Why do men drop out of active surveillance?

[Wendy_Winnall]

Active surveillance is a common management for low-risk, localised prostate cancer in Australia. The aim is to avoid or delay treatment until it becomes necessary. Unfortunately, guidelines vary greatly for who should go on active surveillance and what tests they should have. The Movember Foundation’s GAP3 program aims to create a global consensus on selection and monitoring of men with low-risk prostate cancer. As part of this project, the GAP3 research team have recently published a study examining the reasons why men drop out of active surveillance.

Active surveillance for prostate cancer in Australia

Active surveillance for low-risk prostate cancer is popular in Australia. Data from Victoria show that approximately 75% of men are now choosing active surveillance or watchful waiting for their low-risk prostate cancer. This has risen from 52% in 2011. The aim of active surveillance is to delay treatment for slow-growing tumours until the cancer shows signs of progressing, if it does. This helps to avoid overtreatment of harmless prostate tumours. It also delays the treatment, allowing men to live longer without the side effects from surgery or radiotherapy.

Tests used during active surveillance

Unfortunately, there is no high-level evidence from clinical trials to base guidelines for which tests to have and when to have them during active surveillance. There are numerous guidelines for active surveillance, but they all differ. Most recommend a combination of PSA tests and biopsies, with some also promoting digital rectal exams and imaging tests such as MRI. The PCFA/Cancer Council Australia guidelines recommend PSA tests every 3 months, and a physical check-up with digital rectal exams every 6 months. They recommend a biopsy to recheck the initial diagnosis at 6 to 12 months, then repeat biopsies every 2 to 3 years. Multiparametric MRIs is also recommended, if possible. However, different schedules for tests are used across different clinics and hospital in Australia.

Who uses active surveillance?

There is also a lack of agreement as to which men active surveillance is best suited. Most guidelines do agree that active surveillance is suitable for men with low-risk, localised prostate cancer. These are stage T1 or T2, with PSA at 10 ng/ml or less, a maximum of 2 biopsy cores with prostate cancer and Gleason score of 6 or 7 (3+4). But there is variety in those included in the program. One reason for this variety is the choice of the men themselves. Regardless of doctor’s wishes, men choose how to manage their prostate cancer for various different reasons.

A number of studies have shown that many men drop out of the active surveillance program. But the estimates of how many and why, vary widely from study to study. Depending on the study, the estimated drop-out rate is between 1.6% to 38%. It’s possible that the different systems in different countries and different hospitals contribute to this variety of estimates. In order to establish global guidelines for active surveillance, we need to gain a global understanding of the experiences of men on active surveillance.

Movember Foundation GAP programs

The Movember Foundation is an international leading charity for men’s health. They have been funding research and other initiatives for prostate cancer since 2004. Movember Foundation’s ultimate aim is to halve the number of men dying from prostate cancer by 2030.

Movember Foundation’s Global Action Plan (GAP) is a world-wide collaboration of research teams that aims to address five big issues in men’s health. These are:

1. Biomarkers - How can you predict the aggressiveness of prostate cancer?
2. Imaging - How can you attack cancer if you cannot see it properly?
3. Active surveillance - Once a man has been diagnosed with prostate cancer, what options does he have? The objective of GAP3 is to understand which men are the best candidates for active surveillance and which should receive treatment.
4. Exercise and metabolic health - Could exercise play a significant role in improving the quality of lives of men with advanced prostate cancer?
5. Testicular cancer - Testicular cancer treatment has a high success rate but what happens if the cancer comes back?

GAP3 - Active surveillance

The GAP3 active surveillance project started in 2013. GAP3 is integrating patient diagnosis information, imaging and biomarker data into a global central database. GAP3 aims to develop new therapeutic guidelines leading to optimal treatment for men diagnosed with low-risk prostate cancer.

Men that are newly-diagnosed with low-risk prostate cancer are often given the possibility to choose between treatment (surgery, radiation therapy, etc) or active surveillance. By choosing active surveillance, men will avoid, or at least defer, the side-effects from treatment such as urinary, bowel and erectile problems. The aim of GAP3 is to better understand which men are the best candidates for active surveillance and which should receive treatment.

GAP3 study of reasons for discontinuing active surveillance

The latest scientific paper to be published from the GAP3 project examined the reasons for active surveillance drop-out, using a world-wide perspective. The researchers were an international team from the UK, USA, Netherlands, Australia, Finland and Singapore. Prof Mark Frydenberg from Monash University and Monash Health was the Australian member of the team.

This study used records from patients from 21 different medical centres in 14 different countries. These patient records were used to collect data on men undergoing active surveillance across many different healthcare settings. 10,296 men were included in the study. They came from the countries mentioned above, as well as Switzerland, Spain, South Korea, Canada, Sweden, France, Japan, Italy.

Over the first year of active surveillance only very low numbers of men dropped out of the program. But by 5 years, 43.6% of men have dropped out of active surveillance. Of the total:

• 27.5% dropped out due to signs of their disease progressing
• 12.8% dropped out without signs of disease progression
• 1.7% converted to watchful waiting (monitoring prostate cancer that isn’t causing symptoms, but without the intent for curative treatment)
• 1.7% died of other causes
• The remaining men (approx. 56%) remained on active surveillance

About a quarter of men had transferred from active surveillance to treatment because their cancer had progressed. But an eighth of men on active surveillance had gone on to treatment even though their cancer had not progressed. The reasons why these men were dropping out are unclear. Other studies have indicated that emotional distress and anxiety may play a role.

Data was included from 236 men on active surveillance in Australia. 70% of the Australian men remained on active surveillance by 5 years and 30% had dropped out. 26.7% of the Australians had dropped out due to their disease progressing, which is quite similar to the world-wide proportion of 27.5%.

It’s very useful to get an international understanding of experiences of men on active surveillance. Given the wide variety of approaches to active surveillance, we can’t make conclusions based on a study of one region only. Previous studies of single regions have estimated a drop-out rate of between 1.6% and 38%. This wide difference is not very helpful for developing global guidelines, as is the aim of the GAP3 project. The global perspective from this new study provides a more robust understanding of adherence and drop-out from active surveillance.

The GAP3 researchers believe that there is room for improvement in two particular areas. The proportion of men experiencing disease progression on active surveillance is quite high. Better selection of the most suitable patients and better biomarkers to help predict which men had stable, low-risk disease could help to reduce the likelihood of recommending active surveillance to men whose disease will progress. The researchers also believe that too many men are leaving active surveillance for treatment even without disease progression. Better support and education during the first few years of active surveillance is suggested as a way to reduce this from happening.

One of the aims of the GAP3 project is to provide global guidelines for the management and treatment of low-risk prostate cancer. The results from this study will help guide the development of the GAP3 guidelines for active surveillance.