With a five-year survival rate of 13%, pancreatic cancer is among the deadliest cancers. The high mortality rate necessitates dedication and innovation to improve patient treatment outcomes. Because Stanford is the highest volume medical center for pancreatic cancer operations in California, the gastrointestinal (GI) cancer team members—which includes surgeons, medical oncologists, radiation oncologists, interventional radiologists, dietitians, and nurses—have broad experience in managing every stage of this disease.

Stanford Cancer Institute member Brendan Visser, MD, medical director of the Stanford Gastrointestinal Cancer Care Program and section chief of Hepato-Pancreato-Biliary (HPB) in the Stanford Department of Surgery, spoke about the challenges inherent in pancreatic cancer treatment and how patient outcomes can be improved.

“It’s a field that is technically and intellectually challenging. The patients have such tough cancers that when you have a good result, it is incredibly rewarding. When you’re fighting against very long odds, the victories are that much more fulfilling.” 

Late diagnosis

There are no screening tests to detect pancreatic cancer when it’s in the early stages, so the disease is often diagnosed at later stages than many other cancers. Pancreatic cancer is either found by chance or when patients become symptomatic. The most common symptom is obstructive jaundice, which occurs when the tumor is close enough to the bile duct that it impinges on the bile flow and causes the patient’s skin to turn yellow. 

Visser says, “It’s geographically dependent, so if you take the same tumor and move it a centimeter to the left in the pancreas as its starting point, it may get that much bigger before it ends up pushing on the bile duct. Tumors have typically been there for months before a patient develops symptoms.” 

Because pancreatic cancer tends to be found at later stages, patients often have metastatic disease at the time of diagnosis.

Tough biology

Pancreatic cancers have a “tough biology,” meaning they are more aggressive than the bulk of GI cancers. They grow faster and are more resistant to systemic therapy interventions, even when diagnosed early.

Visser says, “Pancreatic cancer has always been a notoriously chemoresistant disease. With some cancers, like colon cancer, chemotherapy is very effective, and the majority of patients with metastatic colon cancer will respond to chemotherapy. A good percentage of pancreatic cancer patients will respond to chemotherapy, but it remains a much smaller percentage compared to other patients.”

Pancreatic cancer consists mostly of fibroblasts or scar tissue within nests of cancer cells in the middle of those big fields of scar tissue, so it’s harder to get chemotherapy agents into those cells to impact their cell cycling than it is for other cancers. Additionally, pancreatic cancer cells are hypoperfused, which is characterized by a lack of oxygen and nutrients reaching the tumor cells. This leads to a harsh environment where tumor cells adapt and become more aggressive, and it affects the delivery of therapeutic agents, making treatment less effective. 

Immunotherapy, which relies on making cancer cell antigens more visible to make it easier for immune cells to find and destroy the cancer, is also less effective because pancreatic cancer antigens are trickier to target.

Pancreatic cancer surgery

Patients with localized (or non-metastatic) disease are potentially candidates for tumor resection (or surgical removal), and pancreatic surgeons typically are present at every step of the journey. 

“As an HPB surgeon, you help guide the patient and their family with all elements of pancreas cancer, and you’re in it from the moment of their diagnosis through their chemotherapy, surgery, recovery, and then back to chemo and then on to surveillance imaging.” 

Pancreatic cancer surgery for tumors in the head of the gland is complex. It requires removing portions of the pancreas, duodenum, bile duct, and gallbladder and then reassembling the bowel continuity. Because the operation requires three new surgical connections to be completed, the surgery has a significant complication rate and was previously notorious for its significant mortality rate.  As such, a big step in pancreatic cancer treatment has been reducing the risk and morbidity of these operations through minimally invasive approaches, which involve small incisions rather than the large incisions in traditional pancreatic cancer surgery. The minimally invasive approach has become feasible in many more cases due to the growing application of robotic surgery, which offers tremendous precision for the surgeon and an easier recovery for the patient.

Visser says there is a growing toolbox for advanced tumors that has resulted from incremental knowledge gained from surgeons' ability to innovate their approach due to increased patient volume. Surgeons can now operate on non-metastatic, locally advanced tumors, meaning the tumor has grown beyond the initial organ but has not yet spread to other parts of the body. Locally advanced pancreatic tumors are typically wrapped around the blood vessels to the bowel. These surgeries require complex blood vessel reconstruction, which would’ve been unthinkable when he was a resident in the early 2000s. Additionally, current technology allows for 3D operative planning to facilitate better visualization and surgical planning for the most complex tumors.

“In the last decade, the safety of pancreatic cancer surgery has dramatically improved, and our ability to do it in a less invasive way has also improved. This is critical because pancreas surgery still remains a big survival changer for patients who can get surgery, so making the operation less morbid and having a faster recovery is a really meaningful advance, and this is continuing to get better.”

Advancing therapies

Even though pancreatic cancer is hard to treat with systemic therapies, promising therapies are on the horizon. Visser notes there hasn’t been much past success in targeting the KRAS mutation, which is present in the majority of pancreatic cancers. However, there is now early evidence suggesting that recently developed KRAS inhibitors will be effective at turning off the mutation, which will be a game-changer for pancreatic cancer treatment.

Visser points to Stanford surgeons and Stanford Cancer Institute members Michael Longaker, MD, and Dan Delitto, MD, PhD, FACS, as forging research breakthroughs. Longaker is a plastic surgeon whose lab collaborates with scientists from diverse disciplines to further our understanding of fibrosis in different disease states. Because pancreatic cancer is an unusually fibrotic tumor, the group is doing important work that will inform how the cancer reacts to systemic therapies. Delitto’s work in reprogramming the pancreatic cancer microenvironment is expected to open the door to effective immune modulating therapies, including vaccine approaches and immune checkpoint inhibitors. These advances will likely have a positive impact on the field and help create strategies that are adopted into clinical medicine. 

Additionally, chemotherapy has become more successful for pancreatic cancer patients because they can now safely give a more aggressive regimen or an aggressive combination of chemotherapy agents. Visser notes that while chemotherapy hasn’t changed dramatically in the last decade, it is still substantially better than in the early 2000s when he was a resident.

“There was a time when people imagined that surgeons would fade out as we developed better medical therapies for these cancers. We’d be doing less because we’d treat more of these cancers with medical systemic therapies alone. In fact, it’s the opposite. As we get better systemic therapy, we can get more patients to surgery because we’ve been able to downstage their disease and make them good surgical candidates, so we actually do more surgery than we ever have done before.” 

Care fragmentation

Care fragmentation occurs when a cancer patient receives different treatments at various facilities, which can lead to less optimal outcomes. Geographic barriers between facilities can lead to inadequate communication between providers, resulting in care delays and poor care decisions. The impact of care fragmentation is a key area of investigation by Visser.

“The care patients receive is less ordered, and there are more chances for things to fall between the cracks or decisions to be made that are not holistically looking at all elements and options. To the degree that geography is a limitation, we need better systems for streamlining communication among centers that are looking after a patient. Right now, our medical record systems and communication systems, for HIPAA-related reasons, remain somewhat siloed.”

Visser believes fixing these systemic holes can be achieved by steering patients to high-volume and high-expertise medical centers. His team’s research demonstrates these centers are more likely to follow National Comprehensive Cancer Network guidelines to optimize patient outcomes. To receive care at these centers, patients and providers need to identify centers of excellence, and patients may have to travel. More than anything, Visser says that payers should prioritize patient outcomes and support centralization of services to bridge the gaps in care fragmentation. 

Bridging care fragmentation can lead to better safety and efficacy of care because better-informed decisions are being made by all providers involved in a patient’s care. Like more advanced, safer surgical techniques and effective systemic therapies, it’s one of the pieces of the puzzle needed to improve pancreatic cancer outcomes across the population.

By Kaite Shumake
June 2025