Last week the 19th Asia-Pacific Prostate Cancer Conference (APCC) was held in Brisbane. APCC 2018 brought together clinicians, scientists, nurses, allied health and general practitioners to discuss the latest issues in prostate cancer. This week's blog highlights some of the most interesting presentations from this meeting.
APCC 2018 consisted of three streams of sessions. The clinical urology stream held talks and panels by clinicians specialising in prostate cancer. Sessions included discussions on active surveillance, MRI scans, robotic-assisted prostate surgery, metastatic disease, precision medicine and PET-PSMA scans. The nursing and allied health talks featured sessions about exercise medicine, sexual health, radiotherapy, incontinence and rural nursing. The translational science sessions focussed on bone metastasis studies, hormone-targeted therapies, genetic tests and genome sequencing.
Some of the most interesting talks are summarised here:
Active surveillance - What's new? Prof Peter Carroll, University of California San Francisco.
Active surveillance is a management strategy for localised prostate cancer where treatment is delayed or avoided altogether. Men often choose active surveillance if they have a low-risk prostate cancer that may not need treatment. By delaying treatment and keeping an eye on the tumour, these men delay or avoid the nasty side effects that can result from prostate cancer treatments.
Programs for active surveillance differ between hospitals and health sectors. They usually involved regular PSA tests and biopsies. Some have additional MRIs and digital rectal exams. Prof Peter Carroll described the experiences of men on active surveillance through his health system in the US. His research has shown that active surveillance appears to be safe in well-selected patients. It is most suited to men with low Gleason grades, with favourable MRI scans, low-risk genomic markers, low PSA density scores and "low volume" disease. He has found that PSAD (PSA density reading) is a better indicator of needing treatment than standard PSA tests. MRI results (specifically PIRADS score) were also a very good indicator of upgrading to a higher-risk cancer. Men on active surveillance with PIRADS scores of 4 or 5 were more likely to have higher-risk cancers needing treatment. Prof Carroll has found that genetic tests such as OncoTypeDx, Prolaris and Decipher were also useful.
Prof Carroll reported that at his hospital in the US, 30% of men on active surveillance required treatment by 5 years after starting the program, and 50% were treated within 10 years. He considers active surveillance to be a safe option for younger men, based on research showing no significant association between younger age and time to treatment or recurrence of prostate cancer for men on active surveillance. Similar studies have also indicated that African American men are no greater risk than others when choosing active surveillance.
Testing protocols in active surveillance, A/Prof Stacey Loeb, New York 
University Langone Medical Center and the Manhattan Veterans Affairs Hospital.
PSA testing for prostate cancer sometimes picks up cancers with a very low chance of causing harm. Treatment of these cancers often results in debilitating side effects - from a treatment that has a very low chance of saving lives. A/Prof Stacey Loeb spoke about the importance of active surveillance in preventing the over-treatment of prostate cancer. She described the increased use of active surveillance for low-risk prostate cancer as reducing the harms from screening programs.
There remains confusion about the recommendations of tests for men on active surveillance. Different hospitals have very different protocols for the number of PSA tests, biopsies and scans recommended each year. Official guidelines differ considerably between and within different countries. A/Prof Loeb's research has shown that men from the US do not all follow their own hospital's program. Only 59% of US men on active surveillance had the recommended blood tests over 10 years on the program. Only 34% of these men had 2 or more biopsies over 5 years on the program.
Unfortunately, biopsies for prostate cancer have some risk associated with them. A/Prof Loeb was part of a taskforce that recommended ways to reduce these risks. They recommended careful patient selection, assessment of risk factors, counselling of risks to the patient and the use of transperineal biopsies where necessary to reduce risk. Her recent research comparing active surveillance to watchful waiting has shown that active surveillance extends life more than watchful waiting. This was particularly so for men with higher-risk disease features. But this was partly offset by the decrease in quality of life.
High vitamin D levels are associated with improved overall survival of men with aggressive prostate cancer. Dr Visalini Nair-Shalliker, Cancer Council NSW.
Dr Visalini Nair-Shalliker spoke about her study assessing the association of vitamin D levels and prostate cancer survival. Her talk focussed on a cohort study. This study design involved recruiting men with prostate cancer to the study and tracking their progress over time. Recruitment started over 10 years ago. Over 2000 men from NSW and Queensland joined the study. At the start of the study, the participants were interviewed about their lifestyle factors. Blood samples were taken and levels of vitamin D were measured. These men with prostate cancer were followed-up in the future and death records were assessed, if necessary.
Results of this study showed that men who had lower levels of vitamin D were more likely to die. This is not surprising. Vitamins are essential for good health, therefore men with low vitamin levels are likely to have worse health. The chance of dying from prostate cancer, however, was the same, regardless of vitamin D levels. But this study also showed that men with lower vitamin D were more likely to have aggressive prostate cancer (intermediate to high-risk of spreading by metastasis). As this was an observational study, the results were not sufficient to show that the low vitamin D was a cause of higher-risk prostate cancer. But Dr Nair-Shalliker concluded that:
"Maintaining high circulating Vitamin D levels after treatment may increase overall survival after a prostate cancer diagnosis, particularly in those with more aggressive disease".
Dr Nair-Shalliker is now running a randomised controlled trial to test the possibility that vitamin D supplements can help prevent disease progression. The ProsD trial is currently recruiting men on active surveillance to test the benefits of nutritional support in preventing prostate cancer progression.
Urinary continence physiotherapy following prostate cancer treatment, Dr Ryan Stafford (University of Queensland).
Although we know that physiotherapy can benefit men recovering from urinary incontinence, the best management programs for men directly after their prostate surgery are controversial. Despite many studies of various designs, the evidence remains conflicting as to what type of intervention has the best results. Earlier trials used exercises that we know now are not optimal for controlling men's urinary continence.
Dr Stafford's research has used transperineal ultrasound to ask which muscles are important for male urinary control. His research has compared the pelvic floor muscles in men who are and are not continent after prostate surgery. He was able to calculate the distance the muscles move during contraction using ultrasound. This can help to estimate how well the exercises are working. Dr Stafford's research has helped define the muscles needed for good urinary continence in men and the types of exercises that help strengthen them. He has shown that the urinary sphincter is the most important muscle that needs to be strengthened in men after prostate surgery.
Dr Stafford, with Prof Paul Hodges, will soon start an Australian randomised controlled trial to test a physiotherapy program that aims to improve urinary continence after prostate surgery. This trial will recruit men aged between 30 and 70 who are scheduled to undergo prostate surgery. The trial will test two different physiotherapy programs to improve pelvic floor strength, compared to usual care. Participants will be followed-up for 12 months. Urethral muscle training will involve an individualised program of pelvic floor muscle training that relies on the principles of motor skill training of the muscles that control urethral pressure, with ultrasound imaging used for assessment.
Risk factors for prostate cancer, A/Prof David Smith, Cancer Council NSW.
A/Prof David Smith spoke about the difficulties in interpreting risk factor studies. A risk factor is a characteristic of a person that is associated with a higher risk of getting a disease, such as prostate cancer. The risk factor may not be a direct cause, but rather an indication that they have a higher than usual probability of getting the disease. A protective factor is similar, but associated with a decreased risk of getting the disease. Risk factors can be modifiable (e.g. smoking), but can also be non-modifiable factors, such as aging.
Some knownrisk factors for prostate cancer include older age, family history of disease, poor diet and ethnicity. We know that some ethnicities, such as African Americans, have a higher risk of being diagnosed with prostate cancer.
There are countless articles in the media describing potential risk factors and protective factors for prostate cancer. A recent example is an article describing a risk factor - stating that eating dinner late at night can increase the risks of prostate cancer. These news articles are often conflicting and can be misleading. It is difficult for patients, doctors and even scientists to interpret which of these proposed risk factors should be used to guide our behaviour.
A media story published last month described height as a risk factor for aggressive prostate cancer. It was based on an article published in a journal called Cancer Epidemiology, Biomarkers & Prevention. The study examined a group of 1,357 men with prostate cancer and 7,990 men without prostate cancer. They were similar in age and used the same GPs. This study showed that the men with high-grade prostate cancer were more likely to be taller than the men without the cancer. But the were no differences in heights between men with low-grade prostate cancer and their healthy counterparts. The study authors stated that their results "indicate a limited role for childhood environmental exposures" in high-grade prostate cancer. The article also included a meta-analysis of 58 different studies testing the association of height and prostate cancer. This analysis showed that for every 10cm increase in height there was a 6% increase in risk of prostate cancer.
A/Prof Smith used this article as an example to demonstrate the issues around interpretation of risk factor information. He considered this to be a good study, particularly because it showed increasing effects on risk with increasing height. This study design is called case-control. As it's not a randomised controlled trial, the results cannot be used to direct infer causation. Rather, these studies "help establish causality". Height itself is unlikely to be causing the increased risk of prostate cancer. Rather, it may be that taller people have other characteristics that are causing an increased risk. These could be childhood environmental exposures or hormone levels, or other characteristic of taller people, that are influencing prostate cancer risk.
One way to assess this study's relevance for Australia men is to compare it to similar studies involving Australians. The 45 and Up study is a very large Australian trial of aging people. Over 267,000 people were recruited to this study between 2006 and 2008. 4,315 men in 45 and Up were diagnosed with prostate cancer after recruitment. After adjusting for differences in age, PSA-testing history and other factors, the 45 and Up study showed a significant association of height and high-grade prostate cancer, but not low-grade disease.
A/Prof Smith discussed the possible reasons why this association might exist. Although taller people had a greater risk, this does not mean that height, or factors that lead to greater height, are the causing this increased risk.
45 and Up is a multi-cultural study involving many ethnic groups. The tallest men in the study originated from Australia, New Zealand and Europe. The shorter men in the study originated from Asian countries. The men from Australia, New Zealand and Europe were more likely to have regular PSA tests than those from Asia. We know that the more you test for prostate cancer with PSA blood tests, the more you find it. So different PSA-testing levels between the taller and shorter men may be the reason for a greater risk of being diagnosed, rather than the differences in height between the two groups of people.
A/Prof Smith concluded that we need to be cautious about observational studies as the causes of the associations that these studies find are not always clear. His message for men who are concerned about risk factors for prostate cancer is to talk to their doctors about whether regular PSA testing is a good idea for them.
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