The Impact of Early Diagnosis
Case Study: A 62-year-old man presented with a 4-month history of fatigue, vague abdominal discomfort and a 30 lbs unintentional weight loss. His past history was significant for ethanol abuse, hypertension, high cholesterol and type 2 diabetes and his medications included hydrochlorothiazide, rosuvastatin, metformin and ramipril. Bloodwork including CBC, lytes, creatinine and LFTs were all normal. U/S of the abdomen revealed a nonspecific gas pattern with no obvious significant abnormalities. Due to persistent symptoms, a CT abd/pelvis was arranged that identified subtle soft tissue changes in the region of the celiac axis. An MRI was performed to specifically evaluate the pancreas which confirmed a primary pancreatic lesion that might represent the sequelae of chronic inflammation although pancreatic cancer couldn’t be excluded. CA 19-9 was 87. He was referred to gastroenterology who performed upper and lower endoscopy and took brushings and washings of the pancreatic duct. All results were either insufficient for interpretation or negative for malignancy. His case was discussed at a GI multidisciplinary case conference and it was felt that the lesion could be consistent with a pancreatic cancer and that due to the presence of vessel involvement, would not be a surgical candidate. It was also deemed that the lesion could not be safely biopsied percutaneously and so he was referred for an endoscopic ultrasound and biopsy for diagnosis. This was ultimately performed but the sample demonstrated very little cellular material with some inflammatory cells and signs of atypia but no confirmation of adenocarcinoma or malignancy. During this time, his weight loss continued and his pain worsened.
Discussion: Pancreatic cancer continues to be a challenging tumour site. Early diagnosis is key to management as the only curative strategy involves surgical resection of the primary tumour. However, patients often have very few symptoms or have those that mimic more common, less dangerous conditions thus leading to a potential delay in the time to appropriate investigations and diagnosis. At present, there are no screening programs for pancreatic cancer due to the relatively low prevalence of the disease, challenging imaging characteristics and lack of a reliable identifiable biomarker.
As highlighted by the case example, making a diagnosis can be very challenging as patients often present with nonspecific symptoms and are already at a point where the disease has become too advanced for surgery. Imaging tests may not be able to reliably distinguish between chronic pancreatitis and malignancy and although the CA 19-9 is sometimes helpful, it can be elevated for both benign and malignant reasons and may even be normal in the setting of malignancy. Acquiring appropriate tissue sampling is also often a challenge particularly in the locally advanced setting as the primary site may be difficult to access for biopsy. This may lead to repeated attempts at biopsy and a delay in initiating treatment.
Patients with advanced disease are often managed in multidisciplinary settings with supportive care and palliative care forming a significant element of co-managed care from the outset. For motivated patients with good PS, multi-agent chemotherapy with FOLFIRINOX or Gemcitabine and nab-paclitaxel or enrollment on clinical trials if available are good options for initial therapy. Single agent gemcitabine still remains an option for some patients or those with poorer PS. While newer therapies such as the immuno-oncology agents have yet to show significant benefit, other agents that attempt to improve drug delivery and/or drug penetration into the tumour are showing promise. Examples include nanoliposomal irinotecan and PEGPH20. In addition, there is evidence from retrospective series now showing that effective use of first-line treatment leads to a greater likelihood of receiving second line therapy and a longer overall duration of treatment with improved OS. This highlights the importance of careful patient selection and treatment individualization to maximize outcomes.