AMA Spokesman: 50% of PC Treatments Unnecessary

In the news about Angelina Jolie's mastectomy was this information from Otis Brawley, Chief Medical Officer for the AMA: "Among prostate cancer survivors, about half of those treated 'would not have been bothered by the disease' if they had not had been diagnosed in the first place, Brawley said." Really? I thought studies had shown overtreatment to be in the 8-16% range.

Phenom,

NIH in their consensus statement said...
More than half of cancers detected with PSA screening are localized (confined to the prostate), not aggressive at diagnosis, and unlikely to become life-threatening. However, 90 percent of patients receive immediate treatment for prostate cancer, such as surgery or radiation therapy.

An analysis of autopsy studies has shown that approximately one in three men over the age of 50 years had histologic evidence of prostate cancer, with up to 80% of these tumors being limited in size and grade and, therefore, clinically insignificant. A recent study of incidental prostate cancer diagnosed in organ donors found prostate cancer in 1 in 3 men age 60-69, and this increased to 46% in men over age 70. Currently, the lifetime risk of being diagnosed with PC is 16%. Fortunately, the lifetime risk of prostate cancer death is only about 3%.

Overtreatment may be much higher than the NIH estimate. A Swedish study tracked men who were diagnosed with PC before the PSA era. They found that after 30 years of tracking, and only palliative treatment, only 17% had died of PC. Presumably, most of the men in their study would have been diagnosed earlier if there had been PSA screening. And many more men would have been asymptomatic throughout the lifetime course of their disease, and would never have been identified as having it.

Natural History of Early, Localized Prostate Cancer: A Final Report from Three Decades of Follow-up

The best evidence we have of overtreatment is the PIVOT study. The study began with screening of over 5000 men starting in 1994 and continuing for almost 10 years. After screening and obtaining informed consent, they had 731 men with localized PC, under 75 y.o., and PSA<50. Half were randomly assigned to be treated with surgery and half just watched, some of whom were followed for over 15 years -- a very big, expensive study. This was begun at the beginning of the widespread PSA-testing era. Surgery was then the best treatment around, and although there have arguably been improvements in ameliorating some of the side effects of surgery, the cure rates are pretty much the same. The age groups are very representative. They matched the treatment and the control groups across several age categories, race, risk category, Gleason score, PSA, co-morbidities and health status. If they tracked any quality of life measures, they haven't yet reported it.

The results show no overall benefit in terms of all-cause survival or in prostate cancer-specific survival from treating with surgery. After an average of 12 years, 5.8% of men who were surgically treated had died of PC, and 8.4% of men who were observed but not treated- a difference that is not statistically significant. This was also true within all age and race categories, Gleason scores, and health status. The only categories that showed slight benefit in cancer survival (but not with statistical significance) was among those with high risk PC and with PSA greater than 10. I suspect that if they had included adequate radiation treatment for high risk PC rather than surgery, the result might have been more robust. Their conclusion is that there is so far no survival benefit to treatment at all. But perhaps a benefit will emerge after only 20 years, especially among those diagnosed with high risk PC or higher PSAs.

Here's what was presented to the AUA in 2011:

Prostate Cancer Intervention vs Observation Trial (PIVOT) - AUA presentation

There seems to be a whole lot of overtreatment going on.

Post Edited (Tall Allen) : 5/15/2013 9:46:48 PM (GMT-6)

i had this discussion with Brawley via email. Was very surprised he responded to one of my emails let alone multiple ones. He admitted to me that this position is related to mean of an average age of 67.

That is a whole quarter century more than me (us).

He said that studies for our age group should be done but that that wasn't his focus.

In other words, it's not even remotely pertinent to many of us.

Sure, wouldn't argue with him that a 75 year old might not need treatment, bit that is neither here nor there for guys like me.

Brawley has no place being so prominent in this debate.

With the greatest of respect to those on this forum battling serious and advanced prostate cancer issues, it appears that many of us simply have been had- unnecessary treatment with the vicious and life altering side-effects of ED and incontinence--- we were strangers and they took us in-

I knew what the SE's could be going in. So far I only have one, ED, but I'm only 54 days out from surgery too.
That's why it took my baby ass 5 years to do anything about it. lol

The results of the PIVOT study are stunning, really. No benefit from treatment. Period. Wow. What about longer out than 12 years? Did they report on the longer term? Could it be that it doesn't matter what you do, if you have the marker(s), your G7 will go on to kill you, and if you don't, your G10 won't? I assume no G6s should ever do anything, and maybe nobody should ever be treated at all because it just doesn't make any difference. What about salvage treatments for advanced PC? Do they add longevity, or are they, too, useless? Are there studies that dispute the PIVOT findings? It does defy common sense in a way. Here you have a cancer that kills a lot of men through metastasis, and you'd think removing the source of the cancer before it metastasizes would be a good idea. And what does account for the steep decline in PC mortality in the last 20 years, if not treatment? If all this is true, at least I can stop worrying about whether my PSA is rising and the cancer recurring. If it never mattered in the first place, surely it doesn't matter now, either.

men don't need it UNLESS THEY ARE VERY YOUNG

www.youtube.com/watch?v=mhL3pMdNgNU

PIVOT showed no benefit whether men were under 65 or 65-75. However, because 90% of men diagnosed with prostate cancer are over 60, and the PIVOT trial only watched men with diagnosed PC, it has little to say about men who are diagnosed at a very young age. It is unknown whether treatment would benefit them.

The ProtecT study going on now in the UK is a randomized control trial of about 110,000 men between the ages of 50-69 who were detected with PC (UK does not have PSA screening) and are randomly assigned to prostatectomy, radiation or active surveillance.

I'm not aware of any randomized controlled trials looking at men under 50 years of age.

Phenom, we now know that to be true out to about 15 years, especially if you're diagnosed at an early stage.There may be select sub-groups who may benefit from early treatment, but we don't yet have data to substantiate that.

Now that the AUA is on a roll about shared decision-making, I'm hoping their next issued guidelines will be about treatment. If their treatment guidelines are consistent with their screening guidelines, then sharing this information should become standard.

Do you think that if you knew about this before you were treated, you might have made a different decision?

I just watched the online presentation of the pivot study and it's clear to that the study needs to be interpreted very carefully.

As I see it...

The study DOES find that if a 68 year old patient is in the D'Amico low risk category, and/or has a PSA under 10, that treatment makes little difference to whether he dies of PC.

But if the patient has PSA greater than 10 or is in the D'Amico high risk category, treatment makes a great deal of difference. For a patient in the high risk category, the 10 year risk of dying of prostate cancer is reduced by 64% (that's right, nearly 2/3) by treatment vs. no treatment. Now, the study says that this difference was "not significant". How can it be so big an effect and still be "not significant"? The answer is that the sample size is too small for it to be significant regardless of the size of the effect.

Here's why size matters: about 365 patients were enrolled in each of the two arms of the study (one arm being RP the other arm being AS.) about 21% of each were judged to be in the Amico high risk category, or about 72 in each group. about 42% of those in the AS group were dead by the end of the study (about 30 deaths), but only about 17% of those in the RP group were dead (about 12 deaths). But the difference in the number dead, in absolute terms, is only 18 deaths -- and that number of deaths is way too small to be "significant" in statistical terms. But the trend is strong, as shown by the HR numbers, and in a larger study would have clearly been significant, as the authors themselves imply in their conclusion.

So the study DOES suggest that 68 year old patients with low gleasons or low D'Amico risk scores are being overtreated if they are given surgery (how likely is that?).

The study DOES suggest that 68 year old patients with D'amico high risk tumors (maybe even intermediate risk) or high PSA (>10) are NOT being overtreated, and that RP helps, even in these older patients.

The mortality curves are generally upward-sloping at the end of the study period, indicating that had the study continued, the effect of treatment would have been more dramatic.

The study says NOTHING about the value of treatment for younger men. But clearly if you connect the dots, the study implies that younger men (<68) with intermediate or higher risk disease benefit from treatment.

Due to the sample size issue, absence of significant evidence is not evidence of absence. As always, it's dangerous to over-generalize from the headline of a study. It is often fatal.

I didn't say "don't question" the experts. If I didn't, I would have gone with the guy who had 400+ procedures or with the guy at Mount Sinai that does BT. You should read more carefully. Of course experts differ in their opinions, that's why it's good to listen to as many experts a spossible without thinking you're actually an expert.

You know, I know a lot about guitar playing, but when in a room with Buddy Guy and Eric Clapton I shut up and listen and ask only good questions if they come up. I know a ton about tennis, but when stuck in an airport waiting room with Ilie Nastase I shut up and listen.

Yes, you might have gone for AS and you regret not doing so, I get it, you know why? Because I'm an expert on human nature :)

davidg said...
I knew that I did not want to monitor it and get overly intellectual about it and question the actual experts.

davidg said...
I didn't say "don't question" the experts. If I didn't, I would have gone with the guy who had 400+ procedures or with the guy at Mount Sinai that does BT. You should read more carefully.

RalphV,

Until we get better information, as I hope we will from the SelecT study, the PIVOT study is the best we have to compare treatment to observation. Slide #25 shows that 21/364=5.8% of the men who had surgery died of PC within the median of 12 years, while 31/367=8.4% of the men who were on watchful waiting died of PC in that time frame. The difference of 2.6% was no where near statistically significant . One cannot draw inferences of what might have been if there had been more people in the study, and one cannot pretend there is a real difference when there isn't. Out to 12 years, it's the only randomly controlled clinical trial we can bank on.

The authors of the PIVOT study said...

In men with localized prostate cancer detected during the early PSA era, radical prostatectomy compared to observation produced reductions in all-cause and prostate cancer mortality that were not significant and less than 3% in absolute terms through 12 years.

Thank you for reminding me of the details of the study, which I know. But I guess I missed your point -- how does any of that change any of the conclusions or in any way invalidate it?

I wasn't at all comparing the PIVOT study to the Swedish study. What I was doing is presenting the findings of the Swedish study (the longest time frame one I know of) to show that PC has a very long natural history and only a small percentage of men who get it are likely to ever die from it. Only 17% of men who had actual symptoms (not just high PSAs) ever died from it. I pointed it out because Phenom raised the question about overtreatment. Clearly, if a vast majority of us will never die from the disease, as the Swedish study shows, and if 90% of the men with it get radical treatment for it, then most of us have gotten possibly harmful treatment that we didn't need. Figuring out which needed it and which didn't is the challenge.