Fresh thinking in the treatment of prostate cancer may give new hope to men with advanced disease.
This thinking reverses a traditional practice and is already being applied in select patients even though the evidence for it is only beginning to emerge.
The standard practice is for men newly diagnosed with metastatic prostate cancer to be put directly onto hormone therapy.
This is done in the belief that as their cancer has already spread, there is no point removing the prostate.
A surgical removal would just introduce risks and undesirable side effects, without any chance of cure.
But over the last few years this view has begun shifting.
Since the '90s, a great amount of data on surgery for prostate cancer has accumulated. When researchers began analysing it, an unexpected trend emerged.
The analysis suggested men with advanced prostate cancer who just happened to have had their prostate removed, lived longer with better quality of life, than those who did not.
Compelling advantage
Although there were confounding factors, Professor James Eastham, chief of urology at Memorial Sloan Kettering Cancer Centre in New York, says the survival advantage appeared compelling.
One analysis showed survival at five years was 23 per cent for men who had no treatment of their primary cancer, compared to 67 per cent of those who did.
He was in Canberra in February to address the Urological Society of Australia and New Zealand's 2017 conference and later spoke to The Australian Financial Review.
The new thinking is that it may be better to remove the prostate in men with advanced disease.
By advanced, he means men who have low volume metastatic disease, with perhaps three to five cancer spots in their bones or pelvic lymph nodes.
While no one is certain why removing the prostate appears beneficial, there are three main theories. The first is that it removes the engine of the disease.
"By removing the primary you are removing cells that could potentially metastasise later. You are removing a sink of metastatic clones," he says.
Second, by reducing the volume of disease, systemic treatments might be more effective because they have fewer cancer cells to fight. This means men might respond better to drugs.
Third, it may be that removing the primary tumour provides good local cancer control. As the man's cancer progresses, he is less likely to be worn down by repeated hospitalisations to relieve bladder problems, remove obstructions or stem bleeding.
Treating primary tumour
Professor Eastham notes that treating the primary tumour is the standard in many cancers including those of the lungs, kidneys, breast, ovaries and bowel.
Even if bowel cancer has spread widely, the primary tumour is removed to ensure the colon is not obstructed. This is called "debulking'' and while it is not curative, it can make the person more comfortable and extend their life.
Asked for a thumbnail sketch about the kind of man who might benefit from surgery, Professor Eastham said this individual would typically come to Memorial with a PSA of nine.
PSA, or prostate specific antigen, is a protein released into the blood by the prostate and is used as a marker for cancer. It's not greatly accurate but is the best available.
On biopsy, this man will have evidence of high grade cancer. Measured on the Gleason Score, he'll have an eight or nine.
On a scan, he'll likely have one or two bone "mets", perhaps in his hip.
Five years ago he would automatically have been prescribed hormone therapy.
Today, he would likely be started on hormones and have his "mets" spot welded with radiation to try to get rid of them. Then he would have his prostate removed or radiated.
He would continue on hormones for about 12 months and then stop all treatment.
Trying to prevent complications
"While his cancer might recur, he will stay off hormonal therapy for a prolonged period and enjoy improved quality of life. Our aim is to limit and delay the need for other therapies and to prevent complications from local tumour growth," says Professor Eastham.
"If I were in this situation, I would absolutely have my prostate removed."
He emphasises this protocol does not apply to men with big, bulky prostates that have grown into the rectum or bladder.
It is for men who would otherwise be suitable for a radical prostatectomy but have a small number of bone or node "mets".
He also emphasises this is not standard of care and until the evidence is mature, it is only being used in fully informed, carefully selected men.
While there have been a number of small promising studies, some large international prospective studies are now under way to confirm whether this approach does increase survival and to determine the best combination of treatments. One of these trials is at Memorial.
"We are all looking for that home run, that combination of treatments that can cure men who have previously been incurable," he says.
'Fundamental change'
Peter Heathcote, the new president of the Urological Society of Australia and New Zealand, says this new thinking represents "a fundamental change".
But he says the data has been thesis generating and is not strong enough to be included in best practice guidelines. He would like to see trials in Australia too.
While radiation is increasingly being used at this stage, Dr Heathcote says the new thinking is really about surgery.
"Personally, I have shifted in the last decade. Before then I wouldn't have countenanced aggressive local therapy, radiation or surgery. Now I would definitely offer radiation to the primary together with hormone therapy.
"And in the last two years I have begun offering surgery, mainly to younger men, with low volume disease who have responded beautifully to hormones. I think 'well this guy is going to be around for a long time, surgery may do him some good' but there is no certainty about it."
As this "guy" would otherwise have been on hormone therapy, the impact of surgery on his potency would be less of an issue. There would, however, be a risk of continence issues as there are with any man who has his prostate removed.
Questions of quality
But Dr Heathcote is interested in how this new approach can improve not only the quality of a man's life but the quality of his death too.
He says about 30 per cent of men with metastatic disease and an untreated prostate are likely to be in crisis towards the end, going in and out of hospital because they are passing blood, need emergency radiotherapy or semi-urgent procedures to relieve their obstructing prostate.
This can be difficult to manage, painful and debilitating. It's also distressing for the family.
"It could be that a radical prostatectomy would have helped them avoid this terrible morbidity at end of life and, as well, possibly increased their longevity," says Dr Heathcote.
For all those Australian men who have had a radical prostatectomy only to discover down the track that they still have cancer, this new thinking may bring consolation and some hope.
"When the clinical guideline on locally advanced and metastatic prostate cancer was developed in 2010 there was insufficient evidence to support the use of surgery in men with advanced prostate cancer," says Associate Professor Anthony Lowe, of the Prostate Cancer Foundation of Australia.
"The picture is rapidly changing and there is emerging evidence that some men may live longer and have a better quality of life from debulking the cancer. It would be great to see clinical trials here in Australia to establish the benefits."
*Jill Margo is an adjunct associate professor at the University of NSW
