Stage III Pancreatic Cancer
Patients with stage III pancreatic cancer have tumors that are technically unresectable because of local vessel impingement or invasion by tumor. These patients may benefit from palliation of biliary obstruction by endoscopic, surgical, or radiological means. A significant proportion of patients approaching one-third of all patients with pancreatic cancer will present with stage III or locally advanced disease. While stage III and stage IV pancreatic cancer are both incurable, the natural history of stage III (locally advanced) disease may be different than it is for stage IV disease. An autopsy series demonstrated that 30% of patients presenting with stage III disease died without evidence of distant metastases.[Level of evidence: 1iiA] Therefore, investigators have struggled with the question of whether chemoradiation for patients presenting with stage III disease is worthwhile.
Table 5. Randomized Studies in Stage III Pancreatic Cancer: Median Survival
|Trial||Regimen||Chemoradiation||Radiation Alone||Chemotherapy Alone||P Value|
|5 FU = 5-fluorouracil; ECOG = Eastern Cooperative Oncology Group; FFCD = Fédération Francophone de Cancérologie Digestive; GEM = gemcitabine; GITSG = Gastrointestinal Tumor Study Group; Gy = gray (unit of absorbed radiation of ionizing radiation);P value = probability value; XRT = x-ray or radiation therapy.|
|GITSG||Radiation alone vs. 5-FU/60 Gy XRT||40 weeks||20 weeks|| ||<.01|
|ECOG||Radiation vs. 5-FU, mitomycin C/59 Gy XRT||8.4 months||7.1 months|| ||.16|
|FFCD||GEM vs. GEM, cisplatin, 60 Gy XRT||8.6 months|| ||13 months||.03|
|ECOG||GEM vs. GEM/50.4 Gy XRT||11.1 months|| ||9.2 months||.017|
Prior to 2000, several phase III trials evaluated combined modality therapy versus radiation therapy alone. Prior to the use of gemcitabine for patients with locally advanced or metastatic pancreatic cancer, investigators from the GITSG randomly assigned 106 patients with locally advanced pancreatic adenocarcinoma to receive external beam radiation therapy (EBRT) (60 Gy) alone or to receive concurrent EBRT (either 40 Gy or 60 Gy) plus bolus fluorouracil (5-FU).[Level of evidence: 1iiA] The study was stopped early when the chemoradiation therapy arms were found to have better efficacy. The 1-year survival was 11% for patients who received EBRT alone compared with 38% for patients who received chemoradiation with 40 Gy and 36% for patients who received chemoradiation with 60 Gy. After an additional 88 patients were enrolled in the combined modality arms, there was a trend toward improved survival with 60 Gy EBRT plus 5-FU, but the difference in time-to-progression and overall survival (OS) was not statistically significant when compared to the 40 Gy arm. In contrast, investigators from the ECOG randomly assigned 114 patients to radiation therapy (59.4 Gy) alone or with concurrent infusional 5-FU (1,000 mg/m2 daily on days 2 through 5 and days 28 through 31) plus mitomycin (10 mg/m2 on day 2) and found no difference in OS between the two groups.