Chemotherapy is a useful treatment to try to get systemic control in pancreatic cancer. Currently, however, chemotherapy is mostly administered in patients whose tumors are more difficult to remove surgically because of where they are in the anatomy.
New research by University of Colorado Cancer Center member Marco Del Chiaro, MD, PhD, one of the world’s foremost researchers on pancreatic cancer, finds that even in patients whose pancreatic cancer tumors are easily resectable, there may be a benefit to administering chemotherapy prior to surgery.
“We used the National Cancer Database to look into what we call primary resectable pancreatic cancer, and in this category of patient, we analyzed retrospectively the outcomes in the ones who received preoperative chemotherapy versus the ones that went directly to surgery,” says Del Chiaro, professor and chief of surgical oncology in the CU School of Medicine. “We observed that there was an advantage in survival of the patient who received preoperative chemotherapy, even in this primary resectable category. The paper supports the idea that biology is more important than anatomy, and probably chemotherapy should be administered to everyone.”
Published in May 2023 in the journal Annals of Surgery, the paper — whose other authors include CU Cancer Center member Anna Gleisner, MD, PhD, and CU Cancer Center Director Richard Schulick, MD, MBA — looked at 5,216 patients with primary resectable tumors who were treated between 2010 and 2017. Four-thousand and forty-one of those patients were treated with upfront surgery, and 1,175 were treated with neoadjuvant chemotherapy, or chemotherapy administered prior to surgery. The study also looked at whether patients received multiagent neoadjuvant chemotherapy — multiple chemotherapy drugs administered together — or one single chemotherapy drug.
“Using a landmark time of six months after diagnosis, patients treated with multiagent neoadjuvant chemotherapy had longer median overall survival, compared to upfront surgery and single-agent neoadjuvant chemotherapy,” the authors wrote in the paper. “Multiagent neoadjuvant chemotherapy was associated with lower mortality rates compared to upfront surgery, whereas single-agent neoadjuvant chemotherapy was not. The findings suggest that multiagent neoadjuvant chemotherapy followed by resection is associated with improved survival compared to upfront surgery.”
“What we observed is that with multiagent neoadjuvant therapy, the median overall survival was 35.8 months,” Del Chiaro says. “With upfront surgery, it was 27.1 months, which is very similar to those who received a single-agent neoadjuvant therapy.”
New treatment guidelines
The research may help to create new guidelines for treating primary resectable pancreatic cancer, which is currently often removed by surgery alone, with no chemotherapy prior to the operation. It may also help to identify patients most likely to benefit from surgery, Del Chiaro says.
“One reason for doing chemotherapy first is to try to exclude the patient that might not benefit from surgery,” he says. “At the end of the day, this is a systemic disease, and people normally die from metastasis. If a patient develops metastasis while they are on chemo, which is possible, then we understand that you don’t respond to chemo, so we don’t do an unnecessary surgery But if they don’t develop metastasis in the months before surgery because the chemo is able to control it, then we know their biology is good, and they have a better chance of survival.”
Del Chiaro also shared that these results are generated by a retrospective study and therefore need to be interpreted carefully. Only after prospective randomized trials, we may have a definitive answer to this question.