Pancreatic Cancer Deaths Are Expected to Surpass Colorectal Cancer Deaths

November 22, 2022 - Based on statistics and survival rates, many clinicians have dubbed pancreatic cancer one of the deadliest. According to a publication in the Journal of Cancer Metastasis and Treatment, there were approximately 496,000 pancreatic cancer cases worldwide in 2020. Additionally, in 2020, there were 466,000 pancreatic cancer deaths. Globally, incidence and mortality rates have continued to increase, with some experts anticipating pancreatic cancer to surpass colorectal cancer as the second leading cause of cancer deaths by 2030.

Pancreatic Cancer Overview

Pancreatic cancer, like any cancer, occurs when a DNA mutation leads to uncontrolled cell growth. According to the Mayo Clinic, “most pancreatic cancer begins in the cells that line the ducts of the pancreas. This type of cancer is called pancreatic adenocarcinoma or pancreatic exocrine cancer. Less frequently, cancer can form in the hormone-producing cells or the neuroendocrine cells of the pancreas. These types of cancer are called pancreatic neuroendocrine tumors, islet cell tumors, or pancreatic endocrine cancer.”

The most common kind of pancreatic cancer is pancreatic ductal adenocarcinoma. Unlike other cancers, pancreatic cancer is seldom detected when it is early enough to resect. Often this kind of cancer doesn’t cause symptoms — or severe symptoms — until it has already metastasized.

Risk Factors

While there is no definitive cause for pancreatic cancer, specific comorbidities, genetic factors, and lifestyle decisions may contribute to an increased risk of developing the disease. A history of smoking, diabetes, obesity, chronic pancreatitis, liver cirrhosis, Helicobacter pylori infection, and genetic predisposition may contribute to an increased risk of pancreatic cancer.

StatPearls identifies that men, Black patients, and patients over 55 are more likely to develop pancreatic cancer. North America, Europe, Australia, and New Zealand had the highest incidence rates of pancreatic cancer. Conversely, Middle Africa and South-Central Asia had the lowest incidence rates.

Symptoms

StatPearls notes that approximately 70% of patients with pancreatic adenocarcinoma have painless jaundice due to the obstruction of the common bile duct. Additionally, 90% of patients experience weight loss, and 75% have abdominal pain. Additional symptoms may include fatigue, pruritus, anorexia, distended gallbladder, alcoholic stool, dark urine, recurrent deep vein thrombosis, recent-onset diabetes, elevated liver enzymes, bilirubin levels, amylase, and lipase.

Diagnosis

If a provider suspects pancreatic cancer, they typically begin by conducting imaging tests. Providers may choose to do an ultrasound, CT, MRI, or PET scan. Endoscopic ultrasound may also be used to image the pancreas. This procedure is when an endoscope is inserted through the patient’s mouth, down their esophagus, and into the stomach to image the pancreas internally. Multidetector computed tomography (MDCT) is also used. This type of imaging can typically help determine resectability with 77% accuracy.

A tissue biopsy may also be used to diagnose pancreatic cancer. The tissue is typically collected during an endoscopic ultrasound and examined under a microscope. Fine-needle aspiration may also be used to collect tissue in place of a tissue sample collected during an endoscopic ultrasound.

Finally, blood tests may be used to detect specific tumor markers. According to the Mayo Clinic, “one tumor marker test used in pancreatic cancer is called CA19-9. It may be helpful in understanding how cancer responds to treatment. But the test isn't always reliable because some people with pancreatic cancer don't have elevated CA19-9 levels, making the test less helpful.”

Prognosis and Currently Available Treatments

The Journal of Cancer Metastasis and Treatment highlights that pancreatic cancer's five-year relative survival rate is as low as 11%. “The reasons for the poor prognosis of patients diagnosed with pancreatic adenocarcinoma are expected and remain the same: too few patients are diagnosed when the disease is in the early, surgically resectable stage, and too few treatment options provide durable responses,” stated researchers in the publication.

Early-stage pancreatic cancer may be treated through surgical interventions. The type of surgical intervention will depend on the stage and the location of pancreatic cancer. A pancreaticoduodenectomy — commonly referred to as a Whipple procedure — may be used to treat tumors in the pancreatic head. This procedure requires the removal of the pancreatic head, duodenum, gallbladder, parts of the bile duct, and nearby lymph nodes. The surgeon reconnects the remaining portions to allow digestion.

A distal pancreatectomy can be used to remove the pancreatic body, tail, and spleen at times.

In some cases, a total pancreatectomy may be done to remove the entire pancreas; however, patients will be required to take insulin and enzyme replacements for the rest of their lives. According to the Mayo Clinic, the final, often most complex, surgical option is for people where pancreatic cancer has advanced to nearby blood vessels. The organization states, “many people with advanced pancreatic cancer aren't considered eligible for the Whipple procedure or other pancreatic surgeries if their tumors involve nearby blood vessels. At highly specialized and experienced medical centers, surgeons may offer pancreatic surgery operations that include removing and reconstructing affected blood vessels.”

Additional forms of therapy may include chemotherapy, radiation, or a combination of the two. Providers may consider palliative care for patients whose cancer has advanced beyond the point of treatment.

Ongoing Research

There have been many advancements in pancreatic cancer care throughout the past few decades. Although these advancements, such as the approval of new chemotherapy drugs, have been beneficial, ongoing clinical trials and research aim to improve diagnostic and treatment methods.

Diagnostic Research

Despite the progression and newly available tools, there are still no definitive ways to detect pancreatic cancer before disease progression. However, many researchers are working toward the development of diagnostic tools.

As previously mentioned, newly onset diabetes may be a symptom of pancreatic cancer. According to the National Cancer Institute (NCI), 1% of all people with newly onset diabetes are diagnosed with pancreatic cancer within three years of their diabetes diagnosis. Additionally, 25% of pancreatic cancer patients have a diabetes diagnosis. With an understanding of the link between newly diagnosed diabetes and pancreatic cancer, the NCI has funded the New Onset Diabetes Study. This study will continue, until 2025, to enroll people with new-onset diabetes or hyperglycemia to develop a blood test that can help detect the risk of pancreatic cancers.

Additional research done through the Pancreatic Cancer Detection consortium is trying to develop a blood test to help detect pancreatic cancer in the general population.

Early-Stage Treatment Research

For early-stage pancreatic cancer, current clinical trials are looking at new adjuvant chemotherapy drug combinations and comparing them to standard treatments. Neoadjuvant chemotherapy is also being explored. This chemotherapy is delivered before surgery to shrink the tumor and ease resection.

Advanced Stage Treatment Research

RAS-directed therapies focus on RAS, a tumor-suppressing gene that can cause uncontrolled cell proliferation when mutated. Mutations in this gene are observed in over 90% of pancreatic cancer cases. According to the NCI, ongoing clinical trials aim to treat mutant RAS. The NCI states, “researchers have found that drugs blocking the activity of proteins that mediate the effects of RAS force cancer cells to rely on a way of creating energy called autophagy. A study in mice found that a combination of two drugs shrank pancreatic tumors. One drug targets a protein that RAS works through, and the other drug blocks autophagy. Whether such combinations will be effective in pancreatic patients is still being studied.”

Another research area is focused on immunotherapy. Pembrolizumab, otherwise known as Keytruda, is being explored for pancreatic cancer treatment. A small portion of pancreatic cancer patients has high microsatellite instability (MCI) due to tumor mutations. Keytruda has been approved for cancer patients with high MCI and acts as an immune checkpoint inhibitor to help the patient’s immune system fight the tumor.

Other researchers are exploring immune checkpoint inhibitor combinations for patients where a single immunotherapy treatment is insufficient. “For example, combining immune checkpoint inhibitors with a type of drug called CD40 agonist (which helps activate T cells) has shown some evidence of benefit in patients with advanced pancreatic cancer,” states the NCI.

Additional research on combinatory drugs, treatments, and natural killer cells is being conducted to treat advanced-stage pancreatic cancer.

Finally, stroma-modifying drugs to address the dense stroma in most pancreatic tumors are being explored. Many experts believe that these drugs can make it easier for chemotherapy to reach cancer cells.

As pancreatic cancer incidence and mortality rates continue to rise, clinicians hope that new treatment and diagnostic tools will become available.