More than 16,000 Australians will be diagnosed with melanoma each year. Most of these will be caught early, and can be cured by surgery.

However, for patients with advanced or metastatic melanoma, which has spread from the skin to other organs, the outlook was bleak until the advent of targeted therapies (that attack specific cancer traits) and immune therapies (that leverage the immune system). Over the past decade, these treatments have seen a significant climb in the number of advanced melanoma patients surviving for at least five years after diagnosis, from less than 10% in 2011 to around 50% in 2021.

While this is great news, there are still many melanoma patients who cannot be treated effectively with current therapies. Researchers have developed two exciting new therapies that are being evaluated in clinical trials for advanced melanoma patients. Both involve the use of immunotherapy at different times and in different ways.

The first results from these trials are now being shared publicly, offering insight into the future of melanoma treatment.

Immunotherapy before surgery

Immunotherapy works by boosting the power of a patient’s immune system to help kill cancer cells. One type of immunotherapy uses something called “immune checkpoint inhibitors”.

Immune cells carry “immune checkpoint” proteins, which control their activity. Cancer cells can interact with these checkpoints to turn off immune cells and hide from the immune system. Immune checkpoint inhibitors block this interaction and help keep the immune system activated to fight the cancer.

Results from an ongoing phase 3 trial using immune checkpoint inhibitors were recently published in the New England Journal of Medicine.

This trial used two types of immune checkpoint inhibitors: nivolumab, which blocks an immune checkpoint called PD-1, and ipilimumab, which blocks CTLA-4.

Some 423 patients (including many from Australia) were enrolled in the trial, and participants were randomly assigned to one of two groups.

The first group had surgery to remove their melanoma, and were then given immunotherapy (nivolumab) to help kill any remaining cancer cells. Giving a systemic (whole body) therapy such as immunotherapy after surgery is a standard way of treating melanoma. The second group received immunotherapy first (nivolumab plus ipilimumab) and then underwent surgery. This is a new approach to treating these cancers.

Based on previous observations, the researchers had predicted that giving patients immunotherapy while the whole tumour was still present would activate the tumour-fighting abilities of the patient’s immune system much better than giving it once the tumour had been removed.

Sure enough, 12 months after starting therapy, 83.7% of patients who received immunotherapy before surgery remained cancer-free, compared to 57.2% in the control group who received immunotherapy after surgery.

Based on these results, Australian of the year Georgina Long – who co-led the trial with Christian Blank from The Netherlands Cancer Institute – has suggested this method of immunotherapy before surgery should be considered a new standard of treatment for higher risk stage 3 melanoma. She also said a similar strategy should be evaluated for other cancers.

The promising results of this phase 3 trial suggest we might see this combination treatment being used in Australian hospitals within the next few years.

mRNA vaccines

Another emerging form of melanoma therapy is the post-surgery combination of a different checkpoint inhibitor (pembrolizumab, which blocks PD-1), with a messenger RNA vaccine (mRNA-4157).

While checkpoint inhibitors like pembrolizumab have been around for more than a decade, mRNA vaccines like mRNA-4157 are a newer phenomenon. You might be familiar with mRNA vaccines though, as the biotechnology companies Pfizer-BioNTech and Moderna released COVID vaccines based on mRNA technology.

mRNA-4157 works basically the same way – the mRNA is injected into the patient and produces antigens, which are small proteins that train the body’s immune system to attack a disease (in this case, cancer, and for COVID, the virus).

However, mRNA-4157 is unique – literally. It’s a type of personalised medicine, where the mRNA is created specifically to match a patient’s cancer. First, the patient’s tumour is genetically sequenced to figure out what antigens will best help the immune system to recognise their cancer. Then a patient-specific version of mRNA-4157 is created that produces those antigens.

The latest results of a three-year, phase 2 clinical trial which combined pembrolizumab and mRNA-4157 were announced this past week. Overall, 2.5 years after starting the trial, 74.8% of patients treated with immunotherapy combined with mRNA-4157 post-surgery remained cancer-free, compared to 55.6% of those treated with immunotherapy alone. These were patients who were suffering from high-risk, late-stage forms of melanoma, who generally have poor outcomes.

It’s worth noting these results have not yet been published in peer-reviewed journals. They’re available as company announcements, and were also presented at some cancer conferences in the United States.

Based on the results of this trial, the combination of pembrolizumab and the vaccine progressed to a phase 3 trial in 2023, with the first patients being enrolled in Australia. But the final results of this trial are not expected until 2029.

It is hoped this mRNA-based anti-cancer vaccine will blaze a trail for vaccines targeting other types of cancer, not just melanoma, particularly in combination with checkpoint inhibitors to help stimulate the immune system.

Despite these ongoing advances in melanoma treatment, the best way to fight cancer is still prevention which, in the case of melanoma, means protecting yourself from UV exposure wherever possible.

Sarah Diepstraten, Senior Research Officer, Blood Cells and Blood Cancer Division, WEHI (Walter and Eliza Hall Institute of Medical Research) and John (Eddie) La Marca, Senior Research Officer, Blood Cells and Blood Cancer, WEHI (Walter and Eliza Hall Institute of Medical Research)

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Most people with knee osteoarthritis can control their pain and improve their mobility without surgery, according to updated treatment guidelines from the Australian Commission on Safety and Quality in Health Care.

So what is knee osteoarthritis and what are the best ways to manage it?

More than 2 million Australians have osteoarthritis

Osteoarthritis is the most common joint disease, affecting 2.1 million Australians. It costs the economy A$4.3 billion each year.

Osteoarthritis commonly affects the knees, but can also affect the hips, spine, hands and feet. It impacts the whole joint including bone, cartilage, ligaments and muscles.

Most people with osteoarthritis have persistent pain and find it difficult to perform simple daily tasks, such as walking and climbing stairs.

Is it caused by ‘wear and tear’?

Knee osteoarthritis is most likely to affect older people, those who are overweight or obese, and those with previous knee injuries. But contrary to popular belief, knee osteoarthritis is not caused by “wear and tear”.

Research shows the degree of structural wear and tear visible in the knee joint on an X-ray does not correlate with the level of pain or disability a person experiences. Some people have a low degree of structural wear and tear and very bad symptoms, while others have a high degree of structural wear and tear and minimal symptoms. So X-rays are not required to diagnose knee osteoarthritis or guide treatment decisions.

Telling people they have wear and tear can make them worried about their condition and afraid of damaging their joint. It can also encourage them to try invasive and potentially unnecessary treatments such as surgery. We have shown this in people with osteoarthritis, and other common pain conditions such as back and shoulder pain.

This has led to a global call for a change in the way we think and communicate about osteoarthritis.

What’s the best way to manage osteoarthritis?

Non-surgical treatments work well for most people with osteoarthritis, regardless of their age or the severity of their symptoms. These include education and self-management, exercise and physical activity, weight management and nutrition, and certain pain medicines.

Education is important to dispel misconceptions about knee osteoarthritis. This includes information about what osteoarthritis is, how it is diagnosed, its prognosis, and the most effective ways to self-manage symptoms.

Health professionals who use positive and reassuring language can improve people’s knowledge and beliefs about osteoarthritis and its management.

Many people believe that exercise and physical activity will cause further damage to their joint. But it’s safe and can reduce pain and disability. Exercise has fewer side effects than commonly used pain medicines such as paracetamol and anti-inflammatories and can prevent or delay the need for joint replacement surgery in the future.

Many types of exercise are effective for knee osteoarthritis, such as strength training, aerobic exercises like walking or cycling, Yoga and Tai chi. So you can do whatever type of exercise best suits you.

Increasing general physical activity is also important, such as taking more steps throughout the day and reducing sedentary time.

Weight management is important for those who are overweight or obese. Weight loss can reduce knee pain and disability, particularly when combined with exercise. Losing as little as 5–10% of your body weight can be beneficial.

Pain medicines should not replace treatments such as exercise and weight management but can be used alongside these treatments to help manage pain. Recommended medicines include paracetamol and non-steroidal anti-inflammatory drugs.

Opioids are not recommended. The risk of harm outweighs any potential benefits.

What about surgery?

People with knee osteoarthritis commonly undergo two types of surgery: knee arthroscopy and knee replacement.

Knee arthroscopy is a type of keyhole surgery used to remove or repair damaged pieces of bone or cartilage that are thought to cause pain.

However, high-quality research has shown arthroscopy is not effective. Arthroscopy should therefore not be used in the management of knee osteoarthritis.

Joint replacement involves replacing the joint surfaces with artificial parts. In 2021–22, 53,500 Australians had a knee replacement for their osteoarthritis.

Joint replacement is often seen as being inevitable and “necessary”. But most people can effectively manage their symptoms through exercise, physical activity and weight management.

The new guidelines (known as “care standard”) recommend joint replacement surgery only be considered for those with severe symptoms who have already tried non-surgical treatments.

I have knee osteoarthritis. What should I do?

The care standard links to free evidence-based resources to support people with osteoarthritis. These include:

• education, such as a decision aid and four-week online course
• self-directed online exercise and yoga programs
• weight management support
• pain management strategies, such as MyJointPain and painTRAINER.

If you have osteoarthritis, you can use the care standard to inform discussions with your health-care provider, and to make informed decisions about your care.

Belinda Lawford, Postdoctoral research fellow in physiotherapy, The University of Melbourne; Giovanni E. Ferreira, NHMRC Emerging Leader Research Fellow, Institute of Musculoskeletal Health, University of Sydney; Joshua Zadro, NHMRC Emerging Leader Research Fellow, Sydney Musculoskeletal Health, University of Sydney, and Rana Hinman, Professor in Physiotherapy, The University of Melbourne

This article is republished from The Conversation under a Creative Commons license. Read the original article.