Pancreatic Carcinoma Metastatic

Metastatic pancreatic cancer, also called stage IV pancreatic cancer, is a highly aggressive disease where cancer cells have spread beyond the pancreas to distant organs. Despite a grim outlook, with a five-year survival rate as low as 2%, recent advances in treatment are offering new hope to patients facing this challenging diagnosis.

Table of contents

• What Is Metastatic Pancreatic Cancer?
• Signs and Symptoms
• How Is It Detected?
• Where Does the Cancer Spread?
• Survival and Prognosis
• Treatment Options
• Living with Metastatic Pancreatic Cancer

What Is Metastatic Pancreatic Cancer?

Metastatic pancreatic cancer occurs when cancer cells that started in the pancreas have spread to other parts of the body^[3]. The pancreas is a gland located behind the stomach that helps break down food and controls blood sugar levels through hormone production^[2]. When cancer develops in the pancreas and spreads to distant organs, it is classified as stage IV or advanced pancreatic cancer.

Though the cancer has spread to other areas of the body, it is still called pancreatic cancer because that is where it started^[3]. Pancreatic cancer is particularly aggressive, and most patients are diagnosed at an advanced stage because early symptoms are often vague or absent^[1].

Metastatic pancreatic cancer is considered unresectable, meaning it cannot be removed through surgery^[3]. The cancer has either spread to nearby blood vessels and lymph nodes or to distant organs. However, it’s important to understand that a diagnosis of metastatic pancreatic cancer does not necessarily mean death is immediate. Instead, treatment focuses on managing symptoms, improving quality of life, and potentially slowing cancer growth^[3].

The most common type of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of pancreatic cancer cases^[6]. This is a highly aggressive and lethal form of the disease.

Signs and Symptoms

Early on, pancreatic cancer may not cause any signs or symptoms, making it extremely difficult to detect^[2]. Most people don’t experience symptoms until the disease has progressed to an advanced stage^[6].

As metastatic pancreatic cancer grows, people may notice the following symptoms^[2][6]:

• Jaundice (yellowing of the skin and whites of the eyes)
• Light-colored stools
• Dark-colored urine
• Pain in the upper or middle abdomen and back
• Unexplained weight loss
• Loss of appetite
• Nausea and vomiting
• Fatigue (extreme tiredness)
• Itchy skin
• Gas or bloating
• Blood clots
• New-onset diabetes or worsening diabetes

A person with advanced pancreatic cancer may also experience ascites, which is a buildup of fluid in the abdomen^[3]. Symptoms such as jaundice or unexplained weight loss should prompt immediate medical attention and discussion about pancreatic cancer^[3].

How Is It Detected?

Pancreatic cancer is difficult to diagnose early because the pancreas is located deep within the body, surrounded by other organs such as the small intestine, liver, and spleen^[6]. Early changes are often without symptoms and hard to detect.

Imaging studies are the only way to see a pancreatic tumor^[3]. Doctors typically use several types of tests to diagnose and determine if pancreatic cancer has spread:

• Computed tomography (CT) scan: This is most commonly used to see if cancer has spread to nearby organs^[3].
• Magnetic resonance imaging (MRI): This may be used along with CT scans to provide additional detailed images.
• Positron emission tomography (PET) scan: PET scans can help determine if treatment is working effectively and if cancer has spread to distant locations^[17].
• Endoscopic retrograde cholangiopancreatography (ERCP): This is less commonly used but can help visualize the pancreatic ducts.

Doctors may also perform genetic testing and blood tests to better understand the cancer’s behavior and identify potential treatment options^[17]. Novel genetic testing can analyze blood samples to detect cancer DNA, helping experts determine who might be at risk for cancer recurrence^[17].

Where Does the Cancer Spread?

Pancreatic cancer most commonly spreads to the liver^[5]. Other common sites where pancreatic cancer can spread include^[5]:

• Abdominal wall
• Lungs
• Bones
• Distant lymph nodes

When cancer spreads to another area of the body, it is called metastatic cancer. Even though the cancer has moved to other organs, it is still called pancreatic cancer because that is where it originated^[3].

Survival and Prognosis

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide and is predicted to become the second leading cause of cancer-related death in Western countries in the coming decades^[1]. It has the lowest five-year survival rate of all cancers, at only 9% for all stages combined^[1].

For metastatic pancreatic cancer specifically, the five-year overall survival rate is even poorer, as low as 2%, with a median survival expectancy of less than one year with current treatments^[1][6]. However, these statistics represent averages and do not predict what will happen to any individual patient.

Recent advances in treatment are helping people with pancreatic cancer live longer^[17]. New treatment methods, including improved chemotherapy combinations and targeted therapies, are leading to improved survival and quality of life for some patients.

Treatment Options

The goal of treatment for metastatic pancreatic cancer is to control symptoms, improve quality of life, and potentially shrink the cancer or slow its growth^[3]. Treatment options may include chemotherapy, targeted therapy, immunotherapy, and palliative care.

Chemotherapy

Chemotherapy is the standard treatment for metastatic pancreatic cancer^[9]. Over recent years, treatment has evolved from single-agent therapy to combination chemotherapy regimens.

Current first-line chemotherapy options for patients with good performance status include^[9]:

• FOLFIRINOX: A combination of four drugs (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin)
• Gemcitabine plus nab-paclitaxel (Abraxane): A combination therapy that has shown promising results

For patients with poorer performance status, single-agent gemcitabine remains a valid treatment option^[9].

In February 2024, the FDA approved a new first-line treatment called NALIRIFOX for patients with metastatic pancreatic cancer who have not received previous treatment^[11]. NALIRIFOX is a combination of liposomal irinotecan, 5-fluorouracil/leucovorin, and oxaliplatin. This represents the first approval for a first-line treatment for metastatic pancreatic cancer in over ten years.

For second-line treatment, after first-line therapy has failed, the combination of 5-FU/FA plus nanoliposomal irinotecan has shown superior overall survival compared to 5-FU/FA alone^[9].

Targeted Therapy

Targeted therapies are treatments directed at blocking certain genes or proteins specific to cancer cells^[6]. Some patients may benefit from targeted therapies based on the genetic makeup of their cancer.

For patients with a BRCA1 or BRCA2 germline mutation (present in about 5% of pancreatic cancer patients), the PARP inhibitor olaparib has been shown to improve progression-free survival when used as maintenance treatment after at least 16 weeks of platinum-based chemotherapy^[9]. Patients with metastatic pancreatic cancer should be tested early for BRCA mutations to identify if they might benefit from this treatment.

Immunotherapy

Immunotherapy uses the body’s own immune system to fight cancer. Currently, two FDA-approved immunotherapy options are available for small subsets of patients with pancreatic cancer^[12]:

• Dostarlimab (Jemperli): Approved for patients with advanced pancreatic cancer that has DNA mismatch repair deficiency (dMMR)
• Pembrolizumab (Keytruda): Approved for patients with advanced pancreatic cancer that has high microsatellite instability (MSI-H), DNA mismatch repair deficiency (dMMR), or high tumor mutational burden (TMB-H)

These immunotherapies target the PD-1/PD-L1 pathway. However, only about 1% of pancreatic cancers have high microsatellite instability, and only a portion of these patients benefit substantially from checkpoint inhibitor treatment^[12].

Palliative Care and Symptom Management

Palliative care provides treatment to manage symptoms and give the best possible quality of life^[22]. It acknowledges that death is a part of life and a natural process, but does not aim to speed up or slow down death. Instead, it supports patients and their loved ones throughout the disease.

Palliative treatments for metastatic pancreatic cancer may include^[3][18]:

• Stent placement: A tube placed in the bile duct or bowel to relieve blockages
• Pain management: Medications to control pain
• Medications for nausea and vomiting: Drugs like somatostatin or octreotide to reduce digestive fluid buildup
• Nutritional support: Help with eating and maintaining weight
• Blood transfusions: To address anemia and increase energy levels^[18]

Palliative care can be provided alongside other treatments and does not mean giving up hope^[22].

Clinical Trials

Due to the limited effective treatment options for pancreatic cancer, patients are highly encouraged to consider clinical trials at all stages^[12]. Clinical trials test new treatments and approaches that may offer additional hope. Research is ongoing into new therapeutic targets, including gene fusions, DNA damage repair deficiency, and personalized treatments based on tumor characteristics^[9].

Living with Metastatic Pancreatic Cancer

A diagnosis of metastatic pancreatic cancer can be frightening and overwhelming. However, it’s important to remember that advanced cancer does not mean there is no hope or no treatment available^[3].

Managing Symptoms

Tell your doctor or nurse about any symptoms you experience so they can help manage them^[18]. Common symptoms that can be managed include:

• Fatigue: Rest regularly throughout the day, but also try gentle exercise like short walks, which research shows can increase energy^[18].
• Pain: Work with your healthcare team to find effective pain relief medications.
• Digestive problems: Medications can help with nausea, vomiting, and bowel blockages.
• Loss of appetite: A dietitian can provide advice on nutrition and managing weight loss^[18].

Emotional and Practical Support

Living with metastatic pancreatic cancer affects not just the body but also emotions, relationships, and practical matters. Support is available from many sources:

• Healthcare teams, including doctors, nurses, and social workers
• Palliative care specialists who focus on quality of life
• Support groups where you can connect with others facing similar challenges
• Counselors or therapists who can help with emotional challenges
• Patient advocacy organizations that provide resources and information

For caregivers, it’s important to practice self-care, ask for help when needed, and seek support from friends, family, or caregiver support groups^[16].

Hope and Progress

While pancreatic cancer remains a challenging disease, progress is being made. People with pancreatic cancer are living longer thanks to improved treatment approaches^[17]. New therapies are being developed and tested, and researchers continue to work toward better understanding the disease and finding more effective treatments.

Some patients have lived for years with metastatic pancreatic cancer, far exceeding initial prognoses^[20]. Each person’s experience is unique, and it’s important not to give up hope.