Why pancreatic cancer often goes unnoticed
Pancreatic cancer kills so quietly that doctors often can’t spot it until it’s too late. This disease acts like a hidden enemy in your body. It stays undetected until reaching advanced stages. Let me explain why doctors have such a hard time finding this cancer early enough.
Lack of early symptoms
This cancer earned its nickname as a “silent” disease. Patients show no warning signs in the early stages [1]. Most people don’t notice anything wrong until the tumour grows big or spreads to other organs [2].
Signs of the disease creep up slowly [3]. These gradual changes make it hard for patients to realize something serious is wrong. Many patients say their first signs were unclear. They felt back pain or stomach discomfort that came and went before becoming constant [4].
Symptoms that mimic other conditions
The signs of pancreatic cancer look just like other less dangerous health problems. Here’s what patients usually experience:
- Abdominal or back pain
- Jaundice (yellowing of skin and eyes)
- Unintended weight loss and poor appetite
- Nausea and vomiting
- Fatigue or unusual weakness
- New-onset diabetes [5]
Doctors can easily mistake these signs for other health issues. To name just one example, see autoimmune pancreatitis (AIP), a rare condition that looks just like pancreatic cancer [6]. Both these diseases show up in people over 50 with jaundice, weight loss, and mild stomach pain [6]. Research shows all but one of these patients who have surgery for suspected cancer actually have AIP instead [6].
Scar tissue around pancreatic tumours can hide the cancer and lead to wrong diagnosis [7]. This happens because biopsies might pick up inflamed tissue around the tumour instead of cancer cells [6]. Some pancreatic cancers also look very normal under the microscope with only small cell changes, which makes them hard to spot [6].
Deep location of the pancreas
The pancreas sits deep in your belly, right behind the stomach and under the liver [1]. This creates big problems for early detection.
Your doctor can’t feel or see tumours during regular checkups because other organs hide the pancreas [1]. Standard physical exams won’t reveal these tumours [2]. Even modern imaging tests struggle to show small tumours or early-stage cancers clearly [3].
The pancreas’s location causes more problems than just being hard to see. Symptoms don’t show up until tumours grow big enough to push against nearby organs [5]. By then, cancer cells have usually spread beyond the pancreas [4].
These three factors – no early warning signs, lookalike symptoms, and the hidden location – work together to delay diagnosis. That’s why pancreatic cancer remains one of the toughest enemies doctors face.
Biological reasons pancreatic cancer is hard to detect
Pancreatic cancer’s stealthy nature comes from more than just its hidden location in the body. The disease has unique biological traits that make it hard to catch early. These molecular and cellular features create extra barriers that prevent detection until the cancer has spread substantially.
Tumour shielding and desmoplasia
Pancreatic tumours have a remarkable protective shield called desmoplasia – dense fibrous tissue that surrounds and protects cancer cells. This desmoplastic reaction makes up 80-90% of the tumour’s volume [8]. You can think of it as the cancer building its own fortress.
This protective barrier contains dense extracellular matrix (ECM) components like collagen, hyaluronan, fibronectin, and specialized proteins [8]. Pancreatic stellate cells that change into myofibroblasts produce most of this dense tissue [8].
The tumour uses desmoplasia as protection in several ways. The dense tissue creates unusually high pressure inside the tumour that squeezes blood vessels [9]. Blood vessel compression blocks the paths needed to deliver drugs, which creates a physical wall that stops chemotherapy from reaching cancer cells [8].
The desmoplastic shield feeds cancer cells and helps them spread to other parts of the body [8]. Research shows that “This environment nourishes the cancer cells and facilitates invasive and metastatic potential” [8]. The shield’s collagen also triggers signaling pathways that stimulate tumour growth and progression [8].
Low immunogenicity of pancreatic tumours
The body’s immune system struggles to fight pancreatic cancer, which experts classify as a “poorly immune responsive cancer” [10]. These tumours create an environment that stops natural defenses from spotting and attacking cancer cells.
Several factors help the cancer evade immune detection. The dense tissue not only blocks drugs but also stops immune cells like CD8+ T cells and natural killer (NK) cells from getting through [11]. Cancer cells often reduce their Major Histocompatibility Complex (MHC) class I expression, which prevents T-cells from recognizing them [12].
The area around the tumour attracts cells that suppress the immune system, including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumour-associated macrophages (TAMs) [12]. These immune-suppressing cells show up even when the cancer first starts developing [12].
Pancreatic tumours that lose SMAD4 (about 55% of cases) have much less T-cell infiltration, making them a “poorly immunogenic disease subtype” [13]. Both cancer cells and nearby tissue release transforming growth factor β (TGF-β), which actively stops immune cells from working [12].
Aggressive tumour growth and early spread
The most concerning trait of pancreatic cancer is how quickly it spreads. Studies show that cancer cells can spread to other parts of the body even before the main tumour grows very large [14].
These tumours grow by invading nearby tissues, lymph channels, nerves, and blood vessels early [6]. Cancer cells gain the ability to move and spread through several methods, including epithelial-mesenchymal transition (EMT) [7].
The cancer spreads extensively even when primary tumours are tiny. About 30% of patients have cancer in their regional lymph nodes, while 64% of T1 primary cancers already affect lymph nodes [6]. A detailed study of removed pancreatic cancers found cancer in lymph nodes in 89% of cases, lymph node spread in 77%, cancer in pancreatic nerves in 92%, and nerve invasion outside the pancreas in 45% [6].
These tumours have a special relationship with nerves. They tend to grow along nerve pathways using molecular signals like neural cell adhesion molecules (NCAM) [6]. Doctors find free cancer cells in 20-40% of patients’ abdominal cavities, even during surgery to remove tumours [6].
These biological features explain why surgery alone rarely cures pancreatic cancer. Even though surgeons can operate on more than 20% of patients, “the possibility of cure is gravely limited by the extent of early or occult micrometastases” [6].
Why current diagnostic tools fall short
Doctors need effective diagnostic tools to detect pancreatic cancer early. Current methods have major shortcomings that delay diagnosis. This explains why pancreatic cancer remains one of the deadliest cancers, as doctors often find it at advanced stages.
No routine screening methods
Pancreatic cancer differs from breast or colorectal cancer because it lacks recommended screening protocols for the general population [15]. Several challenges create this problem. No single diagnostic test can definitively identify pancreatic cancer [15]. Doctors need a combination of imaging scans, blood tests, and tissue biopsies to diagnose it—and they usually order these tests only after symptoms appear [15].
The cancer has typically grown and spread to other organs by the time symptoms develop [15]. The American Cancer Society reports that available tests haven’t lowered this disease’s mortality rate [15]. Screening the general population isn’t practical because pancreatic cancer occurs less frequently, and we lack an accurate, cost-effective screening method [16].
Limitations of imaging tests
Advanced imaging technologies struggle to show pancreatic tumours clearly. Transabdominal ultrasound’s sensitivity remains poor, with unsatisfactory results in about 20% of patients due to bowel gas interference [3]. CT scans, the gold standard for diagnosis, miss up to 11% of ductal adenocarcinomas because tumours look too similar to surrounding tissue [3].
MRI matches multi-section CT’s sensitivity and specificity but faces problems from breathing and bowel movement artifacts [3]. CT and MRI both struggle to stage lymph nodes and show therapy response [17]. These limitations make it hard to determine tumour boundaries and whether surgery is possible, even with the latest imaging technology.
Blood markers like CA19-9 are not always reliable
CA19-9, the most studied pancreatic cancer biomarker, has major drawbacks. This marker shows 79-81% sensitivity and 82-90% specificity in patients with symptoms [18], but fails as a screening tool with only 0.5-0.9% positive predictive value [18].
CA19-9’s key limitations include:
- Lewis antigen-negative individuals (5-10% of patients) show false-negative results [18]
- Obstructive jaundice causes false positive elevations (10-60% of cases) [18]
- Other conditions like colorectal cancer, liver disease, pancreatitis, and biliary infection raise levels [19]
CA19-9 can’t tell the difference between benign conditions, precursor lesions, and malignant pancreatic diseases [2]. The National Academy of Clinical Biochemistry suggests using CA19-9 only with other diagnostic tools like CT or endoscopic ultrasound [2].
These diagnostic challenges lead to delayed detection, which makes answering the question “Is pancreatic cancer curable?” difficult for most patients.
Who is most at risk and why it matters
Learning about who has a higher pancreatic cancer risk is a vital pathway to detecting it earlier. This knowledge helps doctors monitor high-risk patients and might answer whether pancreatic cancer becomes curable with early detection.
Genetic mutations and family history
Hereditary factors contribute to about 10% of all pancreatic cancer cases [1]. Your risk increases 2.1-5.3 times if you have a first-degree relative with pancreatic cancer [20]. The risk grows even more with multiple affected family members—from 4.5 times with one relative to 32 times with three or more relatives [20].
Specific gene mutations add to this inherited risk. BRCA2 mutations lead to a 3-8 times higher risk [21], while CDKN2A mutations create a 13-22 times higher risk [21]. Other genetic syndromes that raise the risk include:
Lifestyle-related risk factors
Lifestyle choices play a big role in pancreatic cancer risk. Cigarette smoking tops the list, causing 20-30% of all cases [5] and doubles the risk compared to non-smokers [5]. The good news? Risk drops to normal levels after 20 years of quitting [4].
Extra body weight also raises your risk. People with obesity (BMI ≥30) are 20% more likely to develop pancreatic cancer [23]. More than 10% of pancreatic cancers in the UK link to being overweight or obese [4].
Chronic pancreatitis, often caused by heavy drinking, increases the risk too [23]. The risk jumps tenfold in people who smoke and have diabetes plus one affected first-degree relative [20].
New-onset diabetes as a warning sign
The link between new-onset diabetes and pancreatic cancer reveals interesting patterns. About 25% of pancreatic cancer patients develop diabetes within three years before their cancer diagnosis [24]. This relationship works both ways—diabetes can cause pancreatic cancer and be caused by it.
People with new-onset diabetes and a family history of pancreatic cancer face a 3.78 times higher risk than others [25]. A quick rise in blood glucose levels means a 2.33 times greater risk [25]. Some patients lose weight unexpectedly around diagnosis [26]—in stark contrast to this, type 2 diabetes usually causes weight gain.
Doctors can use these risk factors to identify patients who need closer monitoring. This approach might lead to better outcomes for this challenging disease.
Can pancreatic cancer be cured? What the future holds
Pancreatic cancer research has made breakthrough discoveries that bring hope to an otherwise challenging field. The five-year survival rate has reached 13% in 2024 [8], and new advances in detection and treatment methods continue to improve patient outcomes.
Emerging treatments like immunotherapy and vaccines
Immunotherapy shows great promise, especially for patients with microsatellite instability (MSI) or mismatch repair deficiency (dMMR) – about 1-3% of cases [9]. The FDA has approved treatments like pembrolizumab (Keytruda) and dostarlimab (Jemperli) for these specific tumour types [27].
Therapeutic vaccines are opening up new possibilities in treatment. These vaccines work differently from preventive ones – they help the immune system identify and fight existing cancer cells. The mRNA vaccine autogene cevumeran has shown encouraging results. Half of the tested patients developed an immune response, and six out of eight responders stayed cancer-free during the follow-up period [28].
Liquid biopsies and early detection research
Early detection makes a huge difference in survival rates. Patients diagnosed in the earliest stages have a 44.3% survival rate compared to just 3.2% for those with metastatic disease [29]. Scientists have developed a groundbreaking exosome-based liquid biopsy that works with CA19-9 testing. This combination accurately finds 97% of stage 1-2 pancreatic cancers [29].
Improved survival rates with combination therapies
Combination treatments have helped patients live longer. Using nab-paclitaxel with gemcitabine extends median survival to 8.5 months, up from 6.7 months when using gemcitabine alone [30]. Adding elraglusib to this combination has shown even better results [31]. The FDA’s recent approval of NALIRIFOX gives doctors another effective first-line treatment option [8].
Conclusion
Pancreatic cancer stands as one of medicine’s toughest challenges because it grows silently until it reaches advanced stages. Its deep location in the body, absence of early warning signs, and biological traits like desmoplasia and early metastasis create the perfect storm for late diagnosis. Our current diagnostic tools make early detection even harder.
Knowing the risk factors is vital if you have higher chances of developing this cancer. People should definitely talk to their doctors about proper monitoring if they have genetic risks, family history, smoking habits, obesity, or newly diagnosed diabetes. While pancreatic cancer affects a small portion of people, its devastating effects make increased watchfulness necessary and with good reason too.
New developments give us room for careful hope. Some patients respond well to emerging immunotherapies, and therapeutic vaccines might be a game-changer. Liquid biopsies and better combination treatments also show promise for improving patient outcomes. The five-year survival rate sits at 13% – still low, but all the same, it has improved as time passed.
Better outcomes depend on more research funding and greater awareness. Early-stage pancreatic cancer shows substantially better survival rates, though it’s rarely caught early. This highlights why we need better detection methods. Until we can screen everyone effectively, spotting risk factors and warning signs helps us catch this sneaky disease earlier. While pancreatic cancer might never be easily curable for everyone, improved treatments and earlier detection will without doubt save many lives we once thought were beyond help.
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