Sunnybrook Magazine Sunnybrook Magazine - Spring 2020

Researchers are investigating an innovative new approach to prostate cancer detection

Sunnybrook scientist Hon Leong developed a liquid biopsy approach in the hopes of preventing aggressive over-treatment of prostate cancer. (Photography by Kevin Van Paassen)

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.

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.”

How it works

Illustration by Emblem

Click to view plain text version of infographic

Measuring the presence of cancer in the blood

The PolySia liquid biopsy enables doctors to measure the amount of prostate cancer cell fragments in a patient’s blood. If there are high levels of these fragments in the blood, the patient likely has a high-risk tumour. If there are low levels, the patient likely has a low-risk tumour. The illustration below shows what doctors are looking for in a liquid biopsy:

  1. A prostate cancer cell (indicated in green) is about to release a cell fragment into the bloodstream (indicated in red)
  2. Within seconds, the cell fragment has been fully released into the bloodstream

The two-step test that will help diagnose prostate cancer in a non-invasive way is in development right now at Sunnybrook. Within several years, men who come in for prostate cancer testing may have the answers they’re looking for right away – and with fewer risks associated with an invasive needle prostate biopsy.

Step 1:

A blood test, called a liquid biopsy, screens the blood for “cancer cell garbage,” explains Hon Leong, PhD, a scientist with the Sunnybrook Research Institute. The test identifies PolySialic Acid found on this “cellular garbage,” which is discarded by prostate cancer cells. If the cancer cells aren’t there, the acid on this “garbage” won’t show up in blood work. Scientists analyze how many of these pieces of “garbage” have this acid in the blood, and get information about whether the cancer risk is low-grade or high-grade.

Step 2:

The individual will get an MRI of the prostate that can identify any abnormalities or areas that may harbour cancer. If the imaging result looks like there might be something there, the blood test result (Step 1) will make the final decision if it is low- or high-risk cancer. Sunnybrook researchers are currently working at enhancing MRI using artificial intelligence to assist them in pinpointing the subtlest of changes invisible to the naked eye.

The patient benefit:

The two-step approach means more information, less anxiety and results within days rather than weeks. Earlier results will also pave the way for faster treatment. And unlike the PSA test, which has an accuracy rate of detecting cancer of between 55 per cent and 60 per cent, the liquid biopsy will be at least 95 per cent accurate, says Leong, when coupled with advanced MRI screening.

About the author

Anna Sharratt