Prostate cancer is the most common cancer in Canadian men, with more than 27,000 Canadians being diagnosed with the disease each year. In many cases, prostate cancer develops slowly and can be successfully removed or managed before it spreads to other parts of the body. However, like most types of cancers, there is a risk of prostate cancer to spread or recur after removal or treatment. Traditionally pathologists and clinicians determine cancer recurrence by manually analyzing different images or biosamples.

Matthew McNeil is a senior PhD student working in senior scientist Dr. Anne Martel’s lab at Sunnybrook Research Institute (SRI) where he is developing tools to support the automatic prediction of cancer recurrence. This fall, Matthew was the winner of the Leopard Challenge, a global AI competition. Specifically, the challenge focused on yielding deep learning solutions to predict the time to biochemical recurrence of prostate cancer from H&E-stained histopathological tissue sections.

Matthew is developing AI models that quickly detect features, like Gleason patterns, on slides that pathologists typically use to determine prognosis. The Gleason classification system is used to grade prostate cancer. The scale looks at how abnormal glands in the prostate look and helps determine how likely the cancer is to grow and spread.

“By having these types of patterns highlighted automatically, pathologists will be able to analyze slides more quickly and effectively,” explains Matthew. “My model also has the potential to provide clinicians and patients with a better understanding of the cancer’s risk.”

The model is capable of quickly generating risk scores for patients with prostate cancer. This has the potential to advance patient care and outcomes by supporting more personalized treatment plans as generating these scores can help both clinicians and patients make more informed care decisions.

Matthew is hoping to apply the model he developed during the Leopard Challenge to other datasets for different types of cancers and see his work expand to clinical settings.

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Research into an innovative new approach to screening patients for prostate cancer might mean faster answers and fewer biopsies are possible

It was hard for Leonard Forde to watch his family members get prostate cancer, one after the other.

So, when his doctor told him his own prostate-specific antigen (PSA) level had risen dramatically, which can indicate prostate cancer, he wasted no time.

Within weeks, he underwent a prostate needle biopsy at a hospital in downtown Toronto. Though he had a background in nursing and recognized the procedure’s importance in detecting cancer cells, Leonard found the procedure challenging.

“It was a bit humiliating,” says Leonard, who also experienced some discomfort and blood in his urine after the procedure. But within days, he had an answer: no cancer was present.

“It was a big relief,” he says.

Since that first needle biopsy 20 years ago, Leonard, now 74, has had three more. Once a year he sees a urologist, who checks his PSA levels and occasionally does a digital rectal exam. He’s also had MRIs to ensure he isn’t developing prostate cancer.

Though it isn’t always pleasant, the Stouffville, Ont., resident knows that staying on top of his prostate health is key to identifying – and surviving – prostate cancer.

“And medicine can only get better.”

It’s that type of thinking that’s driving researchers at Sunnybrook to improve the way they are identifying patients at high risk for prostate cancer, which affects 22,900 men a year in Canada, according to the Canadian Cancer Society. Sunnybrook is developing non-invasive tests with the aim of better flagging people who may have prostate cancer, without the need for everyone to undergo a traditional prostate needle biopsy.

The new approach would include a blood test that would look for specific biomarkers or proteins released by cancer cells, coupled with sophisticated imaging to assess how far a cancer has progressed. The focus is on preventing aggressive overtreatment of prostate cancer, says Hon Leong, PhD, a scientist with the Sunnybrook Research Institute.

“[Prostate cancer surgery] is one of the more serious surgeries a man can undertake,” Leong says. “We want to confidently say, ‘You have a high risk of cancer, and something needs to be done,’ or ‘You have a low-grade [risk] cancer and we don’t think you need surgery; treatment would be excessive.’”

While radical treatment, including surgery, for prostate cancer can often successfully remove all cancer cells, it comes with potential side effects. These can include bleeding and infection, sexual issues, such as erectile dysfunction, loss of bladder control and urine leakage.

The new, two-step approach to prostate cancer testing being investigated at Sunnybrook aims to ensure only the men who require radical treatment will receive it.

A state-of-the-art technique

In order to test out their new approach, Sunnybrook researchers, along with scientists at the Ontario Institute for Cancer Research (OICR), are recruiting for a clinical trial involving 1,000 men. They’re assessing the accuracy of a blood test developed by Leong and Karla Williams, PhD, called the PolySia liquid biopsy – a blood test that identifies PolySialic Acid, a sugar that’s expressed by cancer cells and released into the blood.

“This is the first [test] where we’re looking for specific types of sugars on the prostate cancer cells,” Leong says. “We’re looking at the behaviour of the cancer cells that you can’t see on imaging.”

This liquid biopsy could be very effective if used in tandem with imaging, such as an MRI, Leong says. “This is a very precise and accurate way of determining who should get the needle [biopsy],” he adds.

Dr. Christopher Lim, an abdominal radiologist at Sunnybrook, says the new approach has the potential to revolutionize the way prostate cancer is identified and screened.

“In the past, a man with a suspicious finding would go straight to prostate needle biopsy,” Dr. Lim says. “That’s changing.”

Given the accuracy rate of the PSA test, that’s good news. A PSA level of 10 nanograms per millilitre (10 ng/mL) and above means a person has a 50 per cent chance of having prostate cancer. A needle biopsy is usually ordered in this situation. Though PSA tests are the current standard of care to ascertain a patient’s risk of cancer, PSA levels are known to fluctuate, and high levels don’t always mean cancer is present.

“We know that blood tests that measure PSA are important, but it’s not always as effective as it should be,” Leong says.

Hon Leong at the Sunnybrook Research Institute. (Photography by Kevin Van Paassen)

Leonard knows about fluctuating PSA levels all too well. Over the past several years, his PSA level stubbornly hovers between 14 and 17 ng/mL, putting him in a high-risk category for developing prostate cancer.

Leonard would like to know the cause of his elevated PSA levels without having to undergo needle biopsies. During the procedure, doctors insert a needle through the wall of the rectum. Then, numerous tissue samples are collected from different areas of the prostate gland via the needle.

The idea is that taking tissue from disparate areas of the prostate should yield a representative sample of the prostate. In Leonard’s case, the tissue samples from each prostate needle biopsy – he’s had four – has showed no cancer cells when they were examined under a microscope.

Leonard says he had blood in the urine and painful urination and defecation after the procedures, but fortunately has never developed an infection.

The rate of infection from a prostate needle biopsy is between 0.1 per cent and 2 per cent, says Leong. The new “liquid biopsy” would help reduce this problem since fewer men would be getting needle biopsies.

“It would also decrease the time spent waiting for results,” Leong adds. He’s keenly aware that many patients would welcome earlier results. Tissue biopsies can take weeks before results are available, and patients are often very anxious, wondering whether they have cancer. Blood tests could provide answers the same day, sparing patients a lot of stress and worry, says Leong.

A blood test is also inexpensive and easy to obtain, because there’s no preparation time – and no enema required. “It’s a cheap, affordable way to monitor what’s happening,” he says.

“It helps alleviate the strain on the health-care system,” Dr. Lim adds.

Harnessing the power of artificial intelligence

The second part of the two-step process is an MRI that follows the blood test to help identify who actually has high-risk prostate cancer. These MRIs are also being improved by harnessing the power of AI, says Dr. Lim.

Although MRIs are used to identify abnormal areas of a prostate, researchers are working toward improving their sensitivity, he says. “We want more precise information from the MRI, [because] some features are not visible to the naked eye.”

Dr. Lim says that AI-powered research can identify certain characteristics that suggest malignancy. He likens the heightened sensitivity of these MRIs to looking more closely at a piece of clothing.

“If you look at a sweater, you [just] see the whole sweater,” he says. “But if you look very closely, you can see more, like the texture of the fabric and the pattern of the weave. It’s as if we are using a very precise digital microscope.”

The new, more intricate MRI would allow radiologists to get extra information, providing key data about the rate of tumour growth and aggressiveness. This would allow doctors to more effectively grade and stage the tumour, gaining better insights into which patients can avoid needle biopsy.

“It’s a two-step authentication. When you combine a liquid biopsy with intricate MRI, it allows us to get more information on who can safely avoid a needle biopsy,” Dr. Lim says.

Sunnybrook’s collaborative approach means the process will have support across many different departments in the hospital, he notes, which will be helpful in accelerating its adoption and success.

“Sunnybrook is an ideal place to do this research, because we have some of the world’s leaders in prostate diagnosis and management,” Dr. Lim says. “There’s a meeting of the minds.”

Leong says that after his team completes the first clinical trial employing the two-step authentication process, a second one will be necessary. Even so, should results be favourable, the combination of liquid biopsy and MRI (two-step authentication) could be available in as little as three years.

Leonard is buoyed by the news. Now that he lives with chronic prostatitis, a painful swelling and inflammation of the prostate gland, Leonard would prefer to avoid any procedures that involve sampling prostate tissue.

He says he likes the idea of screening for prostate cancer using just blood work and imaging, instead of undergoing needle biopsies. “It sounds much better than the other procedure,” he says.

Despite this, Leonard will continue to be screened regularly for prostate cancer. He’s also urged his family members to get screened as well.

Dr. Lim is confident that the thousands of men like Leonard, whose lives have been touched by the disease, will soon have an easier way to monitor their prostate health. “The management of prostate cancer is changing rapidly,” says Dr. Lim. “It’s exciting. And it’s happening here in Canada.”

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A clinical trial is a research study that involves people. After showing promise in a lab, a clinical trial is the next step. Clinical trials look at the effect of a medical action on people’s health and often compare one treatment to another. The studies often look at how well new treatments work and how safe they are to administer.

When it comes to prostate cancer — the most commonly diagnosed cancer in men — there are tons of trials with a wide range of focuses.

“There’s a trial available for every point of the prostate cancer experience – from detection to diagnosis to treatment and beyond. There’s a whole team here dedicated to this,” said Dr. Stanley Liu, a radiation oncologist at Sunnybrook. “These trials are looking for better ways to find prostate cancer, better ways to figure out whose cancer will be aggressive, and better ways to treat it at any stage.”

How can we see the cancer?

Many researchers are looking at how prostate cancer is detected and diagnosed. This type of trial might look at the use of imaging and what type of imaging can best see the cancer. Participants could be randomized to get one type of image or another.

Whose cancer will be aggressive?

Some men with low-grade prostate cancer may never go on to have an advanced form of the disease. But how can doctors determine who’s cancer will be aggressive?

“At Sunnybrook, we are involved in several trials that are looking at ways to determine who’s prostate cancer will be more aggressive – for example, looking at cells in urine to see if there’s signatures in there that indicate the cancer is more aggressive,” Dr. Liu said. This type of trial might involve blood tests, urine test or other samples being collected and examined.

How can we best treat prostate cancer? 

How you are diagnosed with prostate cancer and treated is based on many years of research, evidence and trials. Researchers constantly revisit that evidence to come and with better, safer ways to find and treat the disease.

A Sunnybrook-trial led to the widespread use of “active surveillance” for prostate cancer, where men with early stage disease are closely monitored rather than treated aggressively. The 15-year results were recently published by Drs. Andrew Loblaw and Laurence Klotz from Sunnybrook, and they demonstrated that this is a safe and effective approach to manage early stage prostate cancer. This key trial helped make active surveillance a standard-of-care in North America.

At Sunnybrook and around the world, researchers such as Dr. Loblaw have been looking at newer forms of radiation that target the tumours more precisely. One example of this is stereotactic body radiation therapy (SBRT),  where high levels of targeted radiation are given over a short period of time. This type of treatment is already used for other cancers. At Sunnybrook, we are involved in several SBRT trials, looking at if a shorter course of higher dose radiation (e.g., 5 days versus 20 days) can improve prostate cancer cure while minimizing effects on a patient’s quality of life. This would involve radiation treatments as well as surveys or interviews to help determine how your quality of life is after treatments.

How can we treat prostate cancer that comes back or is advanced?

These types of trials might add an additional chemotherapy drug or a targeted agent to the current standard of care (radiation, surgery or chemotherapy) to see if there are better patient outcomes.

How do I know if a trial is right for me?

At an academic health sciences centre, there are many options for trials. There is infrastructure in place to allow involvement with lots of trials. Some of Sunnybrook’s doctors are the lead investigators or the site leads on an international trial. Talk to your doctor for more information about what trials you might be eligible for.

Do I have to join a trial?

Being a part of trial is a personal decision. It can be overwhelming to learn about them all, but ultimately it’s up to you as the patient.

“Your care team can offer you information about whether you are eligible for a trial so that you can make an informed decision on whether you want to join a trial,” Dr. Liu said.

If you are not in a trial, you will receive the standard treatment. By participating in a clinical trial, you may be among the first to receive a new treatment that is otherwise not available. But, the new treatment has not yet been proven to be better than the current standard. It’s important you discuss this with your care team.

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