May 17, 2019
OICR-supported trial finds new, more sensitive imaging technique can inform treatment decisions and benefit those with recurring prostate cancer
Prostate cancer is the most common type of cancer found in men, but managing the disease is difficult because not all prostate cancers are aggressive and overtreatment can lead to unnecessary side effects, such as hormone imbalances, bowel function issues and erectile dysfunction. After initial treatment, prostate cancer patients are often monitored with a prostate specific antigen (PSA) blood test, but this test provides no information about the location and the extent of the disease. Even with traditional bone scans and CT scans, remnant traces of the disease are difficult to find and often go undetected.
A few years ago, a new, more sensitive type of imaging technique had shown promise in early clinical studies abroad and Dr. Glenn Bauman, Radiation Oncologist at the London Health Sciences Centre, wanted to bring this technique into his practice. He recognized the potential benefits of this method, but didn’t realize how much it could impact the lives of his patients.
Bringing advances to local patients
The new technique, which was originally developed at the John Hopkins Hospital in Baltimore, consisted of a chemical probe, called [18-F]-DCFPyL, which would attach only to prostate cancer cells and light up in positron emission tomography (PET) scans. It can detect very small traces of a tumour that has returned after treatment or spread to a different part of the body.
Bauman teamed up with the co-inventor of [18-F]-DCFPyL, Dr. Martin Pomper, and the Centre for Probe Development and Commercialization (CPDC) to bring this probe to patients in Ontario. CPDC implemented the stringent manufacturing processes needed to create this probe and in March of 2016, Lawson’s researchers were the first to use this technique to scan a patient at St. Joseph’s Hospital in London.
“We teamed up with experts in [18-F]-DCFPyL from the U.S. and experts in prostate PET/CT from Australia to adopt this new technique, benchmark our methods and learn from their experience,” says Bauman. “It’s with collaborations like these that we can accelerate the implementation of new methods to help patients in Ontario.”
Evaluating the benefits for those with prostate cancer
Clinical studies are needed to evaluate the effectiveness new medical techniques in practice. For this technique, Bauman and collaborators needed to test whether it’s improved accuracy and sensitivity could help make better treatment decisions.
“Treatment plans for prostate cancer differ depending on the cancer’s size and location. Whether a cancer returns in the prostate, the pelvic area or elsewhere makes a big difference,” says Bauman. “We needed to test if more sensitive imaging techniques could help patients make better treatment decisions.”
Bauman led the design and development of the Advanced Prostate Imaging of Recurrent Cancer After Radiotherapy (PICs) study to evaluate [18-F]-DCFPyL PET/CT imaging. With OICR’s support over the following two years, PICs enrolled 80 men and scanned them with both traditional imaging methods and with [18-F]-DCFPyL PET/CT.
The study group found that not only can [18-F]-DCFPyL PET/CT detect smaller traces of the disease earlier when it is more manageable, this technique changed treatment recommendations for two in every five patients.
“With this technique, we were able to clarify and reclassify a lot of the traditional scans that were previously uncertain,” says Bauman. “This means that we were able to give prostate-directed treatment with confidence for patients whose cancers reemerged in their prostate and avoid the negative side effects of systemic hormone therapy for these patients.”
Bauman says that the technique also detected double the number of cancers outside of the prostate which were too small to be detected using traditional imaging alone.
Translating clinical findings into practice
Just three years after the first [18-F]-DCFPyL PET/CT scan was taken in Canada, Bauman has embarked on the next stage in translating these findings into routine practice. He and collaborators have teamed up with Cancer Care Ontario to provide access to the [18-F]-DCFPyL PET/CT technique in Toronto, London, Hamilton, Ottawa and Thunder Bay as part of a provincial registry program.
[18-F]-DCFPyL PET/CT can be applied to other challenges that patients and clinicans face with managing prostate cancer, including monitoring how patients respond to treatments. Notably, investigators in Hamilton are investigating how these scans can help predict a patient’s response to treatment in the OICR-supported MISTR trial.
“We have been sufficiently encouraged by our results from the PICs study, through which we have demonstrated the value of this intervention and how it can benefit men with prostate cancer,” says Bauman. “I’m proud to help bring better technologies to our patients in need and enable the adoption of these technologies throughout the province.”
March 19, 2019
Collaborative research group performs the most comprehensive analysis of curable prostate cancer to date, finds key connections between different data types
As cancer researchers delve deeper into different omics studies, and technologies enable their ability to do so, it is becoming increasingly important to understand how these areas of research are interconnected. Previous studies across multiple omes – such as the genome, proteome, transcriptome or epigenome – have led to important discoveries in colorectal cancer and ovarian cancer, but prostate cancer remains largely unresolved. Researchers from the Canadian Prostate Cancer Genome Network (CPC-GENE) set out to unravel some of these mysteries.
In the most recent CPC-GENE study, published today in Cancer Cell, the research group integrated multiple levels of omics analyses to better understand the biology of intermediate-risk prostate cancer – a type of cancer in which it is notoriously difficult to predict and treat accordingly. A better understanding of this disease could lead to improved tests that can determine which tumours are aggressive and require aggressive treatment, while helping spare those whose cancer will never become aggressive the negative side effects of treatment.
“We cannot overlook the important information that we gain from looking at the bigger picture,” says Julie Livingstone, bioinformatician at OICR and co-author of the study. “In this case, this means looking at prostate cancer from multiple angles – or multiple omes – to potentially find new markers of aggressive disease.”
The study explored 76 prostate cancer tumours and found new combinations of information that could act as a better predictor of a patient’s chance of relapse than any single piece of information alone. More specifically, they identified that the combination of protein and methylation data could, on average, predict the severity of a tumour better than looking at just the proteins – the proteome – or just the methylation patterns – the methylome – alone.
“Integrating datatypes is anything but straightforward, but it illuminates interesting aspects about prostate cancer that we haven’t seen before,” says Livingstone. “In the future, we intend to pursue our multi-omic investigation and translate this understanding into better tools to inform treatment selection for men with this disease.”
Find out more about research from the CPC-GENE project on OICR News.
March 13, 2019
Researchers begin to unravel why some prostate tumours can be seen with magnetic resonance imaging and others go undetected
Determining whether a patient with prostate cancer requires aggressive therapy or active surveillance is a growing challenge for the healthcare system. Blood tests can detect early signs of prostate cancer, but these tests can lead to many unnecessary and painful biopsies for patients whose disease never becomes aggressive.
Multi-parametric magnetic resonance imaging (mpMRI), a type of non-invasive imaging technique, has the potential to help determine which patients require biopsies and which can be spared possible negative side effects, such as bleeding, pain and infection. Some tumours are visible by mpMRI while some are not, yet it’s not well understood if this visibility can predict a tumour’s aggressiveness.
Researchers at OICR have teamed up with clinicians from the University of California, Los Angeles to investigate the molecular properties of MRI-visible and MRI-invisible tumours. In their recent study, published in European Urology, they found that visible tumours have similar features to aggressive tumours and discovered new features that may be contributing to the disease’s aggression.
“Even if two tumours are similar in size and in similar positions, one still may be MRI-visible and one may be MRI-invisible,” says Kathleen Houlahan, PhD Candidate at OICR and lead author of the study. “We wanted to see if this visibility could help us determine if a cancer is aggressive, so we took the first step towards unraveling the relationship between a patient’s MRI results and the molecular characteristics of their tumour.”
Recent commentary on the study highlights Houlahan’s work as an “initial foray” into the intersection of radiology, pathology and genomics, but recognizes the limited size of her exploratory study. Recent MRI-focused clinical trials will provide larger datasets for further investigation.
“If we can better understand why some tumours show and some don’t, we could potentially use imaging to predict the course that a patient’s disease will take,” says Houlahan. “Ultimately, we hope that this technique can help reduce unnecessary prostate biopsies and ensure that the men who need treatment get the treatment they need.”
September 20, 2018
Today, OICR’s Dr. Paul Boutros was named the 2018 winner of the Bernard and Francine Dorval Prize. The award is part of the Canadian Cancer Society’s Awards for Excellence in Cancer Research.
September 13, 2018
Sunnybrook researchers develop new magnetic resonance imaging methods to help differentiate between aggressive and non-aggressive prostate cancers
Current needle biopsy techniques have limited accuracy in detecting prostate cancer and determining the tumour’s aggressiveness. New methods are needed to better detect and characterize prostate cancer so that each patient can get the treatment that is most appropriate for them.
May 17, 2018
Dr. Michael Fraser, Director of the Prostate Program in the Computational Biology group at OICR, has been named a 2018 NextGen Star by the American Association for Cancer Research (AACR). Awarded to only eight researchers around the world, AACR’s NextGen Stars program recognizes outstanding early-career scientists who have made significant contributions to cancer research.
April 19, 2018
Largest-ever study of its kind uses a tumour’s past to accurately predict its future
Toronto (April 19, 2018) – Findings from Canadian Prostate Cancer Genome Network (CPC-GENE) researchers and their collaborators, published today in Cell, show that the aggressiveness of an individual prostate cancer can be accurately assessed by looking at how that tumour has evolved. This information can be used to determine what type and how much treatment should be given to each patient, or if any is needed at all.
The researchers analyzed the whole genome sequences of 293 localized prostate cancer tumours, linked to clinical outcome data. These were then further analyzed using machine learning, a type of statistical technique, to infer the evolutionary past of a tumour and to estimate its trajectory. They found that those tumours that had evolved to have multiple types of cancer cells, or subclones, were the most aggressive. Fifty-nine per cent of tumours in the study had this genetic diversity, with 61 per cent of those leading to relapse following standard therapy.
September 25, 2017
Since mitochondria are inherited maternally, it may strike some as an odd place to go looking for connections to prostate cancer. But recently an international research team explored that relationship by looking at how the small amount of DNA contained in mitochondria, a cellular structure, is involved in prostate cancer.
August 9, 2017
Prostate cancer researchers have mapped the impact of an acquired mutation that alters epigenetic identity, the make-up of DNA, in about 50 per cent of patient tumour samples. The discovery also identifies a new opportunity for targeted therapy.
March 16, 2017
Genetic tests are being used more commonly in the diagnosis of many types of cancer. However, there currently isn’t a highly accurate test that can identify men with aggressive forms of prostate cancer, making it more difficult to choose the most appropriate course of treatment.
January 10, 2017
Prostate cancer is the most common cancer in Canadian men, but there is still no one-size-fits-all strategy for treating the disease. Currently it is difficult to choose exactly the right type and amount of treatment for each individual because it is hard to accurately assess how aggressive the cancer is. Researchers are now a step closer to bringing a powerful new prognostic tool into clinical use.
January 9, 2017
A team of researchers and clinician-scientists from across Canada have discovered a signature of 41 mutations that are common in prostate cancer and will help to prevent patients with non-aggressive disease from being overtreated. Dr. Paul Boutros, a Principal Investigator in OICR’s Informatics and Bio-computing Program and Co-Lead of the Canadian Prostate Cancer Genome Network (CPC-GENE), answered a few questions about how the signature was developed and its potential impact on patients.