Pancreatic cancer is considered stage IV if it has spread to distant locations in the body, such as the liver, lungs, or adjacent organs including the stomach, spleen, and/or the bowel. Sometimes it can only be determined that a pancreatic cancer is in stage IV once surgery is completed.1
Stage IV Pancreatic Cancer is Broadly Divided into Two Groups:
- Stage IVA pancreatic cancer is locally confined, but involves adjacent organs or blood vessels, thereby hindering surgical removal. Stage IVA pancreatic cancer is also referred to as localized or locally advanced.
- Stage IVB pancreatic cancer has spread to distant organs, most commonly the liver. Stage IVB pancreatic cancer is also called metastatic. The goal of treatment for patients with localized IVA disease is to induce a remission, or a disease-free period that may last months or years. Management of patients with Stage IVB disease is often aimed at controlling symptoms and pain from the cancer.
Treatment of Localized Stage IVA Pancreatic Cancer
Pancreatic cancer is often not diagnosed until it is in Stage IVA, meaning the cancer has invaded adjacent organs or major blood vessels. When this occurs surgical removal of the cancer (which provides a chance at long-term cure) is seldom an option. Therefore, the goal of treatment of patients with Stage IVA pancreatic cancer is to induce a remission, which is a cancer-free period that may last months or years, and to prevent and control symptoms.
Treatment for Stage IVA pancreatic cancer may include palliative surgery, and systemic chemotherapy, or chemoradiation, which is chemotherapy and radiation delivered together. Occasionally, a surgical bypass procedure may be performed to alleviate complications of the cancer, such as jaundice, intestinal obstruction, or pain, thereby improving quality of life.1,2
Treatment of Non-localized Stage IVB (Metastatic) Pancreatic Cancer
The majority of patients with Stage IV cancer have metastatic disease (Stage IVB), which means that cancer has spread to distant locations in the body that often include the liver and other areas of the abdominal cavity. To kill cancer cells that have spread throughout the body, a systemic treatment is necessary, and this is typically chemotherapy.
Systemic Therapy: Precision Cancer Medicines, Chemotherapy, and Immunotherapy
Systemic therapy is treatment directed at destroying cancer cells throughout the body. Because patients with pancreatic cancer have small amounts of cancer that have spread away from the pancreas, an effective systemic treatment is needed to cleanse the body of these cells in order to prolong survival and improve the chance of cure. Systemic therapy may include chemotherapy, precision cancer medicines, immunotherapy or a combination of these therapies.3,4,5,6,7,8
The results of a phase III trial presented at the 2019 annual meeting of the American Society of Clinical Oncology (ASCO) show that the Lynparza PARP inhibitor delays cancer progression and improves survival when used to treat BRCA-mutated pancreatic cancer and is the first precision cancer medicine to become available for the treatment of pancreatic cancer.
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA. When either of these genes is mutated, or altered DNA damage may not be repaired properly, and the cells are more likely to develop additional genetic alterations that can lead to cancer. All patients should undergo genomic biomarker testing for these and other markers.8
Chemotherapy is any treatment involving the use of drugs to kill cancer cells and may consist of single drugs or combinations of drugs and can be administered through a vein or delivered orally in the form of a pill. Chemotherapy is commonly used to treat both locally advanced (Stage IVA) and metastatic (Stage IVB) pancreatic cancer.
Gemzar® (gemcitabine): The standard treatment of stage IV pancreatic cancer is systemic therapy with Gemzar® based chemotherapy or participation in a clinical trial evaluating new chemotherapy or precision cancer medicines.5
Combining chemotherapy with radiation therapy, a technique called chemoradiation, may provide more benefit than chemotherapy alone for some patients with Stage IVA pancreatic cancer but is not typically a treatment for patients with Stage IVB disease.2,3
Strategies to Improve Treatment
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Areas of active investigation aimed at improving the treatment of pancreatic cancer include the following:
Precision Cancer Medicines
Research is ongoing to develop new medications that specifically target cancer cells in clinical trials. These trials require a sample of the cancer or liquid biopsy to be available in order to evaluate for biomarkers. Patients should learn about options to participate in these trials prior to surgery in order to ensure that cancer tissue is obtained correctly.3,4,5,6,7,8
Phase I Clinical Trials
New chemotherapy drugs continue to be developed and evaluated in patients with advanced cancers in Phase I clinical trials. The purpose of Phase I trials is to evaluate new drugs in order to determine the safety and tolerability of a drug and the best way of administering the drug to patients.
1 Pancreatic Cancer Action. Facts and statistics. Accessed February 2019 from pancreaticcanceraction.org/about-pancreatic-cancer/medical-professionals/stats-facts/facts-and-statistics
2 Hazard L, Tward JD, Szabo A, Shrieve DC. Radiation therapy is associated with improved survival in patients with pancreatic adenocarcinoma: results of a study from the Surveillance, Epidemiology, and End Results (SEER) registry data. Cancer. 2007; 110:2191-201.
5 Safran H, Ramanathan R, Schwartz J, King T, et al. Herceptin and Gemcitabine for Metastatic Pancreatic Cancers That Overexpress her-2/neu. Proceedings from the 37th Annual Meeting of the American Society of Clinical Oncology 2001, San Francisco CA, Abstract #517.
6 Cascinu S, Berardi R, Labianca R, et al. Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in patients with advanced pancreatic cancer: a randomised, multicentre, Phase II trial. Lancet Oncology. 2008;9:39-44.
7 Toubaji A, Achtar M, Provenzano M et al. Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers.Cancer Immunol Immunother. 2008 Feb 23.