Study: Screening for pancreatic cancer detects early-stage disease and improves survival

IN-DEPTH REVIEW OF RESEARCH
 

Study background

Some individuals have an increased risk for pancreatic cancer because of an inherited mutation or a family history of the disease. Pancreatic cancer is rare in the general population, and people are considered to be at high risk if they have a five percent or higher lifetime risk. Currently, no effective screening methods exist for detecting early-stage pancreatic cancer. As a result, pancreatic cancer is one of the deadliest cancers worldwide.

Johns Hopkins University began its Cancer of the Pancreas Screening (CAPS) studies in 1998 to determine “the effectiveness of early detection screening in high-risk individuals of pancreatic cancer" and to discover "new biomarkers to improve early detection.” Over the past two decades, the CAPS study and others have shown that screening for pancreatic cancer in high-risk individuals without symptoms has the potential to detect the disease in its early stages and improve survival outcomes. The most recent CAPS study (CAPS5) confirms and strengthens these findings.

Researchers of this study wanted to know

The researchers of this study wanted to evaluate the outcomes (cancer diagnosis and survival) among high-risk patients undergoing surveillance for pancreatic cancer.

Populations looked at in this study

Participants in the CAPS-5 study were known to have either an inherited mutation that increased their risk for pancreatic cancer (44 percent: 643 of 1,461 participants) or a strong family history of the disease but no know mutation (56 percent: 818 of 1,461 participants).

• Among participants with inherited mutations:
  • 18.4% (269) had a BRCA2 mutation and at least one first- or second-degree relative with a history of pancreatic cancer.
  • 4.7% (68) had a BRCA1 mutation with at least one first-degree relative with a history of pancreatic cancer.
  • 4.7% (69) had a CDKN2A mutation, which is associated with Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM). People with FAMMM have an increased lifetime risk of developing melanoma and pancreatic cancer.
  • 4.0% (58) had Lynch syndrome with at least one first- or second-degree relative with a history of pancreatic cancer.
  • 4.2% (62) had a PALB2 mutation with at least one first- or second-degree relative with a history of pancreatic cancer.
  • 6.4% (93) had an ATM mutation with at least one first- or second-degree relative with a history of pancreatic cancer.
  • 1.2% (18) had an STK11 mutation, which is associated with Peutz-Jeghers syndrome.
  • 0.4% (6) had more than one inherited mutation and at least one first- or second-degree relative with a history of pancreatic cancer.
• Among participants who did not have a known inherited mutation but had a family history of pancreatic cancer:
  • 23.7% (346) had at least two or more first-degree relatives with a history of pancreatic cancer.
  • 27.5% (402) had one first-degree relative and one or more second-degree relatives with a history of pancreatic cancer.
  • 0.3% (5) had one first-degree relative with young-onset pancreatic cancer (50 years old or younger).
  • 4.5% (65) met other criteria which allowed them to be included in the high-risk group.
• Participant demographics:
  • The average age of participants was 60.3 years.
  • 31.1% had a personal history of cancer (mostly breast cancer).
  • 32% were never/former smokers.
• 3.9% were current smokers.
  • 51.8% used alcohol.
  • 9.8% had a history of diabetes (type 1 or 2).
  • 64.6% were female.
  • 94.5% were white.
  • 3.5% were Black.
  • 1.3% were Asian.
  • 2.4% were Hispanic/Latino.
  • 0.7% identified as other/multiple.

Study design

The CAPS-5 study is a prospective study with participants from eight medical centers in the United States. Enrollment opened in 2014 for individuals that met the high-risk and age criteria. The authors of this study report on all participants enrolled through June 2021.

Screening consisted of yearly imaging of the pancreas with either an endoscopic ultrasound (EUS) or magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP). Each year, participants also donated a blood sample that was used for research purposes.  If the medical team found significant lesions, participants had more frequent surveillance (every 3 to 6 months) to monitor changes. If the team suspected cancer or precancer, participants had surgery and treatment based on current recommendations.

The study also included a group of people with pancreatic disease and a group of healthy people to compare to participants in the high-risk group. Patients with pancreatic disease had pancreatic cancer, pancreatic cysts or chronic pancreatitis (inflammation of the pancreas). Healthy people were patients with a normal pancreas who were undergoing routine upper GI endoscopy (EGD), screening colonoscopy or endoscopic retrograde cholangiopancreatography (ERCP) as part of their standard medical care.

Study findings

CAPS-5 study

Nine participants were diagnosed with pancreatic cancer detected by screening during the study:

• 7 had stage I cancer:
  • 4 of the 7 had a family history of pancreatic cancer with no known inherited mutation.
  • 2 of the 7 had inherited mutations and a family history of pancreatic cancer (BRCA2, PALB2).
  • 1 of the 7 had inherited mutations with no family history of pancreatic cancer (CDKN2A).
• 1 had stage IIB cancer:
  • This person had a family history of pancreatic cancer with no known inherited mutation.
• 1 had stage III cancer:
  • This person had an inherited mutation and a family history of pancreatic cancer (BRCA1).
• 8 had surgically resectable cancer.
• 7 of the 9 participants who were diagnosed with pancreatic cancer are still alive with a median survival of 3.84 years at the time this study was written.

Eight participants had surgery for concerning cystic lesions on the pancreas:

• 3 had high-grade dysplasia (precancer that is likely to become cancerous).
• 5 had low-grade dysplasia (precancer that is unlikely to become cancerous).

One participant discontinued surveillance, then developed symptoms and was diagnosed with stage IV pancreatic cancer four years later.

Combined CAPS1-5 studies

Twenty-six participants have been diagnosed with pancreatic cancer since the program began in 1998.

• 38.5% had a known inherited mutation.
• 19 had cancers that were detected by screening, of which:
  • 57.9% were stage I.
  • 15.8% stage II.
  • 21.1% stage III.
  • 5.2% stage IV.
• 7 had cancers that were detected outside of surveillance, of which 85.7% were stage IV.
• Participants with screening-detected pancreatic cancer had an overall 5-year survival of 73.3% (compared to 5 to 10% in participants with cancer detected outside of surveillance).

Strengths and limitations

Strengths

• This is a phase 3 clinical trial.  It is a multicenter, interdisciplinary study that has been ongoing for more than 20 years.
• The study includes individuals with a mix of different mutations and family histories associated with an increased risk of pancreatic cancer.

Limitations

• The follow-up period for the CAPS-5 cohort was short ( median 4 years) so it is difficult to draw conclusions about long-term survival for this group. Longer follow-up time is needed to fully understand the benefits of endoscopic ultrasound and MRI-based surveillance in high-risk individuals and to evaluate the usefulness of blood biomarker tests in early disease detection.
• A relatively small number of pancreatic cancers (26) have been diagnosed during the entire CAPS program. This small sample size limits the reliability of the results. As more people are diagnosed with pancreatic cancer by screening and followed up long-term, patterns in stage at diagnosis and survival rates will become clearer.
• The participants were mostly white (94.5%) so the results might not be generalizable across diverse populations.
   

Context

In recent years, screening for pancreatic cancer has shown promise in detecting the disease early, when it is most treatable. However, that conclusion is based on a small number of studies and a small number of pancreatic cancer cases because pancreatic cancer is relatively rare even in high-risk populations. Additionally, most of these studies do not yet have long-term follow-up results, making it hard to predict how screening affects long-term survival.

Current evidence from the CAPS studies and others suggests that screening can be beneficial for high-risk individuals, and the results of the most recent study will likely change screening guidelines for this population. The American Society for Gastrointestinal Endoscopy (ASGE) released a new guideline in early 2022 that recommends pancreatic cancer screening for people with an increased risk for developing the disease. ASGE based their guideline on studies in this field that showed screening for pancreatic cancer in high-risk groups was associated with earlier diagnosis, better survival outcomes and few adverse events.
 

Conclusions

This study confirms that screening for pancreatic cancer in asymptomatic, high-risk individuals can lead to earlier detection of the disease and better survival outcomes. The results may change national screening guidelines for high-risk populations from “consider screening” to “recommend screening.”

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posted 8/30/22

This review was updated on 09/15/2022 to correct typo describing changes in eligibility.