IN2008,APPROXIMATELY37 000PATIENTSWILLBEDIAGNOSED with pancreatic adenocarcinoma in the United States, and most of these patients will succumb to this disease within thefirstyearfollowingdiagnosis.Onlyapproximately7400 patients will have localized cancer, usually involving the head of the pancreas, and are candidates for surgery if the tumor is resectable, asdefinedby theabsenceofvascular involvement. Such patients are candidates for complete resection of the primary cancer. The prognostic significance of an incomplete resection is well-defined (ie, the survival duration of those who undergoanincomplete[R1]resectionisonaverageshorterthan thatofpatientsachievingacomplete[R0]resectionandinsome series is no different than the survival of patients with locally advanced stage III disease who receive chemoradiation without surgery, chemotherapy, or both). With optimal patient selection, improvedsurgicaltechniques,andmodernperioperativecare,manypatientswhoundergopancreatic resectionwill recoveradequately tobecomecandidates forpostoperativeadjuvanttherapyandthis,coupledwiththehighfrequencyofcancer recurrence followingsurgery,providesa strong impetus to offer such therapy to patients. The value of therapy following surgical resection of pancreatic adenocarcinoma has been controversial since 1985 following the publication of the first results of the Gastrointestinal Tumor Study Group’s (GITSG) underpowered, longaccruing trial. That study, involving 43 randomized and analyzed patients, demonstrated a survival of 21 months for patients treated with fluorouracil-based chemoradiation and prolonged treatment with systemic fluorouracil compared with an 11-month survival for patients treated with surgery alone. At that time, the rationale for chemoradiation was that the recurrence pattern of resected pancreatic adenocarcinoma involved local recurrences in the pancreatic bed and metastatic failures involving the liver and peritoneal surfaces necessitating protracted administration of systemic fluorouracil. Subsequently, 6 additional randomized controlled trials have been published. The most important of these are the European Study Group for Pancreatic Cancer (ESPAC-1) trial published in 2004 and the Charite Onkologie (CONKO-001) trial published in 2007. In ESPAC-1, patients who were treated with fluorouracil alone (median survival, 21.6 months) or fluorouracil and fluorouracil-based chemoradiation (median survival, 19.9 months) had improved survival compared with patients treated with surgery alone (median survival, 16.9 months). In CONKO-001, patients who were treated with postoperative gemcitabine experienced a median diseasefree survival of 13.4 months vs 6.9 months for patients treated with surgery alone. This difference was statistically significant (P .001, log-rank test) yet there was no difference in overall survival between the gemcitabine-treated group (median survival, 22.1 months) and the surgery-alone control group (median survival, 20.2 months). Now adding to these data are the results of the US Gastrointestinal Intergroup trial RTOG 97-04 led by the Radiation Therapy Oncology Group (RTOG) reported in this issue of JAMA. Unlike the other trials, this study did not seek to determinewhetherpostoperative therapywasbetter thansurgery alone,butexaminedwhethersurvivalcouldbeextendedbysubstitutinggemcitabineforfluorouraciladministeredsystemically before and after fluorouracil-based radiation. Gemcitabine is a nucleoside analog with activity in advanced pancreatic cancer greater than that of fluorouracil. The strategy of combining both local-regional and systemic therapy persists because despite improvements in preoperative staging, many investigators are still concerned about local as well as distant failure. Judging from the 34% overall rate of margin-positive resectionsdocumented in theRTOGtrial, thisconcernmaybewellfounded.However, intheESPAC-1trial andtheCONKOtrial, theratesofpositive resectionmarginswereonly18%and17%, respectively, and themediansurvival for thesurgery-alonepatients inthesetrialswere16.9monthsand20.1months, respectively. These results are comparable with the results in RTOG achieved by treatment with postoperative chemotherapy and chemoradiation.Theseinvestigatorshavenotdevelopedpathological quality control to the point at which clinicians can be confident that a microscopically positive margin (R1) can be accurately differentiated from a grossly incomplete resection (R2); more attention to the pathological details in future trials is warranted. The magnitude of this problem for RTOG is reflected in the 25% of pathology reports that provided no information regarding the status of the surgical margins.