What is the best treatment for high-risk prostate cancer?

Introduction

High-risk prostate cancer is that which is likely to spread outside of the prostate and is life-threatening if left untreated. This risk is defined based on three criteria: the PSA (blood test) level, the stage of the cancer (i.e. how bad it feels on prostate exam or looks on a scan), and the Gleason score (i.e. how aggressive the cancer areas look when seen under a microscope). Anyone with a PSA>20, stage of T2c or above, or a Gleason score of at least 8 is considered to have high-risk prostate cancer.

Most men who present with prostate cancer in the UK that is confined to the prostate do NOT have high-risk prostate cancer. However, the numbers that do are increasing. Why? Because in an attempt to decrease picking up low-risk prostate cancer there are doctors that are testing for prostate cancer less often than they used to. This has reduced the numbers of men who are being diagnosed with low-risk disease, but unfortunately has increased the numbers presenting with the more dangerous, high-risk cancer.

While most UK surgeries for prostate cancer are done for men with low or moderate risk prostate cancer, this trend varies among different regions of the country and different surgeons. This is because of screening patterns that vary among different areas of the country and because surgery for high-risk prostate cancer is more challenging, and hence many surgeons shy away from it. Let me explain why.

It’s a bit like learning to play a sport; let’s take golf as an example. When you start, you play on 9-hole Par 27 courses and wait until your skills are good enough to tackle the more challenging 18-hole Par 70+ courses. To graduate to these more difficult golf courses, you have to practise, and generally the more you practise the better you get. If you play once a week, you do worse than if you play 3 times a week. Similarly, the average UK surgeon performs robotic prostatectomy once a week or less, and thus is less able to do the high-risk surgeries than those surgeons that operate 3 times per week like all the Santis surgeons.

Treatment

There is good evidence from large studies in the UK and abroad that radiotherapy given with hormone treatments work well for high-risk prostate cancer. But the question is, how does surgery compare to radiotherapy for high-risk prostate cancer? I published one of the best papers in this field in the British Medical Journal; it has had over 30,000 views and can be found here along with a 4-min video clip summarising the research: http://www.bmj.com/content/348/bmj.g1502

 

 

This paper, and others, showed that surgery for high-risk prostate cancer, especially in young, fit men who were unlikely to die of other causes, might result in better survival than radiotherapy. This has led to 60% of all European surgeons now favouring surgery over radiotherapy for high-risk prostate cancer; Surcel et al. Eur Urol 2014: https://www.ncbi.nlm.nih.gov/pubmed/24802335

However, it might be more complex than a simple head-to-head between surgery and radiotherapy. There is anecdotal evidence that surgery PLUS radiotherapy might be the best treatment. This is based on the theory that surgery is the best treatment for the prostate itself, but radiotherapy has a wider treatment range such that escaped cells outside the prostate are better treated with it than the more anatomically precise surgery. Hence, for high-risk prostate cancer which have a high likelihood of harbouring cancer cells outside the prostate, giving surgery to the prostate PLUS radiation to mop up any straggler cancer cells might work best. We at Santis are among the global leaders in this field, and are setting up studies to examine whether the combination of surgery with radiotherapy works best in high-risk prostate cancer.

Metastatic prostate cancer

Metastatic prostate cancer is yet more serious than high-risk prostate cancer. Here, the risk has been realised, and the cancer has now already spread to other areas, most often the bones. When the cancer has spread to lots of bones or other organs, it is poly-metastatic prostate cancer; when it has only spread to 3 or fewer bones it is oligo-metastatic prostate cancer. This distinction is a fairly new thing that the author has helped disseminate across the world. The reason for it is that there is emerging evidence that oligo-metastatic prostate cancer is potentially curable, or at least, can be held at bay for many years with treatment given to the prostate itself.

For poly-metastatic prostate cancer, treatment options will include hormonal therapies, chemotherapy, abiraterone, enzalutamide, and other drugs. However, for oligo-metastatic prostate cancer, as well as these drug treatments, it appears that the prostate gland itself acts as the mothership and gives off certain chemicals that drive the secondary deposits in the bone to progress and become poly-metastatic. When poly-metastatic, the bone cancers drive each other and get away from the control of the mothership (prostate). Hence, by intervening when the bone disease is still under control of the prostate itself, we might be able to stop the secondaries in the bones from progressing further. A large study on thousands of men in Sweden seems to suggest this, which I published earlier this year:
https://www.ncbi.nlm.nih.gov/pubmed/28416350

That’s the theory at least, and we at Santis are investigating this in a proper clinical trial funded by the Prostate Cancer Foundation (www.pcf.org) and The Urology Foundation (www.theurologyfoundation.org). You can read more at the Cancer Research UK website.

We are actively seeking participants for this trial so please reach out to us if you have oligo-metastatic prostate cancer (1-3 areas of bone secondaries from prostate cancer) and are interested in discussing this option. Santis is the ONLY group in which all surgeons are actively involved in this study and any of us would be delighted to see you.

After treatment

For those undergoing surgery for high-risk and oligo-metastatic prostate cancer, the outcomes might be worse on average than for men with lower risk prostate cancer. However, the outcomes are still excellent for most men, especially in the hands of the world-leading surgeons, as seen in this paper I published last year in the world’s best Urology journal: https://www.ncbi.nlm.nih.gov/pubmed/26038098

The key thing to remember though is that the outcomes are surgeon-dependent, and how well you do across the important yardsticks of prostate cancer surgery (getting a negative surgical margin, suffering no complications, getting dry quickly, lowering the risk of prostate cancer coming back after treatment), is dependent on how experienced and skilled your surgeon is.

Summary

High-risk prostate cancer is becoming more and more common, and there is increasing evidence to support operating on these men. However, this should only be done as part of the UK clinical trial for those men with disease that has spread to a few bones (oligo-metastatic prostate cancer). For both high-risk and oligo-metastatic prostate cancer, how well patients recover and their longer-term quality of life is dependent on the skills and experience of the surgeon.

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