosage; D013311:Streptozocin / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome
D013311:Streptozocin; D002945:Cisplatin; D005472:Fluorouracil