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TWO major studies on treatment versus no treatment for prostate cancer challenge wide-held beliefs.
The availability of prostate specific antigen (PSA) testing from the early 1980s has led to many of us men over 40 years being diagnosed with early stage abnormalities of the prostate.
We are then influenced by endless media reports and testimonials from high profile celebrities to undergo surgery and to “get rid of the cancer”. We are presented with a terrifying agenda: unless you get immediate treatment, the cancer will rapidly kill you. To this is added the by now standard choice of whether you want to put up with a bit of impotence and incontinence to live long enough to be there to see your children and grandchildren grow up and get married.
In addition, some urologists highlight the contested benefits of robotic surgery and quick recovery times, implying that soon you will be back playing golf and getting on with life. You are anxiety free in the belief that the cancer is gone.
Such media-driven infomercials are testimonial-heavy and science-light. They stand in stark contrast to the actual clinical evidence, which is that most prostate cancers take decades to exit the prostate and most men will usually die with, but not from, prostate cancer. Autopsy studies show prostate cancer in up to 40% of men in their 40s and 65% of men in their 60s but only 3–4% of Australian men actually die of prostate cancer at a median age of 82 years.
Two recent clinical trials, Prostate Testing for Cancer and Treatment (ProtecT) and Prostate Cancer Intervention versus Observation Trial (PIVOT), completely undermine the stratospheric spin associated with prostate cancer being a death sentence. They are unambiguous in their implications.
The bottom line? Men with early stage abnormalities of the prostate who do not undergo surgery or radiation treatment, but whose condition is monitored for any progression of the cancer, live just as long as men who opted for complete removal of the prostate and who now live with its immediate consequences, including incontinence, intimacy issues, bowel problems and intervention regret.
The hard evidence
In the ProtecT trial, three groups of men were assigned to either surgical removal of the prostate, radiation treatment or active monitoring. The groups consisted of 553, 545 and 545 men respectively. After a median of 10 years, the total number of deaths due to any cause was 55, 55 and 59 years respectively in each group. Thus, 90% of men were still alive after this 10-year median follow-up, including men who did not receive any radical intervention. Although surgery and radiation delayed local progression and the development of metastases in some men compared with monitoring (46 patients versus 46 versus 112), the number of deaths definitively attributable to prostate cancer in each of the groups was low, only 3, 4 and 7 deaths respectively. These data do not require high level statistics for their interpretation. The odds of dying specifically from prostate cancer in this well managed trial were less than 1%.
Now comes the latest PIVOT trial update, published last week, where two groups of men were assigned to either surgical removal of the prostate or active monitoring. The groups consisted of 364 and 367 men respectively. After nearly 20 years of follow-up (median of 12.7 years), the number of deaths due to any cause was 223 and 245 respectively in each group. So once again, nearly the same number of men in each group were still alive after nearly 20 years. Surgery reduced disease progression, which was mainly local recurrence or the development of asymptomatic biochemical recurrence. It did not significantly prevent overall deaths or deaths due to prostate cancer any more than active monitoring.
It is striking that the number of deaths definitively attributable to prostate cancer in the two groups was only 18 and 22 respectively. This means that the odds of dying specifically from prostate cancer at a median of 12.7 years after a PSA-generated cancer diagnosis were of the order of 5% for the surgical group and 6% for the active monitoring group.
The clarity of the above evidence is stunning.
As the lead author of the ProtecT study, Dr Hamdy of the University of Oxford has pointed out: “There’s no hard evidence that treating early disease makes a difference”.
The survival from prostate cancer is so high that it is not a question of deciding which treatment is best, but whether any early radical treatment is required at all. The current position has been clearly articulated by Dr Otis Brawley, the Chief Medical Officer of the American Cancer Society and an expert on prostate cancer screening, who pulls no punches: aggressive PSA screening and treatment have resulted in more than 1 million American men getting needless treatment.
Thus, every patient now has a choice based on hard evidence. If they are anxious or if family or peer pressure is high, undergoing surgery means that their chances of dying from prostate cancer are near identical to not taking that option. However, there are serious downsides that will affect quality of life for decades to come. Patients who have undergone surgery are four times more likely to require absorbent pads for incontinence and three times more likely to have erectile dysfunction. These are not problems that are routinely highlighted.
The future
At the moment, the latest DNA research has had minimal impact on how to tell whether an early stage prostate cancer will grow ever so slowly, or whether it will become aggressive and spread outside the prostate and lead to death from metastasis.
The current evidence is that the future behaviour of any cancer is decided very early and diagnosing it early and actively monitoring its progress will have no effect on outcome. The key problem is that growing human prostate cancer cells in dishes, or in mice, is far removed from cells growing in a prostate. Mice are not small humans and their prostates, hormonal balances, diet and genetics are quite different. Likewise, while magnetic resonance imaging will localise abnormal sites in a prostate gland with excellent precision, it cannot as yet distinguish between the potentially dangerous and the indolent cell populations.
Therein lies the rub.
The implications for all of us now
The reality is that we have reached the absurd situation where media opinion, fearmongering and social pressure still trump hard evidence, but at least some clarity has emerged from the latest trials. Nevertheless, it will still be a struggle for doctors to explain to men that certain cancers just don’t need to be treated immediately.
We already do it for early-stage chronic lymphocytic leukaemia, many low grade non-Hodgkin’s lymphomas and slow-growing lung or renal cancers in elderly patients, so it can be done.
It will be even more difficult to dislodge early PSA testing, particularly in countries such as the United States, where it has now become deeply entrenched in a belief-based or business enterprise. After all, given the huge investments in proton-based radiation facilities (where it costs in excess of $300 million to just build a proton beam facility), or in robotic surgery machines, the financial incentives to repay the investment and to move to a for-profit situation are huge. A constant supply of patients is obligatory, and an increasing supply is preferable.
For the moment, the first step must be to educate physicians so that they can provide full disclosure to any current patient of the mature results of the ProtecT and PIVOT trials.
Similar to countless past treatments, such as radical mastectomy for breast cancer, lobotomy for mental illness and stomach surgery for ulcers, it is now abundantly clear that radical prostatectomy, robotic or otherwise, for early-stage prostate cancer is becoming outdated.
Associate Professor Ian Haines is a medical oncologist and palliative medicine specialist practising in Melbourne. He is also affiliated with Monash University and the Alfred Hospital.
Dr George Miklos is the founder of Atomic Oncology (www.atomiconcology.com).
To find a doctor, or a job, to use GP Desktop and Doctors Health, book and track your CPD, and buy textbooks and guidelines, visit doctorportal.
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International Conference on Women’s Health and Breast Cancer (Women’s Health Asia Pacific 2018) extends its welcome to you during November 19-20, 2018 at Sydney, Australia with a theme ”Challenges in targeting Cancer and its Therapeutic Advances and Wellness of Women”.
“Sooner or later we should be able to tell which prostate cancer will be a lethal one and which ones will be harmless”
But much more importantly, we need to be able to tell what treatments will provide benefit and what treatments won’t. Detection itself is not enough.
The sad history of PSA screening shows that most people don’t understand the importance of treatment needing to produce a benefit.
In reply to Louis on July 31, we said “up to 40% and 65%” respectively. We took our figures from Table 3 of the article and these figures were from the USA where we considered the data were likely to be very accurate. Their incidences were higher than other countries assessed. We agree that the average of all countries combined on the graph in Figure 2 is as you stated.
The devil is always in the detail. The inability to recognise this highlights a lack of academic rigor in the authors’ assessment of the PIVOT and ProtecT studies. Both of these studies were conceived well prior to the era of active surveillance and the high uptake of acceptance that aggressive treatment of low risk prostate cancer was inappropriate. The majority of men in both of these studies are men who should not have been offered treatment in the first place. Hardly surprising that both studies failed demonstrate differences in mortality. There is a convenient exclusion of discussion of the SPCG4, whilst prior to the PSA era, studies a group of men with significantly more aggressive cancers than PIVOT and ProtecT, and does demonstrate a striking difference in prostate cancer specific mortality. Let’s not throw the baby out with the bathwater on this.
what percentage of men in the “monitor” group went on to have some sort of intervention procedure done and what was the investigation that influenced the need for intervention?
PLEASE ALL READ THE REVIEW OF THESE TRIALS ON MEDSCAPE – you have not looked at the population tested in PIVOT (veterans over 65-70 at enrolment!), so the data is NOT convincing! These men already had mostly slowly progressing disease according to their scores, other morbidities etc etc. It certainly should NOT be extrapolated to younger men with biopsy-proven disease, nor ESPECIALLY to higher risk groups!
I agree that early surgery is inappropriate for many men, but until we have better indicators as suggested by David Yana above, we are going to have these back and forth discussions about testing, treating or watching. It is very difficult to get ANY patient past the C-word without discussing surgery as the front-runner – that is what patients expect for most such diagnoses. But it is the preamble to even testing, and when, given our current knowledge limitations, which remains the essential first step in this process. So define the literacy of the patient/partner/carer in front of you FIRST before embarking on any journey down this bumpy road of prostate cancer investigation, diagnosis and management. Unfortunately, I do NOT believe that the PIVOT Trial, (in particular) adds anything useful at this time. I beg to reserve judgement on PROTECT! Others more experienced in this field may choose to differ, as the authors of this article obviously do.
The decision for treatment should go before a multidisciplinary committee with a specific statistical estimate for that patient based on the best data, vs ” what I like to do in theses situations”.
It may come to pass that the consult to see a surgeon/ treatment option should be done only if the patient has decided that he wishes to proceed that way.
The days of personal opinion are fading.
This will become the case for many patients with multi co-morbities.
The ” new studies” will be based on a population of “N=1” , and how we add up the benefits and costs of treating a specific illness, in a specific patient will become increasingly out of the hands of the individual crafts apart from the most straightforward of patients and diagnoses
If you are going to advocate for not doing PSA’s and not actively intervening, then you owe all of the profession a way to do it safely.
You also should provide accurate information. 40% of men in their 40’s and 65% of men in their 60’s did not have prostate cancer at autopsy in your linked reference. It was 15% and 30% approximately, as I would expect as a GP who believes men’s health needs rational and not just political attention.
As far as “3-4% of men actually die of Ca prostate at median age 82”, you could also interpret the summary graph in the link to indicate more men die of prostate cancer than women of breast cancer. Neither would tell the story accurately.
A raised PSA test does not mean referral for surgery or nothing else. Just like knee MRI in the over 40’s can lead to unnecessary and inappropriate surgery, it can also assist in the diagnosis and appropriate treatment of active pathology. You don’t die of untreated OA of the knee, but your death from untreated and aggressive Ca prostate is nasty.
In this era of logic about the meaning of PSA changes and MRI Staging of prostate pathologies, surely we can do better than slagging urologists who do their part in treating a disease that is of great concern to us men.
I am a GP Over the years I have treated quite a few patients with prostate bone secondaries. Not a very pleasant disease !. If it was possible to assess early stage prostate cancer and be sure which is aggressive and which can be watched , I would agree to wait and watch., otherwise the sooner the operation , the better re prevention of spread.
For the few who would loose their sex life or need a pad, it s abetter choice than missing the boat., getting bone secondaries, and dying much younger.
Sooner or later we should be able to tell which prostate cancer will be a lethal one and which ones will be harmless .