Extended Preoperative Chemotherapy Allows Pancreatic Cancer Surgery Success

Prolonged preoperative chemotherapy duration may improve the outcome of patients with stage III pancreatic ductal adenocarcinoma

  • Date: 09 Dec 2013
  • Author: Lynda Williams, Senior medwireNews Reporter
  • Topic: Pancreatic Cancer

medwireNews: Prolonged preoperative chemotherapy is key to treatment outcome in patients with locally advanced or borderline resectable (LA/BR) pancreatic ductal adenocarcinoma (PDAC), research suggests.

The study, published in JAMA Surgery, reports a median overall survival rate of 40.1 months, ranging from 22.7 to 65.9 months, for the 49 patients treated for stage III, initially inoperable disease using the protocol at the University of California, Los Angeles Medical Center. And disease-free survival was a median of 23.2 months.

Treatment of patients with LA/BR PDAC is not standardised. With giving up to four cycles of chemotherapy over 4 months before assessing resectability, explain Timothy Donahue and colleagues at the University of California, the 5-year survival of patients with PDAC has been static over the past 10 years, at just 5.8%.

To improve downstaging, the patients in the study underwent a median of 7.1 months of chemotherapy or chemoradiotherapy before pylorus-preserving Whipple surgery or vascular resection. The majority (65%) of patients had arterial, venous or combined involvement and 92% of the tumours were at the pancreatic head.

Downstaging successfully and significantly reduced the median tumour size, from 3.1 cm to 1.7 cm, and significantly reduced serum levels of the tumour marker CA19-9, from 96.3 U/ml to 20.0 U/ml. A histopathological response was achieved in 24 patients and 45.8% of these patients had a complete response with no visible tumour in their excised tissue.

Margin-negative resection was achieved in 85.7% of patients and 75.5% were found to have lymph node-negative disease.

Of note, patients without lymph node metastasis underwent chemotherapy for a longer period than those with lymph node-positive disease (8.2 vs 6.2 months), although this did not reach statistical significance.

“While these results can be explained purely on the basis of selection bias, it is also plausible that the longer duration of chemotherapy was eradicating disease in the [lymph nodes],” Timothy Donahue et al write.

Initial analysis of clinicopathological variables indicated that survival was significantly predicted by loss of expression of the tumour marker SMAD4, histopathological response, perineural invasion, and lymph node status. In multivariate analysis, however, SMAD4 was the only significant Prognostic factor, with a hazard ratio for survival of 9.3.

“Our approach to patients with LA/BR PDAC, which includes prolonged preoperative chemotherapy, is associated with a high incidence of [lymph node]-negative disease and excellent OS,” the team concludes.

“Histopathologic treatment response, [perineural invasion], and SMAD4 status were significantly associated with OS and may help to determine which patients may benefit from additional adjuvant therapy in this select subgroup of patients.”

Reference

Kadera BA, Sunjaya BE, Isacoff WH, et al. Locally Advanced Pancreatic Cancer: Association Between Prolonged Preoperative Treatment and Lymph-Node Negativity and Overall Survival. JAMA Surg 2013 Dec 4. doi: 10.1001/jamasurg.2013.2690. [Epub ahead of print].

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