Improved pancreatic survival seen after neoadjuvant therapy and surgery

Last Updated: 2018-04-18

By Will Boggs MD

NEW YORK (Reuters Health) - In highly selected patients with locally advanced pancreatic cancer (LAPC), surgical resection after neoadjuvant therapy is feasible and associated with longer overall survival, researchers report.

"The main message we need to convey is that with the development of advanced systemic treatments (chemotherapy and radiotherapy) patients with non-metastatic LAPC have increased chance for surgery and, therefore, increased chance for improved survival," said Dr. Georgios Gemenetzis from Johns Hopkins University School of Medicine in Baltimore, Maryland.

"No patient with localized pancreatic cancer should be treated with a palliative approach in mind," he told Reuters Health by email.

LAPC, which accounts for 30% of all newly diagnosed pancreatic cancers, is generally considered to be surgically unresectable because of local involvement of adjacent vessels. Current guidelines recommend nonoperative treatment for patients with good performance status.

Retrospective studies have suggested that resection after induction chemotherapy could be curative in patients with LAPC. Dr. Gemenetzis and colleagues analyzed retrospective data on 415 patients with LAPC to see if surgical resection after neoadjuvant therapy was indeed associated with improved survival compared with aggressive nonoperative management.

Surgical exploration was offered to 13 patients based on tumor response to neoadjuvant therapy and to 103 patients without signs of local disease progression or metastases after completion of at least four months of neoadjuvant therapy.

Resection of the primary tumor was achieved in 84 patients (20% of all LAPC patients and 72% of those eligible for exploration). Resection was aborted intraoperatively in 12 patients due to occult abdominal metastatic disease and in 20 patients due to local extension of the tumor.

Resection margins were negative for tumor (R0) in 89% of cases, the researchers report in Annals of Surgery, online March 28.

After resection, 40 patients eventually developed disease recurrence, most commonly local recurrence (13 patients) or distant liver metastases (nine patients).

Median survival from the time of diagnosis was 35.3 months for the resected group and 16.2 months for the 331 patients treated only with chemotherapy and radiation therapy.

Overall survival rates at one and three years were significantly higher in the resected group (96% and 50%, respectively) than in the non-resected group (74% and 11%, respectively).

"Even though only 1 out of 5 patients will eventually undergo successful surgery, our team was excited to see that these patients had comparable survival after neoadjuvant therapy and surgery, to patients with initially resectable disease - a significant improvement in their survival," Dr. Gemenetzis said.

"At the moment we cannot identify with scientific certainty in which LAPC patients their status will shift from unresectable to potentially resectable," he said. "We can, however, say that LAPC patients who undergo neoadjuvant therapy need to be followed closely and assessed repeatedly within a multidisciplinary setting in high-volume centers for pancreatic surgery to identify as accurately as possible those who can be taken to surgery."

Dr. Marc Besselink from Academic Medical Center in Amsterdam, the Netherlands, who studies pancreatic cancer and its treatment, told Reuters Health by email, "This study confirms earlier smaller studies, including ours, that 20% of patients with LAPC can undergo a resection following several months of chemotherapy with a very promising 35 months survival. This study also clearly demonstrates the problem of selecting LAPC patients for surgical exploration."

"The Hopkins group, ours in Amsterdam, and several other groups in the world are working on new methods of better selecting patients for resection; this includes biomarker response (e.g., CA19.9), serial MRI and PET scanning, and intraoperative ultrasound," he said. "This will improve our practice immensely, but all these methods are being developed and require further study and experienced hands and (interventional) radiologists."

"These findings, to me, demonstrate the importance of discussing all patients with LAPC with a highly experienced pancreatic-cancer team," Dr. Besselink said. "We need to move towards larger networks of hospitals wherein we can guarantee to all patients within the network that their scan will be assessed by experts. We don't want to give 80% patients with LAPC false hope, but we also do not want to miss the 20% of resectable patients."

Dr. Amit Mahipal from Mayo Clinic, in Rochester, Minnesota, recently reviewed the contemporary management of localized respectable pancreatic cancer. He told Reuters Health by email, "Patients with LAPC should be considered for neoadjuvant chemotherapy and radiation therapy in hopes of surgical resection. Neoadjuvant chemotherapy should be considered for 4-6 months. SBRT (stereotactic body radiotherapy) can be used as radiation modality of choice."

"Aggressive neoadjuvant therapy can help in reducing the tumor and making surgery feasible," said Dr. Mahipal, who was not involved in the study.

SOURCE: https://bit.ly/2J2gbrB

Ann Surg 2018.