‘Persuasive’ data show screening high-risk individuals improves pancreatic cancer outcomes
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Key takeaways:
- Surveillance led to detection of smaller tumors among patients at high risk for pancreatic cancer.
- Individuals who underwent screening lived significantly longer than those who did not.
Surveillance of individuals at a high risk for pancreatic ductal adenocarcinoma led to the detection of smaller, earlier-stage tumors, according to results of a comparative cohort study.
The surveillance approach also resulted in considerably longer median survival.
“For those who potentially were dubious about such magnitude of benefit, the results are persuasive,” study co-author Marcia Irene Canto, MD, MHS, professor of medicine and oncology at Johns Hopkins University, told Healio.
Background
Pancreatic ductal adenocarcinoma (PDAC) is the third most common cause of cancer death in the U.S.
Only 11% of individuals live 5 years after diagnosis, largely due to detection at late stages when the cancer has metastasized and is no longer resectable.
Although population-based screening is not recommended, prior research suggested selective surveillance could provide benefit.
The Cancer of the Pancreas Screening (CAPS) program — which screens high-risk individuals with family history or genetic predisposition to pancreatic cancer —
showed surgical downstaging of cancers and, eventually, a significant survival benefit, she said.
However, many did not see value in pancreatic cancer surveillance.
“People were still not convinced,” Canto said. “There was some question about bias — particularly lead-time bias, when you detect a disease much earlier in relatively healthy asymptomatic individuals but then the outcome is the same. People still die, and it’s the same as if you did not do any screening or surveillance. There is also some concern about costs and implementation in the general population.”
Canto and colleagues conducted their comparative cohort study to further investigate the impact of surveillance among high-risk individuals on stage of diagnosis and survival.
Methodology
Researchers used CAPS — which began in 1998 and continues today across multiple centers — to build a cohort of 26 high-risk individuals (mean age at diagnosis, 65.8 years; 57.7 women; 100% white) with surveillance-detected PDAC.
They defined high-risk as individuals as those who had at least two family members — including one first-degree relative — with PDAC (61.5%), or those who carried one of several genes associated with pancreatic cancer (38.5%).
Investigators used the SEER 18 database to establish a control cohort of 1,504 people with PDAC matched for sex, age and diagnosis year.
Results
Researchers reported significantly smaller median tumor diameter (2.5 cm vs. 3.6 cm; P < .001) and earlier disease stage at diagnosis (stage I, 38.5% vs. 10.3%; stage II, 30.8% vs. 25.1%; P < .001) in the surveillance-detected group.
PDAC mortality at 5 years was significantly lower in the surveillance group than the control group (43% vs. 86%; HR = 3.58; 95% CI, 2.01-6.39).
Overall, individuals in the surveillance cohort achieved significantly longer median survival (61.7 months vs. 8 months) and were five times as likely to survive at least 5 years (50% vs. 9%).
Researchers also analyzed outcomes among the 20 high-risk individuals in the surveillance group who had screen-detected PDAC. Those individuals achieved a 16-fold increase in median OS compared with matched controls (144 months vs. 9 months). They also had a higher likelihood of surviving 1 year (95% vs. 41%) and 5 years (61% vs. 9%).
“[The results were] not unexpected,” Canto said. “I take care of [these] patients. ... I know that they’re living long past the 2-year average survival that patients have when they come with clinical symptoms. We’re convinced of the benefit. It’s just a matter of convincing other people it’s of that magnitude using robust scientific methodology.”
Researchers acknowledged study limitations, including the work being conducted only at academic centers, a lack of racial/ethnic diversity, the limited number of high-risk individuals in the surveillance cohort who progressed to PDAC and the lack of a control group that consisted of high-risk individuals who did not undergo screening.
‘An opportunity for doing better’
Screening currently requires endoscopic ultrasounds and MRIs over many years. This can be a burden and costly, depending on insurance coverage, Canto said.
Additionally, such surveillance often occurs at academic centers, which are not always accessible to large portions of the population.
“The average person potentially may have to travel [a considerable distance] to get to a specialty center, and we don’t know if the outcomes will be the same in a nonspecialty center,” Canto said.
However, the study results show the effectiveness of screening for select people who progress to PDAC, Canto said.
Research continues into improving biomarkers in the blood to help with early detection. Artificial intelligence also could be a useful tool.
“It’s well known in cancer detection that with the most expert readers of imaging studies, we still miss. We’re not perfect,” Canto said. “Expert centers are now doing research in AI to help analyze thousands of pieces of data. It could fine-tune the surveillance strategy [or] even pick a subset of low-risk individuals who could get less intense surveillance or much higher-risk patients who need surgery even before cancer becomes clinically evident. AI provides such an opportunity for doing better.”
For more information:
Marcia Irene Canto, MD, MHS, can be reached at mcanto1@jhmi.edu.
Perspective
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Suneel Kamath, MD
This study is a big positive. Pancreatic cancer is such a deadly disease, so anything we can do to detect it earlier is going to translate into positive outcomes.
The difference in median OS jumps off the page. You don’t see differences like that in most studies. It is a massive difference in mortality rate, and it was a bigger magnitude of improvement than I would’ve expected.
The greatest difficulty we have to overcome with this type of data is that it relied on people who have a certain number of family members with pancreatic cancer history. A lot of people who may be suspected to have pancreatic cancer will come to their first visit and say, “I don’t really have any family history. No one has cancer in my family. This just came out of nowhere.” After a diagnosis is confirmed, they notify their family members. By their fourth or fifth visit, the patient will say, “Actually, I found out that my grandmother did have this” or “My uncle had this."
One of the main takeaways from this study is that people should talk to their relatives about their family histories. We need to prompt patients to do this, and to be detailed about different tumor types and conditions.
In most cases, a family history of cancer will be what prompts a physician to order genetic testing for cancer. If someone doesn’t know their family history, they’re not going to get tested.
Widespread screening for pancreatic cancer is not going to be possible for the general population. While the incidence is rising every year, there are still only 66,000 cases per year. Pancreatic cancer is not common enough to justify doing hereditary genetic testing for everyone. That’s why family history is so important, because it would be the gateway where we can test people for hereditary syndromes.
The main approaches we have to screen for pancreatic cancer are imaging like MRIs, CT scans or endoscopic ultrasounds. An endoscopic ultrasound is an expensive, invasive procedure and it involves anesthesia, so it carries some risks. MRI is noninvasive, but it is still expensive.
Having a noninvasive screening tool like a circulating tumor DNA test would be a big step forward. Although they’re still very expensive, a blood draw is much more logistically feasible than getting an MRI or doing an endoscopic ultrasound. To me, that is the next important area to explore.
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