gms | German Medical Science

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by low rates of resectability and high rates of local recurrence or distal metastases after curative resection due to early spread of tumor cells around peripancreatic nerves and vessels. Studies that analyzed the impact of margin/resection (R0/R1) status on overall survival reported on conflicting results, largely due to geographic differences in the definition margin status.

Therefore, in the present meta-analysis we investigated the impact of the resection status on survival of PDAC patients after curative resection within the last 10 years.

Additionally the consecutive resected PDAC patients between 2007 and 2014 at our department were analyzed for prognostic factors including the R0/R1 status.

Materials and methods: Pubmed, Embase and Cochrane databases were screened for the search term

((pancreaticoduodenectomy or pancreatectomy or pancreaticoduodenectomies or duodenopancreatectomy or duodenopancreatectomies or left resection or distal resection) and (resection margin or resection margins or R1 or R0 or negative margin or positive margin or negative margins or positive margins or prognostic factors or prognosis or prognostic factor or survival) and (Pancreatic Neoplasms or pancreas cancer or pancreas cancers or pancreas neoplasm or pancreas neoplasms or pancreas carcinoma or pancreas tumor or pancreas tumors or pancreas tumour or pancreas tumours or pancreatic cancer or PDAC or Ductal Adenocarcinoma or pancreatic Carcinoma) and (operation or operations or operative therapy or operative therapies or surgery or surgeries or resection or resections)) not IPMN not neuroendocrine not laparoscopic not endoscopic not hepatectomy not gastric cancer not renal cell carcinoma not cystic lesions not chronic pancreatitis.

1854 articles meeting the predefined criteria were critically analyzed on relevance and the meta-analysis was performed by pooling only 86 studies that reported univariate and/or multivariate hazard ratios/HR.

From a total of 324 resected patients with PDAC 48 were excluded due to exclusion criteria (perioperative death, preoperative metastases, R2- and arterial resections and neoadjuvant treated patients). 276 patients were analyzed for prognostic factors.

Results: After elimination of studies that lacked PDAC-specific survival rates, a total of 86 studies that analyzed the correlation between R0/R1 status and PDAC-associated survival were included in the meta-analysis. The pooled HR of the multivariate analysis showed a marked impact of resection status on PDAC-specific survival (HR: 1.47; CI 1.42-1.53).

Also in the clinical cohort R1 was also an independent prognostic factor (HR 1.7; CI 1.2-2.4) in addition to N status and differentiation. Furthermore R1-resections were associated with higher local recurrence rates (p=0.03). In a subset analysis of R0-resected patients, there was a significant survival advantage for patients with a negative circumferential resection margin (CRM; p=0.05).

Conclusion: Despite intercontinental discrepancies in the definition of the circumferential resection margins, microscopically clear tumor margins are associated with a favorable overall survival after curative resection for PDAC.