Active Surveillance Gains Momentum By Dr David Malouf

Prof Mark Frydenberg

• Chairman, Department of Urology, Monash Medical Centre, Melbourne
• President, Urological Society of Australia and New Zealand (USANZ)
• Co-Chair USANZ PRIAS Steering Committee

Dr David Malouf

• Head of Department of Urology, St George Hospital, Sydney
• Past-President, Urological Society of Australia and New Zealand
• National Board Member, Prostate Cancer Foundation of Australia (PCFA)
• Co-Chair USANZ PRIAS Steering Committee

In less than 20 years, the use of Prostate Specific Antigen (PSA) for prostate cancer testing has saved many thousands of lives. With this test, many prostate cancers are detected at an earlier stage, often when they are confined to the prostate. Whilst PSA testing, and improved treatments, have led to improved cancer outcomes through early detection and intervention, the inability of PSA to distinguish between the non-aggressive tumours (the ‘kittens’) and the more aggressive tumours (the ‘tigers’) has led to the diagnosis and treatment of many prostate cancers with a low potential to cause harm. Throughout the world many men diagnosed with low risk and very low risk disease have undergone treatment for a condition which may never have caused them harm. These men have been ‘cured’ of prostate cancer, but some will be living with the complications of treatment including erectile dysfunction and urinary and bowel incontinence. This is the ‘over-treatment’ phenomenon and one of the leading criticisms of the widespread use of prostate cancer testing.

Active Surveillance (AS) refers to the management of slowly growing, non-aggressive prostate cancers with careful observation and monitoring, rather than with immediate surgery or radiotherapy. With the recognition that some prostate cancers demonstrate patterns of growth measured not over weeks and months, but over years and decades, patients and their doctors have been willing to adopt AS as their primary management. Another description of this approach is deferred primary treatment, i.e., treatment when treatment is necessary, not 5 or 10 years earlier. This way, exposure to the potential side effects of treatment can be delayed, and an increasingly large number of studies have demonstrated that AS can be implemented safely and with minimal risk to the man undergoing AS.

Active Surveillance is frequently confused with Watchful Waiting and the distinction between the two is important. Active Surveillance is not passive – it is cure if and when cure becomes necessary. Watchful Waiting is typically used in
older men with prostate cancer, many of whom have other health issues to deal with. These cancers are managed with observation, often over many years. If there is evidence that the prostate cancer is growing, hormone therapy (medications which switch off the production of testosterone) can be introduced which controls the cancer in most of these men for many years.

Whilst there are many different AS protocols around the world, the fundamentals are similar. The ideal man for AS has low volume, low grade disease. This can be assessed with PSA, digital rectal examination (DRE) and biopsy results. Magnetic Resonance Imaging (MRI) scans are increasingly being used to select those men who are suitable for AS, as well as a tool for monitoring men on AS programs. Typically the Gleason Score (a measurement of the aggressiveness of the tumour) will be 6 out of 10, though some men with small volumes of Gleason 7 disease can also be managed with AS. After initial assessment of suitability for AS, monitoring involves periodic PSA tests, DREs and repeat prostate biopsies. The biopsies are usually performed every 3 years, though the introduction of MRI may reduce the frequency of follow-up biopsies. A younger man can also be managed with AS. Whilst his greater longevity means an increased chance he will eventually need treatment, many men diagnosed with low risk prostate cancer in their 50s are keen to put off the potential urinary, bowel and erectile complications of treatment for as long as possible. Some men find that anxiety associated with deferral of definitive treatment is a challenge, though studies have confirmed USANZ urological surgeons are using internationally proven Active Surveillance protocols.

Long term studies confirm Active Surveillance to be a safe and effective strategy for many newly diagnosed men with prostate cancer that good patient education can minimise this anxiety. Regular medical review and participation in a formal AS program has also been shown to keep emotional concern and distress to manageable levels. Over time, some men will need to move from AS to definitive treatment with surgery or radiotherapy as the periodic review detects changes in the volume or grade of their tumours. Many, however, remain on AS programs over many years.

Urological surgeons of the Urological Society of Australia and New Zealand (USANZ) have been quick to embrace AS. Many now have patients who have been managed with observation for in excess of 10 years without any signs of change in their low risk tumours. Recent data from the Victorian Prostate Cancer Registry confirmed that almost half of men diagnosed with low risk prostate cancer are being managed with AS. In 2010 USANZ, with generous financial support from the Prostate Cancer Foundation of Australia (PCFA), became a member society of the international AS program called PRIAS (Prostate Cancer Research International: Active Surveillance). USANZ has also been an active participant in the Movember sponsored GAP 3 Initiative which aims to improve patient outcomes by collecting information and bringing together many different AS programs into a common virtual database.

At the recent American Urological Association (AUA) Annual Scientific Meeting in New Orleans, Australian urological surgeons heard that the use of AS to treat low and very low risk prostate cancer is finally on the increase in the United States. In one study from the prestigious Johns Hopkins Hospital, almost 1300 men have been managed with AS. With average follow-up of 5 years, almost two-thirds remain on surveillance, the remainder having converted to definitive treatment.

Whilst 49 men have died over the period of observation, only 2 of those 49 deaths have been from prostate cancer. This led to a projected prostate cancer mortality of only 0.1% at both 10 and 15 years in this group of low risk patients. These encouraging results prompted the U.S. based and internationally renowned prostate cancer expert Dr Stacy Loeb to comment “The era of Active Surveillance is here. Use of Active Surveillance is finally expanding in the U.S. In the past, fewer than 10% of men in the U.S. with low-risk prostate cancer got active surveillance. Now we hear that more than 70% of a group of men in community urology practices are getting active surveillance.”

Despite many thousands of lives saved as a result of prostate cancer testing, many in the public health arena have criticised PSA testing for doing more “harm than good”. This is a result of the known limitations of the test and the significant over-treatment which has occurred in the PSA era.

With the use of Active Surveillance for suitable patients, and high quality treatments reserved for those who need to be cured, perhaps we are entering an era where we maximise the good and minimise the harm.

Take home messages

• Not all prostate cancers are the same
• Many low volume low grade prostate cancers grow very slowly
• Active Surveillance is not the same as Watchful Waiting
• Active Surveillance means deferring the treatment of low risk prostate cancers until treatment becomes necessary
• USANZ urological surgeons are using internationally proven Active Surveillance protocols
• Long term studies confirm Active Surveillance to be a safe and effective strategy for many newly diagnosed men with prostate cancer