Great Expectations

How focal therapy could change our expectations of prostate cancer treatment

Like most surgeons, I love operating. The thrill of using your knowledge of anatomy to cut another’s skin, dissect their tissues, excise an organ and cure their cancer is intoxicating. There’s also the investment of your life that has gone into reaching the point where you can do this unsupervised. After six years of medical school plus another decade of training in the apprenticeship model, you’re the boss now. It’s a long haul, punctuated by moments of extreme intensity. Like the time I found out my final College of Surgeons fellowship exam results.

My wife Madeleine and I had three young kids at the time (now four older ones). I’d been studying after hours while working full time as a urology registrar, so my wife was essentially single parenting for more than six months. If I failed the exam, I’d have to do it all over again – we’d have to do it all over again. A bunch of Melbourne trainees had flown up to Sydney to sit the oral exams and on the final day, we were to be given our results.

There was something medieval about the process in those days. We were corralled into the university’s traditional, steep-sloping lecture theatre – like a renaissance painting of an anatomy lecture, but without the cadaver. As our names were called out one by one, we would walk down the narrow aisles to the floor of the theatre, take a sealed envelope, and promptly exit the theatre to open it. My wife was supposed to be sitting there with me for this momentous occasion, but her flight had been delayed due to thick fog at the airport. It didn’t look like she was going to make it. But straight out of a low-budget movie script, she burst into the lecture theatre just a minute before my name was called out. I took the envelope and we walked out together. Standing in the cloisters outside, I opened it and burst into tears. PASS.

So you see, there’s a lot that goes into becoming a surgeon. There’s sacrifice, especially for those around you. There is, of course, also enormous privilege. Both of which feed into the investment you make in it. Surgeons are also well-paid, and depending on the health system you work in, the more operating you do, the more money you can make. It may sound crass to raise it, but it’s a point we can’t ignore and that we’ll come back to later.

One of the operations I do is called a radical prostatectomy, which is done for prostate cancer. It means removing the entire prostate gland and rejoining the bladder to the urethra to reconstitute the urinary tract. The prostate sits deep in the male pelvis and is completely surrounded by extremely important structures – the urethral sphincter that keeps you continent of urine, the bladder, the rectum, nerves that provide erectile function to the penis and large veins that can bleed profusely if cut before being tied off. Already it’s a highly complex operation. Throw on top of that the fact that every patient’s prostate and pelvic anatomy is slightly different, and you realise the only way you can get good at it is by sheer experience (and proper training upfront, of course).

When I’d finished my surgical training, I knew how to do a radical prostatectomy, but was still very inexperienced. So I did another full year of training in it in Vancouver, Canada. Our whole family upped and moved there for a year in 2007. It proved to be a brilliant learning experience. After I started out training in open prostatectomy, Vancouver General acquired a robot just three months into my time there, so I got trained up in open and robotic techniques. I’ve been performing both for the last 17 years.

Well, what did you expect?

Just as they say that possession is nine tenths of the law, it seems that expectation must be around nine tenths of psychology. How we react to events in life results largely from the comparison against what we expect to happen. You could think of expectation as the denominator in a simple fraction, where the numerator is what actually happens, and the overall fraction is a measure of how good you feel. The higher the expectation, then, the lower the chance of feeling OK.

Why is this important here? Because when you undergo a radical prostatectomy for prostate cancer, you’re told about certain expectations. Risk calculators can tell you your chance of cure, depending on various features of your cancer. Your surgeon will tell you to expect some degree of urine leakage for the first few weeks or months after the operation, and your chance of either temporary or permanent erectile dysfunction is already significant when the erectile nerves can be spared, and even higher when they can’t be. And this is what we often see in the months and years that follow surgery for prostate cancer.

These expectations are absorbed into your mind and eventually accepted as a necessary sacrifice for being rid of your cancer. Indeed, these expectations for radical prostatectomy (and similar ones for prostate radiotherapy) have been accepted by urologists and patients alike for decades now. We expect them, so we accept them.

Our knowledge of prostate cancer and prostate anatomy has been built incrementally over the last century, leading to radical prostatectomy and radiotherapy being the standard options for treatment of localised prostate cancer, with clinical trials studying their beneficial effects. This knowledge has been accrued by specialists and researchers who are expert in this field – as it had to be.

But what if, for a moment, we ignored all this expertise and trial data, and instead took a leaf out of design thinking and at least started by empathising with the patient with prostate cancer. What do they want? We talk a lot in medicine these days about patient-centred or person-centred care. But these notions have only been tacked on or retrofitted to the long-held paternalistic institution of medicine, where the doctor knows best and the patient should keep quiet and listen to the advice. Of course, we are much better at collaborative care now, taking into account patients’ wishes and values thanks to these ideas, but we’re still arguably starting from the wrong point.

Let’s say, then, that I have a type of prostate cancer that might spread and even kill me. Of course I want to be cured, for the cancer to be eradicated completely, if possible, so I never have to think about it again. Second, I want the treatment to cause as little interruption of my normal life and function as possible. This is all pretty obvious. What sort of treatment might this look like? It might be a pill so targeted that when swallowed it destroys all prostate cancer cells in the body but leaves no side effects. Unfortunately, this doesn’t currently exist. Hopefully one day it will. Or perhaps it could be a minor procedure that only requires a short day stay in hospital, where energy is delivered safely to the prostate to destroy the cancer cells but normal prostate tissue and its surrounding structures are left intact.

Let’s now return to what expert knowledge there is about prostate cancer and the treatment options available. It just so happens that there are in fact treatments just like the minor procedure described above, and they come under the umbrella of focal therapy.

For an overview of what focal therapy for prostate cancer is, see my posts here and here.

I’ve been treating patients with focal therapy for nine years now, with our first patient treated in 2015. There are a variety of ways prostate cancer tissue can be destroyed (or ablated). You can burn it, freeze it, laser it, irradiate it, or even electrocute it. The modality we’ve used is focal brachytherapy, where we’ve taken the standard treatment option of whole-gland brachytherapy and re-purposed it, applying it only to the tumour (and a small safety margin around it), leveraging the great benefits of modern prostate imaging with MRI and PSMA PET to localise the tumour precisely. We’ve been running a clinical registry called LIBERATE to collect all our data.

Under a short general anaesthetic, the radioactive seeds are delivered via the perineal skin – exactly the same route through which the patient had their biopsy. From the patient’s perspective, it feels afterwards just like the biopsy – some soreness down below and some blood in the urine for a day or two. And that’s it. Whether there’s any erectile dysfunction down the track depends entirely on where in the prostate the cancer is. For tumours away from the erectile nerves, there’s none. For tumours near one of the two nerves, there’s about half the risk of erectile dysfunction than there is for radical treatments.

From my vantage point as a urologist who performs robotic prostatectomy regularly, I get to compare patients who are post-prostatectomy versus post-focal therapy. It is like chalk and cheese. And it is an absolute delight to see the latter. They’ve gone home the same day, they have minimal pain, they have no catheter and urine leakage, and they return to their work or normal life after two days. Contrast this to the post-prostatectomy patient who, even when performed by the minimally invasive technique of robotic surgery, are in hospital for two days, have a catheter and a bag strapped to their leg for ten days, and usually have some degree of urine leakage for the next couple of months following removal of the catheter, so having to wear pads is typical.

Focal therapy for prostate cancer, therefore, seems to fit far more easily into a schema where a solution for how to treat it originates from what the patient would want, not what a doctor might first suggest.

Of course, there are important caveats. First, focal therapy is not yet accepted as a standard treatment option. Although we have short term data showing vastly superior functional outcomes to traditional radical treatment, we still await long-term cancer outcomes. But the evidence base is building rapidly and we expect long-term outcomes to start coming through in the next five years.

Second, focal therapy is not for everyone with prostate cancer. As I’ve written previously, we know active surveillance is safe for low grade prostate cancers, and we still need radical treatment of larger, high grade cancers. Focal therapy’s place is for the group in between – patients with a single focus MRI-visible intermediate risk disease – providing a potential middle way. These intermediate-risk patients are the ones who, if they chose surveillance, would have a higher risk of cancer spreading than those with low risk cancer, and who, if they chose radical treatment, would have a high chance that their cancer would not have spread without treatment anyway. It’s exactly this cohort of patients where we’re at most risk of doing more harm than good – of overtreatment.

Focal therapy mitigates this risk by conferring far fewer side effects, which is exactly why it can not only benefit patients who receive it. It can also encourage more men to get tested with a PSA blood test in the first place, so we can aim to detect every aggressive form of prostate cancer while it’s still curable.

I love operating. But when it comes to prostate cancer, I love seeing patients after focal therapy even more. I’m hopeful that as evidence on focal therapy continues to come in, our expectations can change so that we no longer have to accept the possibility of doing more harm than good.

In future, I’ll discuss the Will Rogers effect, why modern imaging for prostate cancer makes an even stronger case for focal instead of radical therapy in intermediate risk cancer, and what the barriers to more widespread use of focal therapy might be.

Meanwhile, I’ll leave you with this 1935 quote from American novelist, Upton Sinclair:

“It is difficult to get a man* to understand something when his salary depends on his not understanding it.”

*Gendered reference as per original quote.