Tag Archives: active surveillance

ProtecT and survival: what do we make of major prostate cancer trial?

Simon Crompton

Simon Crompton

It’s a study worthy of headlines, and it got them. The early results of the ProtecT trial have been published – and they’re important if only because this is the first randomised study comparing three common approaches to localised prostate cancer: surgery, radiotherapy and active surveillance.

The news stories have been clear on the main finding of the trial: “Monitoring of prostate cancer as effective as treatment”; “Prostate cancer patients live just as long with no treatment, experts have revealed”. The stories followed the upbeat lead of press releases from the researchers’ own institutions, the universities of Bristol and Oxford: “Active monitoring is as effective as surgery and radiotherapy, in terms of survival at 10 years, reports the largest study of its kind,” they said.

The researchers found that around 1% of the 1,643 men with localised prostate cancer had died after ten years, regardless of whether they had undergone a prostatectomy, radiotherapy or a programme of regular testing to check for progression (active surveillance). And those on active surveillance had the added benefit of avoiding the severe side effects that can result from treatment. Positive about the benefits of monitoring over intervention, then.

Increased risk of metastasis

But if you’d read the editorial in the New England Journal of Medicine accompanying the study’s publication, you might believe you were reading about entirely different research. This focused on the finding that, although similar numbers in each group survived at ten years, those in the active surveillance group were more than twice as likely to have metastases and disease progression.

To the editorial author, radiation oncologist Anthony V D’Amico, an increased risk of metastasis in active surveillance was the most significant conclusion to be drawn from the research.

“Therefore, if a man wishes  to avoid metastatic prostate cancer and the side effects of its treatment,” he wrote, “monitoring should be considered only if he has life-shortening coexisting disease such that his life expectancy is less than the 10-year median follow-up of the current study.”

No definitive conclusions

The fact is that, though important, these results are still too limited for anyone to be able to draw definitive conclusions about the merits of active surveillance. If anything, they seem to have further polarised the stances of those set on opposite sides in the prostate cancer overtreatment debate.

So next, to move on, we need to see what happens beyond 10 years in terms of mortality. And we need a more stratified breakdown of what happened to men with different Gleason scores (indicators of cancer aggression). The men included in the active surveillance group in this study had higher Gleason scores than would normally be eligible for active surveillance – so the overall results may not reflect this approach accurately.

The headlines, of course, never reveal the full story.

The real definition of active surveillance: what it means for a patient

Simon Crompton

Simon Crompton

It was only on the second day of ESO’s conference on active surveillance of low risk prostate cancer this weekend that the question was raised: what actually is active surveillance?

“Watchful waiting” and “active surveillance” were for many years regarded as the same thing. In fact, that Bible of medical veracity Wikipedia still equates the two – as observational approaches that allow men with low risk prostate cancer the opportunity to avoid or delay aggressive tests and treatments.

But the field has changed and specialised rapidly in the past 20 years, with the European School of Oncology taking a lead on extending knowledge in the field – organising three expert conferences, of which this was the latest. Those urologists, radiologists and public health experts attending such events are very clear that active surveillance is different from watchful waiting.

What’s the difference?

As Axel Semjonow from the University Hospital Muenster, Germany, explained: watchful waiting delays the need for palliative treatment, while active surveillance delays the need for curative treatment. Active surveillance is more likely to involve a schedule of assessment and tests, such as biopsy. Watchful waiting is more likely to apply to men with a life expectancy of less than ten years and will often follow active surveillance.

But these definitions only became widely used in 2008.

The rapid acceptance that active surveillance is an important strategy for treating low risk prostate cancer has had a lot to do with growing concerns about overdiagnosis and overtreatment in prostate cancer. For many men, biopsies, prostatectomy and radiotherapy produce effects far worse than their cancer ever would. A recent study showed that just 1% of men whose low risk prostate cancer is managed through active surveillance go on to die of the disease.

Conferences such as this are incredibly important for determining the best ways of selecting patients for active surveillance and of monitoring them while on the programme.

But active surveillance is still an emerging art, under-researched and ill-defined. The role of MRI scanning, for example, was a continual source of debate during the conference. We know a lot about its ability to diagnose prostate cancer. But in terms of its accuracy at monitoring disease progression, there are few yardsticks.

When cure seems the only goal

And, beyond the realms of such meetings, the very meaning of active surveillance is poorly understood. There are still varied definitions in scientific papers and guidelines. For prostate cancer patients, mere scientific statements of meaning do little good. Active surveillance offers many men the chance of a long and good quality of life without treatment side effects, but that might be hard to understand amid the stress of diagnosis when “cure” seems the only goal.

As several participants at the conference pointed out, amid the excitement of scientifically advancing this important field, the difficulty of patients understanding the approach and their personal risk should not be forgotten. Good communication has to be at the heart of programmes – and making sure that everyone understands what active surveillance really means today would be a good start.

Highlights from the conference:

 

We have breast cancer units – so why not prostate cancer units?

Simon Crompton

Simon Crompton

There are few certainties in prostate cancer: intense debate continues to surround the benefits and drawbacks of screening, the relative merits of surgery, brachytherapy and radiotherapy and surgery, the right times for active surveillance and radical therapies. But through all the dialogue, a plain fact is now being acknowledged that casts a light on all aspects of diagnosis, treatment and continuing support. The patient’s own preferences, personality and circumstances have a central bearing on what the “right” decisions actually are.

Thanks to the efforts of patient organisations such as Europa Donna, this principle has already received widespread recognition in the most common cancer in women, breast cancer. A new European Parliament policy in 2003 prompted the growth of specialist breast units based around patient-centred multidisciplinary care teams. This, it has become clear, is the best way to take account of a wide range of individual needs and preferences.

The most common cancer in men, prostate cancer, is not yet widely benefitting from such a re-alignment. But that may change.

ESO promotes the specialist model

The specialist unit model is particularly well suited to prostate cancer and its convoluted decision-making. Not only does it provide specialist care and support at every stage – whether it be active surveillance, surgery and radiotherapy side effects or palliative care. It can also help patients recognise emotional needs that might not otherwise be addressed – and studies show that men are less likely than women to recognise the need for help.

These are all points that have been made with some force by the European School of Oncology’s Prostate Cancer Programme, led by Riccardo Valdagni, Scientific Director of the Division of Radiotherapy 1 and the Prostate Cancer Programme at the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. The programme developed the concept of prostate cancer units (PCUs), and in an influential article in the European Journal of Cancer in 2011 set out the concept and what was involved in terms of professional education and experience. The central principle is specialist care, multi professional care.

The idea is catching on. When I recently interviewed Per Anders Abrahamsson from the European Association of Urology, he said he supported PCUs, adding that non-prostate specialists had been treating the condition for too long. “We are definitely behind the concept of units. In many countries already, for example the UK, you now have to operate a certain number of cases a year and demonstrate follow-up and outcome to be allowed to carry out a procedure. I am convinced this is what will happen in all European countries.”

New paper sets the way forward

In August, the case for Europe-wide PCUs moves a step onwards with the publication of a new position paper from ESO in Critical Reviews in Oncology/Hematology, setting out the core criteria for defining the units in European countries. The criteria have been compiled by the PCU Initiative in Europe Task Force, established by ESO in 2012 to set standards for quality comprehensive prostate cancer care and designating care pathways in PCUs.

As Riccardo Valdagni says in the paper, there is a general cultural shift towards multiprofessional working which should win a consensus among the uro-oncologic community. But the influence of those who stand to benefit most could be crucial.

“The efforts of patient advocacy groups in increasing patients’ awareness about the importance of being treated and followed up in top quality centers are key elements for the success of the initiative,” he writes.

 

 

 

 

 

 

More pieces in the prostate puzzle

Simon Crompton

Simon Crompton

When are the costs of surgery too great? It’s long been a burning question in prostate cancer, and papers presented over the past few days at the European Association of Urology’s conference in Madrid have added a few more pieces to the risk versus benefits jigsaw.

Speaking recently to Per-Anders Abrahamsson, the association’s Secretary General, for an article to be published in Cancer World, I was told about the current gaping holes in research in prostate cancer. For example, there is no randomised trial comparing radiation therapy with surgery – which constantly gets in the way of good clinical decision-making.

Clinicians and patients are also short of information to weigh about the long-term side effects of treatments – and research presented at EAU showed that the evidence that clinicians currently act on might also be misleading. Take the incidence of erectile dysfunction following prostate removal surgery. The standard way of measuring erectile dysfunction is by the International Index of Erectile Function (IIEF), but researchers from the Herlev Hospital in Copenhagen realised that this might not take into account the sudden change in erectile dysfunction brought about by prostate surgery.

So they added another simple question to the survey: “Is your erectile function as good as before the surgery? (yes/no)”

The difference it made to responses from prostate surgery patients was striking. Responding to the IIEF survey without the additional question, nearly 24% of patients registered no decline in their erectile function after surgery. But when they were asked the additional question, just 7% said their erections were as good as before surgery.

That’s quite a difference for quite a lot of people. Such evidence could have a major influence on decisions about whether or not to have a radical prostatectomy.

Also presented at the conference was evidence about another kind of cost associated with prostate surgery: urinary incontinence. A team of doctors from the University of Nijmegen, the Netherlands, have used health insurance data to reveal the extent of post-operative incontinence and the costs of dealing with it. On a purely financial basis, the information is interesting enough: the average cost of incontinence pads is €210 each year (another study calculated that the 20 year additional cost of incontinence for a man after prostate surgery is close to €50,000).

But more important were the findings about the percentage of men suffering urinary incontinence in the first year after a urology procedure or follow-up. For men undergoing watchful waiting/active surveillance, it was 8%. For those undergoing prostate removal it was 80%, persisting into a second year for 40%.

Patient information about prostate surgery rarely specifies such figures, often offering vague reassurance that “most men” see a quick improvement in continence after surgery – as if it would be wrong to frighten them too much. As more evidence becomes available to fill in the picture on complex decisions, it’s only right that it should be shared with those it affects most.