6 year survivor with a recurrence in peritoneum

@jwg19822005 Sorry to hear about the recurrence for your mom. It is great that you are pursuing the best treatment options available. How did the visit with surgeon go yesterday?

I would strongly support what you're already doing: get opinions from surgeons who specifically treat peritoneal disease and pancreatic cancer before assuming systemic chemotherapy is the only option. Her history is unusual—six years from diagnosis, long disease-free intervals, apparently very limited peritoneal disease, excellent performance status, and strong prior response/tolerance to FOLFIRINOX.

On the question about chemotherapy reaching the peritoneum: there is some scientific basis for that concern, but saying systemic chemotherapy simply “doesn't reach the peritoneum” is too strong. FOLFIRINOX and gemcitabine/nab-paclitaxel can and do produce responses in pancreatic cancer with peritoneal metastases. However, the peritoneal cavity can be a difficult compartment to treat, and intraperitoneal approaches can produce much higher local drug exposure. This is one reason HIPEC, NIPEC and PIPAC are being investigated.

The important issue is that CRS/HIPEC is not currently standard treatment for metastatic pancreatic adenocarcinoma. The evidence is still based largely on small studies and very carefully selected patients. Recent reviews nevertheless report encouraging long-term outcomes in selected patients with isolated, low-volume peritoneal metastases who can undergo complete cytoreduction. Researchers emphasize that we still don't know which patients truly benefit compared with systemic therapy alone.

Your mother's situation is exactly the kind of unusual case where I think asking about this makes sense. Before making a major decision, I would want the specialists to determine whether that 1.8-cm PET-positive nodule really is pancreatic cancer. If technically feasible, biopsy or surgical/laparoscopic confirmation could be important. “Consistent with peritoneal carcinomatosis” on PET isn't the same thing as pathology-confirmed carcinomatosis—particularly when we're talking about essentially one PET-positive lesion and an otherwise clear scan.

I'd also ask about a staging laparoscopy and Peritoneal Cancer Index (PCI). Imaging can underestimate small-volume peritoneal disease. A surgeon considering cytoreduction needs to know whether this really is one or two isolated implants or whether additional tiny deposits are present.

Her germline ATM mutation is another reason I'd want a pancreatic cancer precision-oncology specialist involved. ATM affects DNA-damage repair and makes platinum sensitivity and clinical trials particularly interesting, although ATM does not have the same established pancreatic-cancer indication for PARP maintenance that germline BRCA1/2 does.

There is active research in this area, which reinforces that your questions aren't unreasonable. Current studies are evaluating cytoreductive surgery plus HIPEC in highly selected pancreatic cancer patients with peritoneal involvement, typically requiring favorable biology and disease that remains controlled with systemic therapy.

So I would go into the Cleveland Clinic and Dr. Bartlett consultations asking one central question: “Is this truly widespread carcinomatosis, or is this an oligometastatic/very-low-volume peritoneal recurrence that could reasonably be approached with curative-intent or prolonged-disease-control treatment?”

Given her unusually long history and limited apparent recurrence, I would absolutely want that question answered by more than one experienced team before closing the door on an aggressive approach.

@tomrennie thank you! The appointment with the surgeon was very encouraging. He is really interested in the uniqueness of mom’s case and thinks there are definite surgical treatment options. Right now planning to do a diagnostic laparoscopy in two weeks, with the option for CRS/HIPEC or PIPAC. So, we’ve got some decisions to make. Thank you!

@mcharlesfrancis thank you so much for that thoughtful and detailed response. We met with the surgeon yesterday. He is wonderful, very interested in mom’s case and what we’re planning to do is exactly what you suggested. He really did his homework on her and feels that her cancer biology is likely one that would be favorable for localized treatment with CRS/HIPEC, but like you said, acknowledged that we really don’t know because there’s not enough research yet. In his words, “this is pancreas cancer but it’s not behaving like pancreas cancer,” which is why he thinks there are surgical options for her, even though historically surgeons wouldn’t touch pancreas cancer metastatic to the peritoneum (and many still won’t).

We’re planning a diagnostic laparoscopy/staging in a few weeks, so we can get a better picture of the extent of disease (he doesn’t see anything other than the one nodule on PET, but acknowledges that sometimes PET doesn’t show all peritoneal disease). He said he could also just resect the nodule without HIPEC - but that HIPEC would be like “swinging for the fences trying for a home run.” 🙂 And like you said, we don’t even have biopsy-confirmed metastatic disease yet so need to know what this thing actually is (probably cancer but need to know for sure).

He’s experienced in both HIPEC and PIPAC and brought up PIPAC as a gentler option, which sounds appealing, but it seems to be used more as a palliative treatment and isn’t really intended to be curative - not that we’re really expecting a cure, but HIPEC seems like it could possibly offer longer disease control, at least within the peritoneum.

He also encouraged us to get a second opinion with Dr. Bartlett before he even knew we had one scheduled already, so that was kind of cool.

This will be a tough decision for my mom to make. HIPEC is a major surgery and she’s nervous just thinking about it, but also grateful to have options. We’ll see how it all plays out in the end, but it gives me hope to know that she has both surgical and medical oncologists who are willing to see the nuances in her case and go beyond standard of care.

@jwg19822005 It is nice to have oncologists present options. Options are good even if they are difficult options. You have the right attitude to understand that you have to see how things play out in the end. Do your homework, get second opinions, and make the best informed decision that you can. Let the process work for you. So is the second opinion your next step?

@tomrennie yes, that was the next step. We met with the second opinion surgeon yesterday and he had about the same recommendations, although he slightly favors doing some sort of systemic treatment before surgery, whether that is chemo or daraxonrasib. However, he said if the diagnostic laparoscopy truly just shows the solitary nodule, upfront CRS/HIPEC would be a very reasonable choice.
upfront CRS/HIPEC would be the best option.

Her medical oncologist can get daraxonrasib for her if she wants it. I am sort of inclined to wait for daraxonrasib because I know if she would start on this it could disqualify her from future clinical trials. My thinking is that it will be there regardless in the near future, so maybe save it for if disease would pop up in other places later? I’ve also read positive things about clinical trials targeting KRAS G12D, which is the KRAS mutation she has along with her ATM, so it would be nice to keep the door open for one of those.

She did just have Signatera testing that was negative, but I have read that with peritoneal mets, this can often be negative even in the presence of disease.

I’m really thankful she has options. The waiting and decision making is really taking a toll on her mental health.

@jwg19822005 The mental and emotional challenges can be as difficult as the physical to manage. What does she typically do to relax?