When pancreatic cancer patients receive chemotherapy or radiation before surgery (neoadjuvant therapy), the tumor tissue undergoes dramatic changes that make pathologic examination far more difficult. Extensive therapy-induced scarring (fibrosis) blurs the boundary between tumor and normal tissue, making it very hard to accurately measure tumor size or identify remaining cancer cells.
Currently, there are no internationally agreed-upon standard guidelines for how pathologists should examine these treated pancreatic specimens. Different hospitals use different approaches for grossing (cutting and preparing), sampling, measuring tumors, and grading treatment response — making it nearly impossible to compare results across institutions or clinical trials.
The Pancreatobiliary Pathology Society formed a dedicated working group in 2018 to address this gap, bringing together expert pathologists from Asia, Europe, and North America to develop consensus recommendations.
Seven expert pancreatic pathologists from three continents formed the Neoadjuvant Therapy Working Group. They systematically reviewed published literature, current grossing protocols from institutions worldwide, and existing grading systems for treatment response.
The group circulated draft recommendations to all 130 members of the Pancreatobiliary Pathology Society via a Society-wide electronic survey, collecting comments and votes on each proposed recommendation. Comments submitted by email or online were collated and incorporated into the final consensus.
This process ensured that the recommendations reflected the expertise and experience of pathologists internationally, not just a single institution's preferences, giving them broad applicability.
The working group recommends systematic, standardized grossing using consecutive mapping sections along the largest tumor dimension. After serial sectioning of the pancreas at 3–5 mm thickness, the largest tumor dimension should be identified grossly and confirmed microscopically — this combined approach is required by the College of American Pathologists cancer protocol.
For tumor size measurement, the recommendation is to measure microscopically as the largest dimension bounded by viable tumor cells, including intervening stroma (the supportive tissue). This addresses a key problem: after treatment, the gross (visible to the eye) tumor size is often misleading because of fibrosis.
Smaller treated tumors of 2 cm or less should be entirely submitted for microscopic examination. Larger tumors should be sampled generously with at least 2 sections per centimeter. If no gross tumor is visible, the entire pancreas and surrounding tissues should be submitted before declaring a complete pathologic response.
Two systems are commonly used to grade how well a tumor responded to preoperative therapy: the MD Anderson system and the College of American Pathologists (CAP) system. The working group recommends the MD Anderson system because studies show it correlates better with patient prognosis and has better agreement between different pathologists.
The MD Anderson system grades tumors on a scale based on the percentage of viable tumor remaining: Grade 0 is complete response (no viable tumor), Grade 1 is minimal residual tumor, Grade 2 is moderate response, and Grade 3 is poor response. Each grade has a meaningful difference in patient outcomes.
A critical recommendation is that a case should never be classified as complete pathologic response unless the entire pancreas, surrounding soft tissue, common bile duct, and duodenum adjacent to the pancreas have all been submitted for microscopic examination — a rigorous standard that prevents missing small residual tumor deposits.
Accurate pathologic assessment after neoadjuvant therapy directly influences postoperative treatment decisions, including whether additional chemotherapy is needed and which type. Inconsistent pathology reporting across centers undermines the ability to compare survival outcomes in clinical trials that evaluate new preoperative therapies.
The minimum requirement of examining 12 lymph nodes — standard in untreated specimens — applies equally to post-therapy specimens. Radiation can make lymph nodes harder to find grossly, but thorough dissection typically yields adequate numbers. Documenting when this minimum cannot be reached is itself a clinically important finding.
Standardized reporting also facilitates research: if all centers use the same grading and sampling approaches, pooled datasets become meaningful, accelerating discovery of factors that predict which patients benefit most from neoadjuvant therapy.
These consensus recommendations provide the first international standard for pathologic examination of post-neoadjuvant therapy pancreatic resection specimens. Adoption of these guidelines across centers worldwide will improve the comparability of research results and better guide individual patient care.
The working group acknowledges that evidence supporting some recommendations is limited due to the relatively recent adoption of neoadjuvant therapy for pancreatic cancer, and calls for future studies to validate and refine these standards. Particular attention is needed to develop reliable markers distinguishing cancer-associated fibrosis from therapy-induced fibrosis.
Ongoing collaboration between pathologists, surgeons, and oncologists — standardized by documents like this — is essential to translate improvements in neoadjuvant therapy into measurable survival benefits for pancreatic cancer patients.