‘Be very suspicious’: Staging of early pancreatic cancer inaccurate up to 80% of the time
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Key takeaways:
- More than three-quarters of patients clinically diagnosed with stage I pancreatic ductal adenocarcinoma were upstaged after surgery.
- Preoperative imaging used for staging may underestimate lymph node involvement.
Nearly 80% of individuals clinically diagnosed with stage I pancreatic ductal adenocarcinoma and close to 30% diagnosed with stage II disease got upstaged after surgery, according to retrospective study results.
The findings suggest preoperative imaging used for clinical staging may not adequately detect lymph node involvement in up to four of every five patients analyzed, researchers concluded.
“When you see [a patient with] stage I disease, as clinicians, we should be very suspicious about the accuracy of staging,” Srinivas Gaddam, MD, MPH, associate director of pancreatic biliary research and associate professor at Cedars-Sinai Medical Center, told Healio.
Background
Early detection of pancreatic ductal adenocarcinoma is critical, as 5-year survival rates are dramatically higher for people diagnosed with stage IA disease (83.7%) than stage IV disease (3%), according to study background.
There has been considerable debate about whether patients with early-stage pancreatic cancer should undergo immediate surgery or receive neoadjuvant chemotherapy, Gaddam said.
“There’s been a shift toward neoadjuvant therapy but, for stage I disease, that is not clear,” he added.
Gaddam and colleagues had been evaluating the best approach to treat stage I disease when they posed another question.
“How do you know they’re truly stage I?” he asked. “Do we know that for a fact?”
Methods and results
Researchers used the National Cancer Database to identify all patients diagnosed with clinical stage I or stage II pancreatic ductal adenocarcinoma who underwent surgical resection between 2004 and 2020.
The cohort included 24,260 individuals with clinical stage I disease (mean age, 68 years; 51% women) and 23,850 with stage II disease (mean age, 66 years; 53% men).
Overall, 78.4% of patients originally diagnosed with stage I disease got upstaged following surgery, and 29.2% with stage II disease got upstaged after surgery.
“We know that early staging wasn’t great just from clinical experience, and I think most clinicians have an intuition about it, but we were surprised by the magnitude,” Gaddam said.
Technologic difficulties
Gaddam detailed two primary implications of these findings.
First, treatment decisions differ based on stage. Individuals diagnosed with stage I disease would possibly be better candidates for upfront surgery.
Second, if staging inaccuracies are indeed this prevalent, clinical trials enrolling patients who may have stage I or stage II disease may also have been staged inaccurately, thus limiting the clinical applicability of these studies.
“If [people with] stage I disease enrolled in these studies aren’t truly stage I, then it begins to question the validity of the studies we rely upon for clinical decision-making,” Gaddam said.
Technologic inadequacies make it difficult to properly stage patients, Gaddam said.
Stage IA, IB and IIA are all based on tumor size, and stage IIB encompasses all those stages if lymph node involvement is detected.
MRI, endoscopic ultrasounds and CT scans can miss both the tumor itself and if the lymph nodes are impacted. This is “what’s driving this upstaging,” Gaddam said.
Different imaging techniques are being investigated around the U.S., and some are trying to use AI to identify tumors and lymph nodes more accurately, Gaddam said.
“The game changer would be if we’re able to detect disease early by a simple, easy, inexpensive screening test,” he added. “When you search Google, you can find a lot of these tests, but they’re not ready for use yet. There are a couple that are interesting, but their accuracy is not high for pancreatic cancer yet. Those are the kinds of tests that will start tipping the needle in favor of early diagnosis.”
‘It won’t come quick’
Not much can be done to rectify improper staging currently, Gaddam said.
“Accurate staging is a building block for everything that happens to the patient afterward,” Gaddam added. “We know that this is a shaky part, and that we need to work on innovations in this area. It won’t come easy, it won’t come quick, but it will come.”
Gaddam encouraged radiologists, interventional gastroenterologists, pancreatic surgeons, and oncologists to dedicate as much effort as possible to lymph nodes, both in evaluating imaging and biopsies, and discussing treatment with tumor boards.
Additionally, more research is needed to investigate survival differences between patients who are improperly staged and those who are accurately staged, and evaluate treatments based on accurately staged patients.
Some members of the pancreatic cancer community have discussed treating all patients as if they have lymph node involvement given stage I disease is so rare, Gaddam said.
“I don’t know if we can make that conclusion based off our data, because no study is perfect, but I can tell you that’s a great thought,” he said. “Some of the thought leaders and reviewers have commented on that before. I don’t know the answer to that. It’s a really great point. There are people suggesting that most patients that we diagnose today as stage I should probably undergo neoadjuvant chemotherapy before surgery, because they’re likely to be stage IIB. I want to see follow-up studies in this area before drawing any conclusions.”
For more information:
Srinivas Gaddam, MD, MPH, can be reached at srinivas.gaddam@cshs.org.
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