The first 60 days: Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma
Mismatch repair deficient pancreatic cancer is the rare pancreatic cancer whose cells cannot fix spelling errors in DNA and so carry thousands of mutations. That makes it one of the few pancreatic cancers that immunotherapy works against, and pembrolizumab is approved for it, though fewer of these tumours respond than in bowel cancer; testing every pancreatic cancer for the defect is the point. Below, week by week, is what OnCo's record of Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Testing.
- SurgeonNamed in the standard of care for: Resectable.
- Medical oncologistNamed in the standard of care for: Advanced, first line, Advanced, after chemotherapy, Resectable.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Surgery and adjuvant chemotherapy as for other pancreatic adenocarcinoma; neoadjuvant immunotherapy only in trials.
Mismatch repair immunohistochemistry or microsatellite instability testing for every pancreatic adenocarcinoma at diagnosis, with germline testing for Lynch syndrome when deficient.
Chemotherapy as for other pancreatic adenocarcinoma; pembrolizumab first line for patients unfit for chemotherapy or in trials.
Pembrolizumab (tumour-agnostic approval, KEYNOTE-158 pancreatic cohort) or dostarlimab (tumour-agnostic approval for mismatch repair deficient solid tumours).
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Mismatch repair protein immunohistochemistryor sequencing-based microsatellite instability testing on every pancreatic cancer, Tumour mutational burden, Germline Lynch syndrome testing when the tumour is deficient, KRAS statusand medullary or colloid histology, CA 19-9 for response monitoring), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include Lynch syndrome-associated mismatch repair deficient PDAC, Sporadic mismatch repair deficient PDAC, Medullary or mucinous colloid carcinoma of the pancreas.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Testing
- For my situation (testing), which of the standard options do you recommend and why?Guideline options include: Mismatch repair immunohistochemistry or microsatellite instability testing for every pancreatic adenocarcinoma at diagnosis, with germline testing for Lynch syndrome when deficient.
Advanced, first line
- For my situation (advanced, first line), which of the standard options do you recommend and why?Guideline options include: Chemotherapy as for other pancreatic adenocarcinoma; pembrolizumab first line for patients unfit for chemotherapy or in trials.
- Am I a candidate for FOLFIRINOX / mFOLFIRINOX, Gemcitabine + nab-paclitaxel, Pembrolizumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Advanced, after chemotherapy
- For my situation (advanced, after chemotherapy), which of the standard options do you recommend and why?Guideline options include: Pembrolizumab (tumour-agnostic approval, KEYNOTE-158 pancreatic cohort) or dostarlimab (tumour-agnostic approval for mismatch repair deficient solid tumours).
- Am I a candidate for Pembrolizumab, Dostarlimab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Resectable
- For my situation (resectable), which of the standard options do you recommend and why?Guideline options include: Surgery and adjuvant chemotherapy as for other pancreatic adenocarcinoma; neoadjuvant immunotherapy only in trials.
- Am I a candidate for FOLFIRINOX / mFOLFIRINOX, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of PRODIGE 24 / CCTG PA6 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Nivolumab, Ipilimumab, Dostarlimab, Off-the-shelf cancer vaccines?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “Response rates to PD-1 blockade are lower than in colorectal cancer and the reasons are not settled”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Whether checkpoint inhibitors should replace chemotherapy first line is untested in the pancreas”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma: the full pageMismatch repair deficient pancreatic cancer is the rare pancreatic cancer whose cells cannot fix spelling errors in DNA and so carry thousands of mutations. That makes it one of the few pancreatic cancers that immunotherapy works against, and pembrolizumab is approved for it, though fewer of these tumours respond than in bowel cancer; testing every pancreatic cancer for the defect is the point.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Neoantigen: A protein fragment created by a tumour mutation that the immune system has never seen before, so it can attack it without harming normal cells.
- Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR): The 'normal' result on the mismatch-repair test: the tumour has intact DNA spell-checking and few mutations.
- Germline vs somatic mutations: Germline mutations are inherited and in every cell; somatic mutations arise in the tumour only.
- Lynch syndrome: Lynch syndrome is the most common inherited cancer syndrome: a faulty mismatch-repair gene raises lifetime bowel cancer risk to 40-80% and also endometrial and other cancers.
- Tumour mutational burden (TMB): How many mutations a tumour has.
- Whipple procedure (pancreaticoduodenectomy): The big operation for cancers of the head of the pancreas: the surgeon removes the pancreatic head, the duodenum, the gallbladder and part of the bile duct, then reconnects everything.
- Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR): Microsatellite instability is the mark of a broken DNA spell-checker (loss of MLH1, MSH2, MSH6 or PMS2) that leaves thousands of mutations, so the tumour displays abnormal proteins that T cells can recognise.
Every term links to the glossary.