Improving care of patients with pancreatic cancer
Effective chemotherapy, improved radiation and advanced surgical techniques form the basis of a multimodal team approach that has yielded promising results.
Despite improvements in overall survival for most cancers, survival for patients with pancreatic cancer has remained dismally low for decades. For all stages of pancreatic cancer, the one- and five-year survival rates are 20 percent and 4 percent, respectively.
The main cause is late detection and tumor spread, which affects 50 percent of patients at diagnosis. Other tumors are unresectable because of vascular encasement. Only 20 percent of patients have tumors confined to the pancreas at diagnosis.
According to Mark J. Truty, M.D., M.S., a surgical oncologist at Mayo Clinic in Rochester, Minnesota, surgery is the one aspect of pancreatic cancer care that has improved significantly over time. But the technical refinements and advances in postoperative care that reduced complications and operative mortality have not improved survival — patients with resectable cancers have an average survival of just 18 to 20 months, with overall five-year survival rates of 20 to 25 percent.
"We can do complex cancer operations, including advanced reconstructions of veins and arteries, quite safely, but with no essential impact on long-term outcomes. For every technical improvement developed, there is decreasing incremental improvement in overall survival," Dr. Truty explains. "As the majority of patients develop metastatic disease after curative operations, it is painfully obvious that most probably have undetectable metastases at the time of surgery."
To address unseen cancer cells and improve long-term outcomes, Mayo Clinic recently began using the combination regimen FOLFIRINOX for neoadjuvant therapy. In a recent phase III trial for patients with metastatic pancreatic cancer, FOLFIRINOX had a more than threefold greater response rate compared with gemcitabine.
Dr. Truty, too, is seeing significant response rates in patients — some with borderline or locally advanced tumors. Those patients also receive radiation before surgery to avoid a positive margin.
This strategy has many benefits. It identifies patients who have chemotherapy-resistant micrometastases at diagnosis, thus saving them from unnecessary surgery. It downstages cancers that are otherwise inoperable or at risk of having positive margins. And it allows patients to receive treatment to eradicate known metastatic cancer cells before surgery and gives them time to physically prepare for a major operation.
"We are looking for no metastases, regression or nonprogression of the primary tumor, a biomarker response, and improvement in clinical symptoms. Patients who fulfill these criteria and go to surgery do markedly better than average," he says. "Margin rates are improved, lymph node involvement is less, and in many cases, there is very little tumor left."
For these patients, aggressive surgery with multiple vessel reconstruction is worth it, Dr. Truty says, because chances of a positive outcome are much improved. "Before, it was a game of chance. Now, we are trying to strategize and perform the right operation on the right patients. We stack the odds for our patients and offer hope."
He adds, "We offer a protocol-based approach. Although each patient and cancer is different, we limit variability to maximize outcome. That helps us push the envelope surgically, to take previously unresectable patients and get them through complex procedures. This is a really exciting time in pancreatic cancer surgery. We now have effective chemotherapy, improved radiation and advanced surgical techniques for a multimodality team approach."
He notes that patients work with a care team that includes surgeons, oncologists, dietitians and psychologists. The short-term data is very promising.
"We are trying to slow the cancer down and find the right time to intervene surgically," he says. "Before, we were basically trying to catch running water with our hands. With this new approach, we are trying to slow the flow from the faucet and in many cases actually freezing the water to make cancer easier to treat."