The U.S. Preventive Services Task Force (USPSTF) recently released the reaffirmation of its recommendation against screening for pancreatic cancer in asymptomatic adults. Despite its poor prognosis, the USPSTF cites potential harms of screening, false-positives, and unnecessary treatment, as well as a lack of biomarkers for the disease, specified screening, and a low incidence rate for evidence against screening in the average adult population.
Though it is an uncommon form of cancer, the USPSTF predicts pancreatic cancer will soon be the second-leading cause of death in the U.S., with an estimated 56,770 people diagnosed and 45,750 of those dying from the disease in 2019. Of those diagnosed with pancreatic cancer, 85-90 percent have no known familial risk of genetic syndromes, 5-10 percent have familial risk, and 3-5 percent of cases are due to inherited genetic cancer syndromes, such as Peutz-Jeghers syndrome (JAMA 2019; doi:10.1001/JAMA.2019.10232). Though the age-adjusted annual incidence of pancreatic cancer is just 12.9 cases per 100,000 person-years, the death rate is 11.0 deaths per 100,000 person years, primarily because the prognosis of the disease is so poor, according to the JAMA article.
The overall 5-year survival rate of pancreatic cancer is 9.3 percent, with survival rates varying depending on the state at which it is diagnosed, the USPSTF article noted. The 5-year survival rate for localized pancreatic cancer is 37.4 percent; when regional disease is present, the 5-year survival rate is 12.4 percent; and when distant metastatic disease is present, the 5-year survival rate is just 2.9 percent, per JAMA. Early-stage surgical intervention is the most likely treatment to improve survival chances; however, most cases of pancreatic cancer are detected at an advanced stage when surgical resection is unlikely to be beneficial to the patient, the USPSTF reported.
Recommendations
In its report, the USPSTF found no evidence that screening for pancreatic cancer or treatment of self-detected pancreatic cancer improves disease-specific morbidity or mortality, or all-cause mortality. It reported adequate evidence that the magnitudes of the benefits of screening for pancreatic cancer in asymptomatic adults is minimal and that the magnitude of the harms of screening and treatment of screen-detected pancreatic cancer is at least moderate, concluding that the potential benefits of screening for pancreatic cancer do not outweigh potential harms.
"It's important to note that this is the guideline for the general population," noted Florencia McAllister, MD, Assistant Professor in the Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, MD Anderson Cancer Center. "The incidence of pancreatic cancer is so low that it would not justify screening the general population, and medical screenings are not simple," she said. "When considering the inconvenience to the patient and the financial costs, the recommendation against screening for the general population makes sense."
McAllister noted that any patients with risk factors should be screened. "The high-risk population is where screening should start. "Any patients with a strong family history of pancreatic cancer, such as those with a first degree and second degree relative on the same side of the family, should be screened, as well as those with known or unknown mutations." McAllister noted that those two risk factors are not always both present, and that patients with mutations may or may not have a family history, depending on the gene.
Screening
Adding to the USPSTF's recommendation against screening for pancreatic cancer in asymptomatic adults is the lack of testing designed specifically for the disease. Current methods of screening, such as image-based screening tests including computed tomography (CT) scan, magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS), have no evidence of accuracy for detecting pancreatic cancer. In addition, there are currently no accurate, validated biomarkers for early detection of the disease, USPSTF reported.
"When recommending an MRI for screening of pancreatic cancer, the clinician must be aware of potential long-term side effects," McAllister said. "Side effects have been reported, but it's currently unclear how many there are or how long they will last." The USPSTF found no studies that reported on the sensitivity or specificity of CT scan, MRI, or EUS as a screening tool for pancreatic cancer, but it did report adequate, indirect evidence that the magnitude of the harm of screening is at least moderate, based on potential harms from false-positive results and the harms of treatment.
Individual Cases
The USPSTF noted the importance of viewing the screening guidelines as just that-a guideline for asymptomatic adults-and in considering patients individually for other considerations. In its JAMA release, it recognized that clinical decisions involve more considerations than evidence alone, including policy and coverage decisions and evidence of clinical benefits and harms. "For the general population, patients that do not have an elevated risk are recommended against screening," McAllister reiterated. "However, it is important to view a patient's risk factors in addition to hereditary results, including obesity, history of smoking, and mutations. If there are multiple risk factors, she or he becomes a high-risk patient; but with only one risk factor and without a genetic mutation, screening is not recommended."
In addition to the risk factors mentioned by McAllister, the USPSTF included new-onset diabetes, preexisting diabetes, older age, and a history of chronic pancreatitis as risks for developing pancreatic cancer. "Early-onset diabetes is a red flag for early pancreatic cancer," McAllister said. "In general, encouraging patients to lead a healthier lifestyle, such as eating less processed food and meat and increasing the amount of fiber, fruits, and vegetables in the diet, could help reduce the risk. Exercising and avoiding high sugar consumption is also recommended, but in the big picture, it's just about having a healthy lifestyle."
Looking Forward
As research around pancreatic cancer moves forward, the USPSTF identified several areas for needed development, including identifying effective screening tests with high sensitivity and high specificity for pancreatic cancer and high-grade precursor lesions. Additional research is also needed to better understand the prevalence and natural history of precursor lesions to pancreatic cancer, including the likelihood of progression, USPSTF noted. Further research investigating the benefits and harms of screening for pancreatic cancer in patients with a high risk due to history of familial pancreatic cancer and inherited genetic syndromes is needed, according to the JAMA article.
The USPSTF also noted that pancreatectomy carries a significant risk of morbidity and mortality, and the prognosis for more advanced pancreatic cancer, which is not amenable to surgery is poor, requiring research on better treatments for all stages of the disease to improve long-term survival and limit the harms of treatment. "There are several multi-institutional groups studying the high-risk population," McAllister stated. "Our strongest results will come from those studies, which may give hope for identification of a biomarker, better methodology and forms of screening, and noninvasive treatment of pancreatic cancer."
Kelly Wolfgang is a contributing writer.
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