Last October a very important prostate cancer study was reported with surprisingly little fanfare. It reported the first results from the ProtecT study, one of the largest and most expensive studies in the history of prostate cancer.
It all started nearly 20 years ago, soon after PSA testing became generally available in the UK. PSA testing was resulting in more men being diagnosed with prostate cancer. Lots of these men were getting radical treatments (radiotherapy or surgery) with all the associated side-effects. Some surgeons and radiotherapists were gung-ho, saying it was a good thing and that anyone with cancer should have it removed. “What’s the problem – we’re curing lots of men with prostate cancer!”
But the real question was whether the men needed to be cured with radical treatments. There was no major change in death rates due to prostate cancer and most men die with, rather than of, prostate cancer. Some people argued that active surveillance was the best treatment. Active surveillance means monitoring the cancer in case it progresses.
So, some of the best urologists, radiotherapists and statisticians in the UK got together and designed ProtecT. The trial cost squillions. Expectations were controlled at the outset – no results would be published for at least 10 years. Finally in 2016 the first results were published in the world’s number one medical journal (reflecting the importance of the work), the New England Journal of Medicine, on October 13, 2016.
The trial was mega-big. 2,664 early (and some late) prostate cancers were discovered as a result of PSA tests in 82,429 men aged 50-69. These are the men who are young enough to potentially benefit from radical treatment, i.e. they could live long enough for the treatment to prevent them dying of prostate cancer.
About two-thirds of the men diagnosed agreed to take part in the trial. This was one of the greatest achievements, because many people believed that it would be impossible to persuade men to agree to be randomised to a “no treatment” group.
Men in the active surveillance or “no treatment” group did find it tough, particularly as they were subjected to PSA tests with all the associated stress every 3 or 6 months. Not surprisingly, many men in this group changed their minds and opted for radical treatment later. Luckily, this did not cause any major problems.
545 men were assigned to active surveillance, 553 to radical surgery and 545 to radical radiotherapy.
10 years later only 17 of the 1643 had died of prostate cancer – about one in a hundred.
There was no statistical difference in death rates due to prostate cancer between the active surveillance (8), surgery (5) and radiotherapy (4) group.
Overall, 152 men died of other causes. About 10% – what one might expect over a 10 year period for men with a median age of 62.
However, men on active surveillance were more likely to develop metastases over the 10 year period. The figures were 33/545 (6%) men in the active surveillance group, compared to 13/553 (2%) in the surgery and 16/545 (3%) in the radiotherapy group. So, 10 years is too early to know if survival will be worse in the active surveillance group. None of these men with metastases can be cured, but they may die of other causes before the prostate cancer kills them. Perhaps, after 15 or 20 years follow up, it will be possible to prove that radical surgery or radiotherapy saves lives, but it won’t be many and it may be hard to reach statistical significance.
A parallel paper in the same journal looked at the side-effects of the three treatments over the first 6 years. This study is less clear cut, because the results are reported on the basis of intention to treat (usually the correct approach), rather than actual treatment. The results are muddied by the fact that over half the active surveillance group went on to receive radical treatment during the 10 year period and 15% of the men assigned to surgery or radiotherapy did not receive it. Also, because the men were in a trial, they probably had more opportunity to deal with the side-effects. The only major conclusion is that surgery caused more sexual dysfunction and urinary incontinence throughout the study.
So, if you are a man with early prostate cancer detected by a PSA test, you only have a 1% chance of dying of prostate cancer in the next 10 years whether or not you have radical surgery or radical radiotherapy. If you think you’ve got more than 10 years left, chances are radical treatment will reduce your risk of death from prostate cancer very slightly, but we’ll have to wait another 5-10 years to be sure.
Another conclusion that some people might draw from the study is that PSA screening may cause more harm than benefit. It promotes stress and anxiety and we may be better off without it in the setting of prostate cancer diagnosis. The UK and US governments are adamant that there is not enough evidence to support its use for screening in the general population.