Two prospective studies that followed individuals with genetic or familiar risk for pancreatic cancer found that patients whose cancer was found through screening had better overall survival than those diagnosed symptomatically, suggesting that surveillance in this population may improve outcomes.
Opponents of screening for pancreatic cancer in this population suggested that screening may identify cancers at an earlier stage but doesn’t necessarily improve outcomes – an effect referred to as lead-time bias. “The data from these studies strongly refute this, now showing substantially better outcomes for those with screen-detected pancreatic cancer. In other words, these data now strongly suggest that, for some cases, earlier detection truly leads to superior outcomes, including what appears to be substantially higher likelihood of long-term cure,” said Matthew B. Yurgelun, MD, who wrote an accompanying editorial that was published in the Journal of Clinical Oncology, in response to two studies published in June in the journal.
“Individuals with genetic or familial risk of pancreatic cancer who develop screen-detected pancreatic cancer, as opposed to pancreatic cancer detected due to symptoms and in the absence of screening, appear to have significantly better outcomes compared to historical pancreatic cancer outcomes data,” said Dr. Yurgelun, who is an assistant professor of medicine at Harvard Medical School and director of the Dana-Farber Cancer Institute Lynch Syndrome Center, Boston.
In one report, researchers reported outcomes from 1,461 genetic high-risk participants in Cancer of Pancreas Screening-5 (CAPS5). 48.5% had a pathogenic version of a PDAC-susceptibility gene. 10 individuals were diagnosed with PDAC, 9 during surveillance, and 1 after having dropped out of the surveillance program for 4 years. 7 of the 9 surveillance cancers were stage 1, 1 was stage 2, and 1 was stage 3. 8 of 9 were resectable. The cancer found outside of surveillance was metastatic. In the overall cohort of 1,731 individuals, there were 19 PDACs detected during surveillance and 7 diagnosed outside of surveillance. 57.9% of surveillance-discovered were stage 1 and 5.2% were stage 4. On the other hand, 6 of the 7 tumors found outside of surveillance were stage 4. Median survival was 9.8 years in the screen-detected group versus 1.5 years outside surveillance (hazard ratio, 0.13; P = .003).
In a second study, researchers followed 47 individuals with inherited pathogenic variants for a median of 56 years. 8.9% were diagnosed with PDAC over a median follow-up of 5.6 years. By age 70, 20.7% had been diagnosed with PDAC. 83.3% of cases were identified as resectable at imaging, and 71.0% underwent resection. 33.3% of cases were stage I. Following primary PDAC diagnosis, the median survival was 26.8 months. 5-year survival was 32.4% (95% confidence interval; 19.1-54.8%). Among those who underwent rsection, the 5-year survival was 44.1% (95% CI, 27.2-71.3%). 2.6% of the population underwent surgery to remove a suspected malignant lesion which turned out not to be PDAC. 5 had low-grade dysplasia.
The results reinforce existing clinical practice guidelines that suggest MRI or endoscopic ultrasound screening for individuals with both a family and genetic risk of PDAC and could inform deliberations about extending such screening to all patients with inherited risk factors, according to Dr. Yurgelun.
Screening does not come without drawbacks. Research has demonstrated that about 40% of individuals who present for high-risk screening have pancreatic abnormalities, typically cystic lesions. These are also common in the general population. Very few such lesions require intervention, but they should be monitored, according to Dr. Yurgelun. Biopsies can be tricky, and removal requires major abdominal surgery, and magnetic resonance imaging or endoscopic ultrasonic can be nuanced, “which highlights the importance of this screening being performed and interpreted by health care providers experienced in high-risk surveillance,” Dr. Yurgelun said.
Dr. Yurgelun has no relevant financial disclosures.