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Prolonged preoperative chemotherapy linked to lymph node negativity, improved OS in pancreatic cancer
Prolonged preoperative chemotherapy was associated with increased incidence of lymph node negativity and improved OS in patients with locally advanced or borderline resectable pancreatic ductal adenocarcinoma, according to study results.
Histopathologic treatment response, perineural invasion and SMAD4 status after surgical resection were potential biomarkers that may guide patient selection for adjuvant therapy, researchers found.
Between 1992 and 2011, researchers enrolled 49 patients with stage III pancreatic ductal adenocarcinoma whose tumors were initially deemed unresectable due to vascular involvement.
Patients underwent preoperative chemotherapy for a median of 7.1 months (range, 5.4-9.6).
After this time, 75.5% of patients underwent a pylorus-preserving Whipple operation. Three patients (6.1%) had a vascular resection.
Thirty-seven patients (75.5%) had lymph node-negative disease and 42 (85.7%) had negative margins after surgery.
Among evaluable patients, 45.8% achieved a complete histopathologic response.
Median OS was 40.1 months (range, 22.7-65.9).
Additional analyses indicated that perineural invasion (HR=5.5; P=.007) and histopathologic treatment response (HR=9.0; P=.009) were significantly associated with histopathologic prognosis.
Lymph node involvement was a significant marker of systemic disease (P=.05). Patients with lymph node-negative disease demonstrated a 44.4-month median OS, which was significantly longer than 23.2-month median OS in patients with lymph node-positive disease (P=.04).
OS was also associated with SMAD4 protein loss in tumor cells (P=.01) and microRNA-21 expression in the stroma (P=.05). However, only SMAD4 protein loss remain significantly associated with OS in histopathologic and prognostic multivariate analyses (HR=9.3; P=.004).
“Our approach to patients with locally advanced or borderline resectable pancreatic ductal adenocarcinoma, which includes prolonged preoperative chemotherapy, is associated with a high incidence of lymph node-negative disease and excellent OS,” the researchers wrote. “Histopathologic treatment response, perineural invasion and SMAD4 status were significantly associated with OS and may help determine which patients may benefit from additional adjuvant therapy in this select subgroup of patients.”
Disclosure: The researchers report no relevant financial disclosures.