Using the PREMM5 Model for Lynch Syndrome Screening in Colorectal or Endometrial Cancer

Abigail Zamorano, MD, MPHS, University of Texas Health, Houston, Texas, discusses a pilot study done to evaluate a Lynch Syndrome predictive model at the LIGA-INCAN cancer hospital in Guatemala City, Guatemala. The PREdiction Model for gene Mutations (PREMM5) is a clinical algorithm to evaluate a patient’s risk of carrying a Lynch Syndrome mutation, developed with a low-resource setting in mind.

This study found the PREMM5 model to be a feasible tool for identifying patients at risk of carrying mutations associated with Lynch Syndrome. As Dr Zamorano stated, “In the setting where resources are scant, [the PREMM5 model] might better help us determine who really needs that testing, and then how could we prevent then future cancers down the line.”

Transcript:

Hi, I'm Abigail Zamorano. I am an assistant professor of gynecologic oncology at UT Health in Houston. And I'm going to be talking about a study that we did with our partners at INCAN Hospital in Guatemala City, on the use of the PREMM5 model to screen for patients at risk for Lynch Syndrome.

This was a cross-sectional pilot study that we concluded at INCAN Hospital in Guatemala City. INCAN Hospital is the only hospital to provide complete oncologic care to underserved or uninsured Guatemalan citizens. So it was a really valuable place to study cancers that can affect a large portion of the population. Right now, we don't have any information in Guatemala on the rates of Lynch Syndrome and we have very little information even on the rates of colorectal cancer and endometrial cancer.

Lynch Syndrome is a genetic syndrome that makes patients or individuals more at risk for certain types of cancers, notably colorectal cancer and endometrial cancer. The standard of care in many developed countries is genetic testing or at least tumor testing, molecular testing, of patients with endometrial cancer or colon cancer. However, many developing countries don't have the resources to pursue this. Guatemala is one of those countries where many patients, even though they may be diagnosed with one of these cancers, they don't have the resources to undergo the molecular testing which would say that they may or may not be at risk for Lynch syndrome, and then they don't have the resources for the genetic testing.

We sought to find out if there could be a way for us to screen individuals that had been diagnosed with colorectal or endometrial cancer to better predict their likelihood of having Lynch syndrome. Right now, INCAN does not have the ability to provide genetic testing to patients, but we sought to provide some initial information so that hopefully genetic testing will be available to patients in the future, because this is so important.

I should say that this is so important because once a patient has a diagnosis of Lynch Syndrome, even if they already have a diagnosis of say colon cancer or endometrial cancer, they could then undertake measures to prevent other types of cancers that may be associated with Lynch Syndrome. They could also inform their family members about their diagnosis so that future cancers could also be prevented.

As I said, we conducted a cross-sectional pilot study of 50 patients, 25 with colon cancer and 25 with endometrial cancer, who had been treated at INCAN. This was a phone-administered survey by our partners at INCAN. They called patients who had been treated at the hospital and obtained verbal consent and then administered the PREMM5 survey. The PREMM5 survey is a combination of personal questions regarding their own cancer diagnosis, as well is questions on the patient's family and various family members and whether those family members had been also diagnosed with any type of cancer and what type of cancer.

Patients completed the PREMM5 survey. They then also completed a short survey asking how they felt completing the PREMM5 survey if they found that it was easy to complete, if they found that they recalled the information about themselves and their family members easily, and if they had any if they had any questions about it and also if they understood the process.

We also importantly ask patients if they were both interested in and then available to undertake further preventative measures, depending on any sort of genetic results — meaning if they were found to have Lynch Syndrome, would they be interested in having increased colon cancer screening or having a hysterectomy? Would they be able to complete any of those things? Our aim was to not only determine the predicted probability of Lynch syndrome in this population, but also to determine the utility of this information.

We found that 62% of patients who completed the PREMM5 model with us had at least a 2.5 % predicted probability of Lynch syndrome. This is over the threshold for which genetic testing is recommended. We found that almost all the patients found the survey easy to complete and that they thought that it was very easy to recall both personal and family medical information. They also understood its purpose and reported an interest in and ability to act on the results if possible.

This is really important information because our goal is that we could potentially use the PREMM5 model in underserved or under resourced areas to better choose which patients should undergo genetic testing. In an ideal world, everyone would have molecular testing or genetic testing, but in the setting where resources are scant, this might better help us determine who really needs that testing, and then how could we prevent then future cancers down the line.

We're hopeful that this information can be distributed to patients and providers in other such locations, and we are very excited about our results. We think that they show great promise in the field of both colon cancer treatment, endometrial cancer treatment, as well as genetic counseling.

Source:

Bissmeyer MA, Velarde A, Salazar AS, Zamorano AS. Use and feasibility of a Lynch Syndrome predictive model for inherited colorectal and endometrial cancer in a low-middle income country. Familial Cancer. Published Online: September 24, 2024. doi: 10.1007/s10689-024-00422-y.