Margin Status Impacts Survival after Pancreaticoduodenectomy but Negative Margins Should Not be Pursued

Abstract

Negative margins are the goal with pancreaticoduodenectomy for pancreatic adenocarcinoma. Thereby, margins are assessed intraoperatively with frozen section analysis and negative margins are pursued. This study was undertaken to determine the impact of margin status with pancreaticoduodenectomy for pancreatic adenocarcinoma and the value of extending resections to achieve negative margins. The intraoperative frozen section analysis and final margins for 448 patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma were assessed and their impact on survival was determined. Median data are presented. Two hundred ninety-eight (67%) patients had negative margins (R0), an additional 110 (25%) patients had microscopically positive and macroscopically negative margins (R1), and an additional 40 (9%) patients had initially positive microscopic margins, which became negative with further resection (R1 å R0). R0 resections were more likely to have smaller tumors, earlier T grade, earlier N grade, lower American Joint Committee on Cancer stage, and less frequent extrapancreatic extension ( P ≤ 0.03 for each). Survival was better with R0 resections than R1 resections (20 vs 12 months, P < 0.001); extending resections to achieve negative margins (i.e., R1 ! R0) did not improve survival beyond R1 resections (14 vs 12 months, P = 0.19). Survival after pancreaticoduodenectomy is disappointing. Patients with initial negative margins do best. Positive microscopic margins reflect more aggressive tumor-specific factors and lead to abbreviated survival even with extended resections to achieve negative margins (i.e., R1 ! R0). With an initial positive margin, pursuing negative margins does not improve survival and, thereby, negative margins should not be “chased.”

Predicting early mortality in resectable pancreatic adenocarcinoma: A cohort study

“…For overall survival, adverse prognostic factors were surgical resection margin status and elevated BUN or bilirubin at baseline. The surgical resection margin is most likely associated with inferior long‐term outcomes, although data are controversial . A possible reason for these discrepant findings is that the surgical resection margin status is an amalgam of various factors, such as patient selection for surgery, surgical volume and technique of pathologic assessment, disease biology, and the effect of any preoperative chemotherapy or radiotherapy.…”

“…These patients may not benefit from the current standard of care but to our knowledge little is known regarding how best to identify such patients at high risk of early mortality. Surgical resection margin has been shown to be associated with survival outcomes, although there are some contradictory reports owing to nonstandardized pathologic margin assessment . CA 19‐9 is another marker reported to have varying associations with survival .…”

Neoadjuvant therapy affects margins and margins affect all: perioperative and survival outcomes in resected pancreatic adenocarcinoma

“…28,38,39 Pursuit of negative margins after positive intraoperative frozen-section analysis has been shown to be associated with worse survival than negative margins on initial intraoperative frozen sections. 40,41 In addition, comparability of studies on resection margin status is often plagued by frequent underreporting of microscopic margin involvement due to inconsistent pathologic review practices. 42 Neoadjuvant therapy has also shown to alter the consistency of the pancreas, which may impact pathologic evaluation of tumor cells at the circumferential margin.…”

Pathologic assessment of gastrointestinal tract and pancreatic carcinoma after neoadjuvant therapy

“…109 Microscopically positive margins (R1 resection) are associated with reduced survival in patients with pancreatic ductal adenocarcinoma. [120][121][122][123] The reported rate of R1 resections for locally advanced pancreatic ductal adenocarcinoma following neoadjuvant therapy varies widely from 0 to 51%. [124][125][126] A relatively recent meta-analysis of 111 studies found that of patients who were considered non-resectable prior to neoadjuvant therapy, 33.2% eventually underwent surgical resection with an R0 rate of 79.2%.…”