The question whether widespread use of the PSA test to test for risk of prostate cancer has a significant impact on prostate cancer-specific mortality continues to be highly controversial and to engender strong emotions among many medical professionals, patients, and prostate cancer advocates.
A newly published study by Outzen et al., in the journal Acta Oncologica, reports on an analysis of data from the national Danish Cancer Registry and Register of Causes of Death over the period 1978 to 2009 and includes all cases of prostate cancer and all deaths of men diagnosed with prostate cancer during this study period.
The authors report the following:
- During the 5-year period from 1978 to 1983, the age-standardized incidence of prostate cancer diagnosis in Denmark was 29.2/100,000 person-years.
- During the 2-year period from 2008 to 2009, the age-standardized incidence of prostate cancer diagnosis was 76.2/100,000 person-years.
- The increase in the incidence rate
- Became evident in the mid-1990s (corresponding to the increase in the use of PSA testing for risk of prostate cancer)
- Has been most pronouced among men of > 60 years of age
- Was highest among men born between 1943 and 1947
- The prostate cancer-specific mortality rate in Denmark has remained ”largely unchanged” over the entire 30-year study period — at about 19/100,000 person-years.
- In 1998, there was a significant change in stage distribution, and an increasing percentage of prostate cancer patients were being diagnosed with localized disease
Outzen et al. conclude that:
- “The observed increase in [prostate cancer] incidence during the period 1993-2009 in Denmark may be attributed primarily to increasing unsystematic use of … PSA … testing.”
- ”… there is not yet any major influence of intensified PSA screening and more frequent use of curatively intended therapy on the overall prognosis of [prostate cancer].”
[Editorial comment: Please note that the emphasis on the word "yet" in the quotation immediately above has been added by the editors and did not appear in the original.]
The “New” Prostate Cancer InfoLink is very conscious that a lot of people will not be enamored of these study results. However, please be aware that we are simply reporting the findings of a group of Danish investigators from a very highly structured data registry. Don’t blame the messenger!
Is it possible that a mortality effect might emerge in Denmark over time? Yes it is. Some are going to argue (with a degree of justification) that until some 20 years after the majority of men in Denmark are being diagnosed with localized disease (i.e., in 2018), it is actually unreasonable to expect to see a meaningful impact on prostate cancer-specific mortality. Conversely, the lack of any meaningful impact on prostate cancer-specific mortality over nearly 30 years tends to suggest that any meaningful impact is likely to be small if and when it does appear (which again raises the question of whether the risks justify the benefits on a national basis).
Filed under: Diagnosis, Living with Prostate Cancer, Risk Tagged: | benefit, Denmark, incidence, mortality, PSA, risk, screening
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The more frightening half of this finding is that treatment advances have not shown benefit either. How far back do you have to go to find treatment of any kind extending life? Does the whole treatment spectrum stand up to the current methods of evaluation?
Metastatic prostate cancer spreads before PSA or DRE detection is the logical conclusion. No treatment actually has benefit on a lethal cancer is the other logical conclusion. These conclusions are true even if you set aside the large pool of moderate risk cancers. Offsetting these is the probable increase of prostate cancer being listed as the cause of death after the diagnosis. A death which, in the absence of a PSA test, would have been old age, gets the prostate cancer tag. Pure speculation on my part.
Dear Sitemaster,
Quality data are necessary to develop quality studies. The reported fundamental numbers from the Danish study are much different from the US SEER data. Without having the complete data set from the Danish investigation there are more questions than answers.
– Is there a genetic factor?
– Is the treatment modality ineffective?
– Do other disease risk mortality increase?
– Was detection followed by treatment?
To conclude a PSA benefit or not we need more information.
Knowledge is king
Fred Kinder
Dear Mike,
Your are correct, many treatments have shown little improved mortality or quality of life over the last 50 years. However in the last 10 years the bar has been raised for cure (biological control) and patient quality of life outcome.
Men must do the research to understand the science and evidence for each modality to select the modality that offers them the best outcome.
Regards,
Fred Kinder
Thank you for the news.
Dear Fred:
As far as I am aware (which is not the same as “perfect knowledge”):
– There is no genetic factor (and Denmark, like most other western European nations, has developed a highly genetically mixed population over ther past 1,000 or so years).
– The same treatment modalities used in the USA have been availble in Denmark for all of the past 30 years (along with some that we don’t have, like HIFU).
– Danish males actually have a life expectancy that seems to be very closely comparable to that of American males.
I can’t tell you whether “detection was followed by treatment”; nor can I tell you whether detection was followed by treatment that was necessary and effective (but then no one can tell you that for men in the USA either). What I can tell you is that early detection of prostate cancer would be pretty pointless if one did not intend to follow it by treatment in men who one belived to have clinically significant or potentially clinically significant disease.
Feel free to go do some homework to find out. I’m just reporting data.
A question that always arises in my mind whenever I see figures like these, is “Are the cases of mortality strictly those who were known to die of prostate cancer?” How about others in the prostate cancer numbers that died of other complications … were those complications brought about because of the effect prostate cancer was having on the patient? If so, there are other mortality numbers that should be added because the complication that caused death was attributable to the effect prostate cancer was having on the patient.
Dear Chuck:
One can also reverse that question and ask whether men currently being assigned prostate cancer as a cause of death are actually dying of other conditions which, while quite common among men with prostate cancer, are not necessarily induced by prostate cancer. We are never going to know accurate answers to questions like this, however. Medical opinion immediately following the time of death is the only criterion for assignment of cause of death unless a full autopsy is conducted — and even autopsies can be far from accurate.
Dear Sitemaster…..I thought I was the only guy on my computer 24 hours a day including weekends…..grin….
Chuck: Naah … not even close! :O)
According to this paper by Bouchardy et al., Denmark is one of the EU countries in which prostate cancer mortality has continued to increase. When PSA detects prostate cancer, some patients need treatment. If patients are screened but not treated, mortality tends higher. …
Ralph:
The paper by Bouchardy et al. is based on data from 1975 to 2001, whereas the paper by Outzen et al. is based on data from 1978 to 2009. Also, I cannot tell exactly how Bouchardy et a;. were assessing mortality rates, but it does not appear to be on the basis of age-adjusted deaths per 100,000 male population, so I am having a hard time knowing if we are comparing apples to apples. However, as I pointed out in the article, “yet” is a critical aspect of this analysis.
Mike,
Denmark continues to have a high prostate cancer mortality. Here’s a quote from a more recent paper by Adami et al.:
“The slight decrease in PCa mortality from 1995 to 2006 observed in Finland and Norway deserves mention because a similar pattern was not observed in Sweden and Denmark.”
Even if they are testing more with PSA but end up not treating those men, the result is a flat trend in prostate cancer mortality mortality.
Ralph:
I’m not arguing with you. I just don’t know if we are comparing apples to apples.
Mike,
There is no argument. Outzen’s argument is that there has been an increase in incidence (caused by an increase in PSA testing) but no reduction in prostate cancer mortality. Therefore, screening is useless. I think the reason is because they are conservative in their treatment. It be interesting to know how many of those screened are treated with intent to cure.
Ralph:
Where do Outzen et al. state that PSA screening is “useless”? What they say is that there is no evidence of mortality benefit yet. Danes may well be conservative in their approach to treatment. That’s a national choice (which may or may not be a correct one).
Mike,
No need to say it as long as they do not treat. Otherwise how to explain the mortality reduction in other countries that do treat …
Ralph:
As we have discussed before, that kinda depends on the relative value men place on an extra 3-4 months of life compared to 15 years of life with reduced erectile function and a dripping urinary tract. I am not suggesting that there is a right or wrong here. But if treating most men less lowers mortality less but increases quality of life …? This is, after all, exactly what the PIVOT data may imply.
Different strokes for different folks. There is a whole raft of data showing that (most?) Americans seem to value “life at all costs” whereas (most?) Europeans seem to value quality of life higher than “life at all costs.” And those data are certainly not limited to cancer (let alone prostate cancer).
I am still in favor of PSA testing. I have the right to know and the right to be treated or not: a decision which cannot be made until you are aware of the disease.
There are lifestyle changes that probably help prostate cancer and certainly help general health. Never hurt in moderation.
If the only difference a PSA test makes is I do things I was planning on doing later, it is a good bargain to me.
Knowledge of prostate cancer should not be a cause of panic; ignorance should. I wish the “knowledge” was more definitive, but it is still far superior to ignorance of your true health.
PSA for knowledge; not panic.
PSA testing (1) saves lives and (2) has reduced the incidence of men being told they have prostate cancer and by the way it is in your bones and you have a year or two on pain before you pass.
(3) PSA screening and treatment are choices. No one is forced to be screened or treated.
(4) Men must own the health care choices we make.
(5) No one seems to consider the quality of life impact of aggressive prostate cancer.
(6) Treatment quality of life varies by modality.
(7) Men must make informed choices and not follow the medical referral system blindly.
Regards,
Fred Kinder
Dear Fred:
I am in 100% agreement with you about items (2), (3), (4), (6), and (7), and my guess would be that so are 99% of the people who read this blog on a regular basis.
I cannot agree with your item (5). There is an enormous literature about and regular discussion of this topic; the D’Amico risk categories were developed precisely to facilitate discussion of this issue. We talk about this all the time, as do others. Men with high-risk prostate cancer generally need treatment early — although unfortunately many of them have progressive disease despite such early treatment.
Re item (1) … Testing of the right people most certainly does save lives. Testing of everyone (mass population based screening) may well save lives … at a considerable cost in terms of diagnosis- and treatment-related morbidity and mortality. Men need to understand this or they will not be able to make appropriately informed choices — see your items (4) and (7), which which I agree,
It is not the PSA test itself that is the cost driver. It is the choices made after the test. The argument against PSA testing is a bit misplaced, that not knowing itself is the cost saver.
Mike:
Who is arguing against PSA testing? The differences of opinion are not about black or white (test everyone or test no one). They are very specifically and precisely about choice … The right of each individual to make a sound personal decision as to whether PSA testing is appropriate for him based on sound, neutrally presented data.
Good insight. I am self pay. I did not make the decision to get a PSA test because of the cost. The lab tech, a cancer survivor, insisted I do it. Because of her insistence, I got my first PSA test in May a year ago. It was 35! It went as high as 98, but I was reacting to it aggressively and eventually determined I had prostate cancer which had gone to the lymph nodes. All the doctors wanted to “cut it out”. Even after I got the PSA down to 0.3, my urologist wants to eliminate the “primary tumor” by HIFU. I asked him what he was talking about since the MRI shows the “tumor” gone completely, and he said, “The prostate gland is the primary tumor.” That may be the current wisdom, but I like my prostate gland right where it is. My PSA tests cost me $7.00 a pop. Why not get one?
FS
Hi Fred,
Hope your PSA stays low; however, at your age it may be very aggressive. Look at all options, technology is improving patient outcome. Look at the risk and benefits of all options including SBRT radiotherapy, etc.
Best Wishes,
Fred Kinder
Sitemaster,
I am guilty of using the term testing when referring to screening. The reasoning behind recommendations to reduce screening seems to be that in order to avoid unnecessary treatment and costs, we must avoid screening.
The true problem is the lack of hard data on who to treat and how to treat them. Well, maybe the true problem is continuing to treat nearly everyone in the absence of hard data.
Screening merely increases the frequency of the dilemma, it does not create it.
Mike:
The problem is more complex than that. It is driven by the fact that most people do not appreciate that, after we get to about 50 years of age, more than half of us are living with some amount of cancer in our prostates. And many of us can live with such cancer for another 30+ years without it having any impact on our lives at all, because it is clinically insignificant. HOWEVER, the moment you say to most people, “You have a very small focus of cancer,” they react as though this is going to kill them … and most specialists in medical law will advise physicians to tell such patients that treatment is a recommended option (because we live in a litigious society).
So … There is an inherent bias leading a lot of men who don’t need either a diagnosis or any treatment to get treated, and for those men (and there are a lot of them), the only real opportunity is a negative one (anxiety on active surveillance or unnecessary harm if they actually get a treatment that they do not need).
I feel obliged to say that the current level of over-treatment is actually outrageous, and I certainly don’t think we can go on justifying this in men over about 65 years of age when you see the data from the Scandinavian trial and from PIVOT that shows no median prostate cancer-specific survival benefit (let alone an overall survival benefit) in men with low-risk disease who are > 65 years of age.
Because of our societal behaviors (not because screening/testing per se is right or wrong) over-use of PSA testing leads to over-diagnosis and then to over-treatment. Our societal behaviors are based on a poor level of ability to make good individual risk decisions when we hear the word cancer. (We have similarly poor levels of ability to make good individual risk decisions about all sorts of things — from getting into a car to the amounts and types of food we eat.)
“So … There is an inherent bias leading a lot of men who don’t need either a diagnosis or any treatment to get treated.”
Indeed, you can’t trust urologists to be unbiased. What are you going to do if you have low-risk cancer and your urologist simply tells you you can get the prostatectomy done in a few weeks? He’s the expert. You’re just an ignorant patient. An opinion from a second urologist is probably the same. Urologists have been doing a bad job. They believe their advised treatments are far more successful than they actually are and that their treatments are far less harmful than they actually are.
Chris:
That is true of some urologists, but not all of them. It is also true of some (but not all) insurance salesmen, car mechanics, bankers, politicians, you name it …. Caveat emptor! (Let the buyer beware!)