Standardizing endometrial cancer care with ProMiSE

Until recently, the way the medical system categorized endometrial cancers was fraught with challenges.

Patients were classified depending on how their tumours looked under a microscope — a system that works well for some cancers, like ovarian cancer, but was inconsistent for endometrial cancer. As a result, the same endometrial cancer patient could receive two different diagnoses and treatment plans, depending on which pathologist interpreted their results.

That has now changed, thanks to an innovative tool called ProMiSE (Proactive Molecular Risk Classifier for Endometrial Cancer) developed by Dr. Jessica McAlpine — professor and gynecologic oncologist at the University of British Columbia (UBC) and the BC Cancer Agency, as well as a Tier 1 Canada Research Chair — and her team in British Columbia.

Made possible through funding from the Michael Smith Health Research BC Innovation to Commercialization (I2C) program, the tool identifies molecular subtypes of endometrial cancer.

Specifically, ProMiSE uses pragmatic methods to assess molecular features and provide consistent pathological classification, which allows endometrial cancer patients to be assigned to one of four prognostic subtypes. The molecular subtypes also inform what treatments might be more effective for each patient and identifies which patients do not require additional therapy after surgery. Most of the methods are simple and can be done in any cancer centre, like testing for the presence of proteins in tissue, also known as ‘immunohistochemistry’ (IHC).

During the first phase of the I2C grant, McAlpine and her team worked with a Vancouver-based company (now called Imagia Canexia Health) to add a critical component of the molecular classification tool into an already approved gene panel used at Vancouver General Hospital (VGH). This component was POLE mutation testing. Patients identified with POLE have excellent outcomes and can be offered less treatment or even no treatment after hysterectomy surgery.

To demonstrate the need to standardize care for endometrial cancer, McAlpine’s team also conducted a study to analyze how patients across Canada were managed, including how they were diagnosed and the treatments they received, such as surgery, chemotherapy and radiation. The team looked at over 1,100 cases across 33 cancer centres and community hospitals. They compared the treatment patients received with traditional care to how they would have been managed if molecular subtyping had been performed.

“There were tremendous variations in clinical practice,” says McAlpine. “Knowing the molecular subtype would have dramatically changed clinical management. Forty-five per cent of people identified to have POLE mutated endometrial cancer received more treatments than they needed, and another 45 per cent of patients later identified to have an aggressive molecular subtype were given less therapy than we would recommend today.”

The team continued to advance ProMiSE during the second phase of I2C funding.

In 2020, they worked again with Imagia Canexia Health to simplify testing with a one-assay solution that looks for key mutations (like POLE and TP53) and assesses mismatch repair status with a special test called a microsatellite instability (MSI) assay. This harmonized testing strategy provides an important option for centres that do not have routine IHC testing and might otherwise not be able to provide ProMiSE classification for patients.

The momentum behind ProMiSE molecular classification continues to grow. Importantly, through funding from I2C and other sources, ProMiSE is now available for free for all newly diagnosed endometrial cancer patients in BC.

“Now in BC, no matter if you are from Fort St. John or Vancouver, you can get the same tests done if you are diagnosed with endometrial cancer,” says McAlpine. “It is a much more objective and reproducible series of tests that are less vulnerable to bias. It completely changes how someone is triaged after their diagnostic biopsy, how they are managed before and at surgery, and what is done after surgery for treatment.”

Work undertaken during the I2C grant also paved the way for an international clinical trial led by McAlpine and Dr. Kathy Han, medical oncologist at Princess Margaret Cancer Centre in Toronto, Ontario. The trial, currently underway, evaluates the safety of de-escalated therapy in patients with POLE mutated and other molecularly defined low-risk cancers.

“The Health Research BC grant provided tremendous momentum for this change in our province and across Canada,” says McAlpine. “The impact ranges from providing access to a critical component of this test for routine care to ensuring clinical trials can be available for our patients. Now that we know about the advantages of a subtype-specific approach in endometrial cancer management, it is just so important to get these tools to patients so they can have a more personalized medicine approach to their cancer.”

In addition to the funding from Health Research BC, McAlpine and her team also received support from the Canadian Institutes of Health Research (CIHR), the Canadian Cancer Society Research Institute (CCSRI), the BC Cancer Foundation and the VGH and UBC Hospital Foundations.