Emil Lou, MD, PhD
DISCLOSURES January 07, 2026
Hi. I’m Dr Emil Lou, medical oncologist and specialist in gastrointestinal cancers at the University of Minnesota. It’s my pleasure to be here today to talk about all things, updates, and advances in pancreas adenocarcinoma.
There are about 45,000 new cases of pancreatic cancer in the US each year, about half of which are stage IV at the time of diagnosis. Stage means how far cancer is from where it started, and stage IV can include places like the liver, lungs, and bone — more or less in that order — or the abdomen, which are kind of the favorite sites of metastatic spread of pancreas adenocarcinoma.
For many years, over the past decade to decade and a half, we’ve been familiar with terms like FOLFIRINOX and combination chemotherapy with gemcitabine and nab-paclitaxel. This remains in place, but what’s coming down the pike in the months and years to come? Especially in this era of comprehensive genomic profiling, what implications might that have for treatment and how clinical decision-making, compared to today, can be different tomorrow and beyond?
I’ll first tackle the issue of chemotherapy and how it’s commonly used in both the metastatic setting and in the upfront setting for when there are cases called borderline resectable or locally advanced pancreas carcinomas, in which there’s an attempt to convert them from being unresectable or potentially on the border of being resectable to a more outright resectable. We know that surgical resection is crucial for any intent-to-cure strategy.
Unfortunately, only 10%-15% of all pancreas adenocarcinomas present with resectability at the time of diagnosis, but the paradigm has clearly changed in the past decade. The older paradigm, going back 10-20 years, was surgery followed by up to 6 months of adjuvant or postoperative chemotherapy intended for risk reduction, and usually that comprised gemcitabine.
There have been other studies looking at different combinations when surgery is performed upfront for those limited cases that are resectable at the time of diagnosis. We’ve seen the spectrum of combination therapies become superior to single-agent gemcitabine, namely gemcitabine with oral capecitabine; and subsequent groups from the PRODIGE consortium came out with FOLFIRINOX, which remains a standard of care. Much of the paradigm has shifted to more and more neoadjuvant intent therapy.
In general across the spectrum of different cancers, not just in pancreas adenocarcinoma, the intent of neoadjuvant therapy is multifold. It’s to increase the chance of R0 resection — in other words, no evidence of carcinoma at the surgical margins. Of course, we want surgical margins to be negative, and we want to try to diminish the chance that micrometastatic disease might blossom at distant metastatic sites and become stage IV before chemotherapy can take hold and manage that.
Also, many studies over time have shown such a high complication rate from the very in-depth and intensive form of surgery needed to adequately remove pancreas tumors, whether it be Whipple or, for more distant pancreatic tail tumors, similarly complex surgery and complication rates upwards of 40%.
Doing chemotherapy in part or total neoadjuvant therapy leading up to surgery, for as much as 6 months, has started to improve that condition, but we can always do better. The 5- or 10-year survival rate has just inched up toward, but has not really exceeded, 10%, and that survival rate is something we clearly need to improve upon.
In the era of genomic profiling it’s more widespread; it’s more democratic and openly accessible well outside of academic centers. We can get turnaround in as little as 10-14 days when tumors or biopsy specimens are sent out for genomic profiling. Of course, we can get information on hundreds of genes, but in terms of actionability or identification of targetable or actionable mutations for which there are drugs that fit the identified target, this is not as prevalent. They are few and far between.
I often quote to my patients that currently — and I hope this number changes in the months and years to come, based on well-designed clinical trials — the chance that the genomic profile would uncover information that would change clinical decision-making in the first line, second line, or beyond is well under 10%. It’s not yet in prime time, so to speak, for first-line therapy.
When we think of the results of the POLO trial that examined the 2% or 3%, approximately — not more than that — of patients who have alterations of the BRCA2 gene, for example, the drug olaparib, a PARP inhibitor, has been FDA-approved for maintenance therapy following first-line initiative therapy for patients who have a germline form of BRCA alteration.
We associate BRCA with ovarian or breast carcinoma most often, but there is a percentage of the population — again, well under 5% — with pancreas adenocarcinoma that is germline-variant. The way we target that is to offer PARP inhibition, as shown through the POLO trial, as a substitute for chemotherapy.
That trial examined vs placebo, so that’s not really what we do in routine standard of care, but it provides an opportunity for a chemotherapy-free interval, allowing a patient to have active cancer-directed therapy without a potential long-term cumulative cytotoxicity that comes with chemotherapy —for example, when gemcitabine and nab-paclitaxel are given in the first-line setting, or a platinum agent, olaparib, or others.
That’s an example of targeted therapy that we’re vastly trying to improve upon. The tumor stromal ratio and the other factors in pancreas carcinoma, and the dense — what we call desmoplastic — reaction produce especially strong challenges for the treatment of pancreas cancer and how chemotherapies and other drugs may penetrate the hard shell that pancreas cancer creates for itself.
It’s quite different from other gastrointestinal cancers and certainly different from other cancers in other parts of the body, and different from other adenocarcinomas in general. These are part of the challenges we’re finding.
On the tip of everyone’s tongues — clinicians, patients, and caregivers alike — is immunotherapy. With the immuno-oncologic revolution of non-small cell lung cancer and melanoma, of course, everyone will ask about immunotherapy. Certainly, not for lack of trying, the prevalent immuno-oncologic biomarkers, PD-L1 and others, are not yet ready in terms of having any discernible alteration in clinical decision-making or approving superiority or efficacy whatsoever in immune checkpoint inhibition.
The paradigms are changing and there are trials underway looking at LAG-3 and other types of potential checkpoints; and there are even checkpoints inside the cell, not just the ones on the surface of the marker, that are also actionable in different ways.
We think of microsatellite instability or deficient mismatch repair, for which there are tumor-agnostic indications to use pembrolizumab or other similar immune checkpoint inhibitors. The prevalence is also under 5%. The barrier we have is not for lack of want to, but some of the lack of efficacy is paired with the lack of prevalence compared to other cancers.
Certainly, tumor mutation burden, when present, if it is high and meets the FDA-approved criteria for 10 mutations per megabase, can open up new doors to the use of immune checkpoint inhibitors for patients in need.
For clinical trials, I would argue that more than any other cancer — maybe glioblastoma is the other one — we really have to think from the moment of diagnosis as clinicians whether there are any available. How can we help patients? Not just to move the needle for the overall patient population, but also to consider whether it would help individual patients who might be eligible, who are interested in cutting-edge, innovative trials, and consider either bringing these trials, opening them up, and translating them at our own centers or referring to larger centers where such trials might be available for patients especially motivated to participate.
When we consider the array of clinical trial opportunities, comprehensive genomic profiling has become more egalitarian and more available. Even if that prevalence is low of actionable alterations, which would include NTRK fusions and others that are tumor agnostic, FDA-approved indications, even if the percentage is only in the single digits, percentage-wise, it absolutely has become standard of care in 2025 and beyond to do genomic profiling, to offer it, to offer cancer genetics risk management and counseling for such patients in whom the germline alterations may be 10% or less, or hereditary potential causes that may be of interest to patients or caregivers. All of this allows whole care.
Now, I would be remiss if I didn’t mention the opportunity — and per the American Society of Clinical Oncology, the mandate for well more than half a decade — to offer all patients with newly diagnosed pancreas carcinoma opportunities to meet with palliative care specialists and really overcome that misnomer that palliative care means hospice. It does not.
It’s an all-encompassing, very proactive approach to helping patients manage the symptoms of their cancer, the side effects of therapy, very much including chemotherapy, and overall coping with a new diagnosis of cancer. This is helpful not just to patients but also their caregivers.
Over our short time together, I hope I have provided a brief overview of state-of-the-art treatment for pancreas adenocarcinoma and understanding the diagnosis — where we are now and, most importantly, where we’re going.
If I have the opportunity in the years to come to revisit this with you, I hope that I will be able to share updated clinical trials that have moved the needle, that improve that 5-year survival well past 10% and beyond, and that we can talk more about how advances in other cancers can be mirrored in helping our patients with pancreas adenocarcinoma.
