Building better predictions for prostate cancer patients
Professor William Watson and colleagues in the Prostate Cancer Research Consortium have shown how drawing on multiple sources of information could improve prostate cancer diagnosis and treatment decisions.
One in eight men in Ireland will have a diagnosis of prostate cancer in their lifetime. After that diagnosis, the disease can develop in different ways. The tumour may be aggressive and treatment may help to slow it down or even halt it. Or, in many cases, the tumour is ‘indolent’ or non-aggressive, and if left alone it would have no impact on the man’s lifespan or quality of life.
But how can we tell whether a tumour is slow or speedy? A paper by UCD scientist Professor William (Bill) Watson and colleagues has successfully explored a new approach. By analysing the results of several types of information together, the research has shown a more accurate prediction of how aggressive a given prostate tumour is.
“In the vast majority of cases, men with a prostate tumour will die with their tumour and not from it,” explains Professor Watson, who is Professor of Cancer Biology at the UCD School of Medicine. “Also, because prostate cancer is generally an ageing man’s disease, and older men are more likely to have other conditions, you want to avoid interventions like surgery or radiation or chemotherapy unless they are really necessary.”
Currently, when a man has suspected prostate cancer, a surgeon takes a small piece of the prostate tissue so that a diagnosis can be made. “This tissue biopsy can help to tell whether there is a tumour present in sample tissue, and whether the tumour is indolent or aggressive,” explains Professor Watson. “But there can be a sampling error – there may be a tumour elsewhere in the prostate that hasn’t been sampled, or that sample may not be representative of other parts of the tumour. So you don’t always get a clear picture of whether you are dealing with an indolent or aggressive disease.”
Professor Watson and colleagues are developing a more comprehensive approach to learning about the cancer in an individual. They are drawing on several types of information about the tumour, including changes to DNA, which genes are being switched on, levels of particular proteins and the nature of the sugars attached to these proteins in tissue and in blood.
“We set out to test the hypothesis that by combining these multiple sources of data from a patient, you would get a better prediction about the status of the tumour,” he says.
The study was made possible by patients in Ireland donating removed prostate tissue and blood samples to the Prostate Cancer Research Consortium (PCRC) Bioresource, which is supported by the Wellcome Trust-Health Research Board (HRB) Dublin Centre for Clinical Research and the Irish Cancer Society.
“One of the things that makes the PCRC Bioresource stand out by international standards is that we have this comprehensive collection of paired blood and tissue samples from almost 1,000 men, and we have followed up with the patients to see whether and how the disease progressed clinically,” says Professor Watson, who is lead Principal Investigator of the PCRC. “And because we have been building up this resource for more than a decade, it means we can now carry out these kinds of studies, which would not otherwise be possible.”
Members of the PCRC were able to analyse biochemical features of tissue and blood samples and outcomes in more than 150 individuals. In a paper published in the journal Molecular Oncology, the researchers describe how their process of drawing on multiple types of information from the blood and tissue samples at the time of diagnosis allowed much more accurate predictions about the status of the cancer – whether it was indolent or aggressive.
“When we looked at the clinical variables, the ones that are typically used now, we saw the prediction result was about 72% accurate, and when we integrated all the information, the result was about 94% accurate,” says Professor Watson. “So we can see that our integrated approach was highly predictive.”
The researchers are now seeking funding to validate the approach in larger groups of patients, and the ideal impact would be to more accurately match the correct treatment approach to the patient at the time of diagnosis. “If someone has been diagnosed and we predict he has an aggressive cancer then we know he could benefit from treatment,” says Professor Watson. “Or if we predict he has indolent cancer, then he can avoid surgery and radiation and all the side effects that go with them.”
…if we predict he has indolent cancer, then he can avoid surgery and radiation and all the side effects that go with them.
“Another major benefit of the integrated approach is being able to learn more from blood samples”, he adds. “Our current work is determining if any of the blood markers could be used to monitor patients with indolent cancer and who are on active surveillance sparing them the need for repeated tissue biopsies.”
The research continues to rely on patient information and samples to move forward, but implementing the recent health data regulations in Ireland will introduce new challenges in the future use of this information.
“It’s a question of resources,” says Professor Watson. “Where we will comply with the new data regulation, the more resources we put into this there are less available for the research, and when we talk to patient representatives and advocacy groups about this, they say patients have already given consent and just want the research done.”
What drives Professor Watson to keep going with the research is a desire to improve the decisions that in turn improve patient outcomes. “I am lucky that I work closely with clinicians on clinically relevant questions which will impact on patients,” he says. “Translating the extensive scientific advances drives my interest in this space.”
He is also motivated to train the scientists of the future who will further grow this translational work. “I co-ordinate the Biomedical Health and Life Sciences BSc honours degree in UCD, and we are training the next generation of translational scientists at the interface of science and medicine in how to progress scientific ideas into clinical utility,” he says. “We also ensure that the students learn about patient engagement. This is such a big change from when I was doing my training where scientists tended to work in isolation. Now we get to engage with patients and understand their needs, and they help to inform the research we do.”
Professor William Watson was in conversation with Dr Claire O’Connell (BSc, (Hons) 1992, PhD 1998), journalist with The Irish Times and Silicon Republic and Irish Science Writer of the Year 2016.
We also ensure that the students learn about patient engagement. This is such a big change from when I was doing my training where scientists tended to work in isolation. Now we get to engage with patients and understand their needs, and they help to inform the research we do.