EvidenceResectable pancreatic ductal adenocarcinoma

Together with NORPACT-1 this left the neoadjuvant question for resectable disease open: FOLFIRINOX before surgery is not proven superior to alternatives, and the comparison against upfront surgery with adjuvant modified FOLFIRINOX is what PREOPANC-3 and Alliance A021806 are running.

The strongest human evidence that a cancer vaccine can make durable T cells in a tumour with few mutations; the randomised phase 2 IMCODE003 (260 patients, primary completion listed for January 2031) is the test of whether that translates into fewer relapses.

Upfront surgery followed by adjuvant chemotherapy remains standard for clearly resectable pancreatic cancer; neoadjuvant treatment belongs in trials or borderline disease.

Pancreatic cancer was thought to be immunologically inert because of its low mutation burden; this study showed that with the right vaccine platform its few neoantigens can still be targeted. It is the strongest human evidence so far that personalised cancer vaccines can generate durable, tumour-specific immunity, and it justifies the randomised trials now running in pancreatic cancer and melanoma. Benefit is not yet proven, because responders may simply have had more immunogenic tumours.

The best survival ever recorded in a pancreatic cancer trial, and the benchmark every perioperative trial (PREOPANC-3, Alliance A021806) and every adjuvant RAS inhibitor or vaccine trial (RASolute 304, IMCODE003) now has to beat or add to.

Neoadjuvant treatment is now the standard for borderline resectable pancreatic cancer, and PREOPANC is the trial guidelines cite; the follow-on PREOPANC-2 tested FOLFIRINOX in the same setting.

The stage shift the pancreatic cancer page quotes (about three in four surveillance-detected cancers at stage I) and the strongest argument for offering surveillance to every germline carrier found by universal testing, which the NHS does not yet do outside research.

The trial that made neoadjuvant treatment standard for borderline resectable disease and opened the still unresolved question for resectable disease, which PREOPANC-2, NORPACT-1, PREOPANC-3 and Alliance A021806 inherited.

It shows a KRAS ctDNA test can be run to clinical laboratory standards in this disease, and it quantifies the lead time a surveillance programme would gain.

Postoperative ctDNA marks a group that current adjuvant chemotherapy does not cure, the rationale for ctDNA-guided intensification trials.

A germline result is not the whole story: without loss of the second allele the tumour may not be repair-deficient, which is why tumour sequencing and, in trials, HRD signatures are read alongside.

The formal adoption of PRODIGE 24 into practice; every later debate about giving chemotherapy before rather than after surgery starts from this recommendation.

The driver count is a prognostic score in itself, and the allele matters: G12D is the pancreatic allele with the worst outlook and the one the new selective inhibitors chase.

Modified FOLFIRINOX is the adjuvant standard for patients who recover well from a pancreatic resection and can tolerate combination chemotherapy; gemcitabine-based regimens remain for those who cannot.

The first long-term evidence that surveillance in high-risk people finds operable cancers, and the source of the imaging features that trigger surgery in the CAPS recommendations.

It made subtyping possible on the archived tissue every hospital has, and it retired one of the four Bailey subtypes.

It quantifies how little DNA an operable pancreatic cancer sheds and why every serious early detection panel pairs DNA with proteins.

Family-history criteria miss nine in ten carriers, the finding that moved guidelines to offer germline testing to every patient.

Gemcitabine plus capecitabine became the adjuvant standard after resection and remains the option for patients unfit for modified FOLFIRINOX.

Gemcitabine plus capecitabine became the adjuvant regimen for patients unfit for modified FOLFIRINOX, and remains the comparator in European trials of adjuvant treatment.

ctDNA quantity, not just presence, grades prognosis, which is why trials now stratify by allele fraction rather than by a yes or no.

The first demonstration that molecular residual disease can be read in pancreatic cancer and that it moves months ahead of the scan.

Adjuvant chemotherapy is standard after pancreatic cancer resection; gemcitabine alone remains the option for patients who cannot tolerate combinations.

The APGI cohort became the backbone of the QCMG whole-genome and subtype papers; ATM's entry here is the origin of its place on today's germline panels.

Either regimen was acceptable adjuvant therapy in 2010, with gemcitabine preferred for tolerability; combination regimens (ESPAC-4, PRODIGE 24) have since superseded both.

The trial that made adjuvant gemcitabine standard in Europe and the control arm PRODIGE 24 and ESPAC-4 later beat.

The origin of the European position that adjuvant treatment means chemotherapy alone; CONKO-001, ESPAC-3, ESPAC-4 and PRODIGE 24 all built on it, and the role of radiotherapy remains contested (LAP07, PREOPANC).

This trial introduced a patient-centred composite endpoint and a drug that remained the backbone of pancreatic cancer treatment for a generation. Its small survival gain also shows how low the bar was, which is the context for the FOLFIRINOX and MPACT trials that followed.

The pylorus-preserving Whipple became the standard variant, and the 1980 follow-up is an early record of the exocrine insufficiency that still goes untreated in most patients today.

Every treatment on this roadmap is either a way to reach this operation, a way to make it work better, or a substitute for patients who cannot have it.