Freethought & Rationalism Archive

Dr Rick · 09-15-2002, 09:33 AM

The argument that the medical profession presents evidence in a way that suit its purposes just got a big boost this week.

Published in the most recent issue of the New England Journal of Medicine was a prostate cancer study that demonstrated no significant survival benefit to surgery. Here's the abstract:

Volume 347:781-789 September 12, 2002 Number 11

A Randomized Trial Comparing Radical Prostatectomy with Watchful Waiting in Early Prostate Cancer
Lars Holmberg, M.D., Ph.D., Anna Bill-Axelson, M.D., Fred Helgesen, M.D., Jaakko O. Salo, M.D., Ph.D., Per Folmerz, M.D., Michael H�ggman, M.D., Ph.D., Swen-Olof Andersson, M.D., Ph.D., Anders Sp�ngberg, M.D., Christer Busch, M.D., Ph.D., Steg Nordling, M.D., Ph.D., Juni Palmgren, Ph.D., Hans-Olov Adami, M.D., Ph.D., Jan-Erik Johansson, M.D., Ph.D., Bo Johan Norl�n, M.D., Ph.D., for the Scandinavian Prostatic Cancer Group Study Number 4

Quote:

Radical prostatectomy is widely used in the treatment of early prostate cancer. The possible survival benefit of this treatment, however, is unclear. We conducted a randomized trial to address this question.

Methods From October 1989 through February 1999, 695 men with newly diagnosed prostate cancer in International Union against Cancer clinical stage T1b, T1c, or T2 were randomly assigned to watchful waiting or radical prostatectomy. We achieved complete follow-up through the year 2000 with blinded evaluation of causes of death. The primary end point was death due to prostate cancer, and the secondary end points were overall mortality, metastasis-free survival, and local progression.

Results During a median of 6.2 years of follow-up, 62 men in the watchful-waiting group and 53 in the radical-prostatectomy group died (P=0.31). Death due to prostate cancer occurred in 31 of 348 of those assigned to watchful waiting (8.9 percent) and in 16 of 347 of those assigned to radical prostatectomy (4.6 percent) (relative hazard, 0.50; 95 percent confidence interval, 0.27 to 0.91; P=0.02). Death due to other causes occurred in 31 of 348 men in the watchful-waiting group (8.9 percent) and in 37 of 347 men in the radical-prostatectomy group (10.6 percent). The men assigned to surgery had a lower relative risk of distant metastases than the men assigned to watchful waiting (relative hazard, 0.63; 95 percent confidence interval, 0.41 to 0.96).

Conclusions In this randomized trial, radical prostatectomy significantly reduced disease-specific mortality, but there was no significant difference between surgery and watchful waiting in terms of overall survival.

By way of background, prostate cancer is the most common cancer, exceeding lung, breast, or colon cancer rates. Fortunately, it is usually indolent, or slow-growing. The vast majority of men that have prostate cancer are older; subsequently, their life expectancy is not impacted by their disease

In this most recent study, surgery impacted the manner of death for the participants, but did not prolong life. The study only compared surgery against "doing nothing" and still found no benefit; the role of less invasive radiation therapy, a commonly used alternative to surgery for the treatment of prostatic cancer, wasn't even included in the treatment paradigm.

A companion study in the same issue of the NEJM found no significant beneficial impact from surgery upon quality of life, either.

Here's part of what an accompaning editorial in the same journal opined to us physicians about the findings:

Quote:

How should the results of the Scandinavian study influence the advice we give to patients? Specifically, should no one be followed with watchful waiting? Should all patients undergo radical prostatectomy? The answer to both these questions is a categorical "no." There have always been, and always will be, many men who are best served by watchful waiting. They are the patients who are too old or too ill to survive longer than 10 years. If their cancer progresses to the point where it causes symptoms, there are many ways to palliate the disease. Furthermore, in the era of prostate-specific antigen screening, 10 to 20 percent of men with nonpalpable disease have small tumors and may also be candidates for watchful waiting. Criteria have been established to help identify such men.15 For patients with larger tumors, definitive treatment with surgery, external-beam radiotherapy, or interstitial radiotherapy should be considered. In a young man with localized prostate cancer who is otherwise healthy, total surgical removal is an excellent option, and if it is performed by an experienced surgeon, the patient's subsequent quality of life should be more satisfactory. In an older patient or one with clinically significant coexisting conditions, however, radiation therapy is the best option and has the fewest side effects.

In between these two groups, there are many men who are candidates for either surgery or radiation therapy. During the past decade, substantial advances have been made in the technique of radiation therapy, making it possible to deliver high doses of radiation specifically to the prostate. As a result of these advances, patients with localized prostate cancer now clearly have two good options for treatment: surgery and radiotherapy. The Scandinavian Prostatic Cancer Group trial showed that surgery can reduce the rate of death from prostate cancer, but no similar trial of radiation therapy has been conducted. However, both randomized and cohort studies are being developed to compare radical prostatectomy with external-beam or interstitial radiotherapy. Until those trials have been completed, physicians must fully inform men with prostate cancer about their options and help them select the best specialist for the treatment they choose.

Patrick C. Walsh, M.D.
Johns Hopkins Hospital

Here's the lay press report; notice the quote from the same guy that wrote the professional editorial

Take notice of the headline, too:

Prostate Surgery Can Cut Death Risk
Wed Sep 11, 9:19 PM ET

By JANET McCONNAUGHEY, Associated Press Writer

Quote:

For the first time, a study clearly shows that surgery for early prostate cancer ( news - web sites) can reduce the chance of dying from the disease, cutting the risk almost in half.

The question of whether to remove cancerous prostates in early-stage disease has been debated because the cancer typically grows slowly and strikes older men, who may die of other causes before it spreads.

Moreover, removal of the prostate � a doughnut-shaped gland which surrounds the male urethra � can cause serious side effects, including impotence and incontinence.

In the latest study, conducted on 695 men in Sweden, Finland and Norway, the risk of dying from prostate cancer fell from 9 percent to 5 percent during the six years after surgery.

However, deaths from all causes were similar between the men who got prostate surgery and those who did not. The researchers said it could have been a matter of chance that those who escaped cancer death were somewhat more likely to die of other things.

"We now have better evidence that radical prostatectomy diminishes your risk of prostate cancer recurrence. And so we have a possibility to alter the natural course of the disease by radical surgery," said Dr. Lars Holmberg, lead author for the paper.

A companion study also published in Thursday's issue of the New England Journal of Medicine ( news - web sites) found no difference in quality of life between the groups, though it suggested a longer study might find such differences.

The cancer spread elsewhere in the body in 35 of the men whose prostates were removed immediately, compared to 54 in the "watchful waiting group," Holmberg wrote.

But, although the total number of deaths was slightly lower among the treated group � 53 to 62 � it wasn't a big enough difference to be statistically meaningful, wrote Holmberg, an epidemiologist at the regional cancer center at University Hospital in Uppsala, Sweden.

Dr. Patrick Walsh, director of urology at Johns Hopkins University, called Holmberg's a landmark paper.

"It was surprising to see an effect from cancer deaths so early," he said. "It's certainly too early to see an overall effect on survival," But, he said, he thinks such an effect is likely with longer follow-up.

It may be the first study for any cancer in which patients were assigned at random to get surgery or no treatment � what doctors call "watchful waiting" or "expectant observation," he said.

Walsh is an advocate of early surgery and developed a technique used to preserve the nerves that control the penis's ability to become erect.

And, even if the death rate difference doesn't grow, just reducing the number of deaths from prostate cancer is worth it, he said.

What the study doesn't show is which patients would benefit most and least from the operation, said Dr. John Wasson of Dartmouth University, who believes prostate cancer is an overtreated disease...

The impact has already been felt. If you read the press report carefully, you can pick-up from it that there has been no major benefit to prostate cancer surgery yet found. Most people, it appears, don't read carefully, and unfortunately, the press report is heavily biased. My friends in primary care tell me they've been fielding phone calls from their patients this week requesting prostate cancer screening and/or surgical referral (if they have been living with prostate cancer) because they have just read that "prostate surgery saves lives."

Rick

[ September 15, 2002: Message edited by: rbochnermd ]</p>

Happy Wonderer · 09-15-2002, 09:17 PM

One thing they don't really seem to quantify in this study is the quality of life for the people with the surgery vs. those without.

Assuming that the people without the surgery are likely to end up with full-blown prostrate cancer (and the study shows that surgery does decrease this risk), what do we know about the effects of suffering this cancer? If the untreated group suffers progressively more pain and loss of function over the five years, I'd argue that they were worse off than those who were treated but died of an unrelated sudden stroke five years later.

On the other hand, if the treated group suffers from the effects of surgery for five years and the untreated group dies painlessly and suddenly, that would argue for no surgery.

My point is that in order to get statistical meaningful results, medical studies have to have a definite effect to compare to the treatment. It is much more difficult to quantify quality of life, especially for the elderly population. I think that this can lead to suboptimal decisions. "The treatment keeps you alive, so it is good" -- aside from the fact that it will make you as sick as a dog for the rest of your life. Or in this case, the argument seems to be "the treatment cures the disease but you are so old you are going to die of something anyway, so why bother?"

There is more to life than survival. In my case, I'd probably go for the treatment especially as I consider myself healthier than the average and less likely to die of clogged arteries and the like. (I hope that decision is a long way off...)

HW

Dr Rick · 09-15-2002, 09:49 PM

Quote:

Originally posted by Happy Wonderer:
<strong>One thing they don't really seem to quantify in this study is the quality of life for the people with the surgery vs. those without.</strong>

Those issues were addressed in a companian article in the same journal:

Quality of Life after Radical Prostatectomy or Watchful Waiting
Gunnar Steineck, M.D., Fred Helgesen, M.D., Jan Adolfsson, M.D., Paul W. Dickman, Ph.D., Jan-Erik Johansson, M.D., Bo Johan Norl�n, M.D., Lars Holmberg, M.D., for the Scandinavian Prostatic Cancer Group Study Number 4

Quote:

We evaluated symptoms and self-assessments of quality of life in men with localized prostate cancer who participated in a randomized comparison between radical prostatectomy and watchful waiting.

Methods Between 1989 and 1999, a group of Swedish urologists randomly assigned men with localized prostate cancer to radical prostatectomy or watchful waiting. In this follow-up study, we obtained information from 326 of 376 eligible men (87 percent) concerning certain symptoms, symptom-induced distress, well-being, and the subjective assessment of quality of life by means of a mailed questionnaire.

Results Erectile dysfunction (80 percent vs. 45 percent) and urinary leakage (49 percent vs. 21 percent) were more common after radical prostatectomy, whereas urinary obstruction (e.g., 28 percent vs. 44 percent for weak urinary stream) was less common. Bowel function, the prevalence of anxiety, the prevalence of depression, well-being, and the subjective quality of life were similar in the two groups.

Conclusions The assignment of patients to watchful waiting or radical prostatectomy entails different risks of erectile dysfunction, urinary leakage, and urinary obstruction, but on average, the choice has little if any influence on well-being or the subjective quality of life after a mean follow-up of four years

The two groups (surgery versus waiting) had different problems with the former experiencing much more sexual dysfunction and urinary incontinence, and the latter more troubled by urinary obstruction, but overall quality of life appeared similar for both groups. There's no evidence that one group suffered more or less than the other.

My concern is that the findings of the first study are being misinterpreted by the public in part because the lay-press reports have been misleading.

Rick

[ September 16, 2002: Message edited by: rbochnermd ]</p>

alek0 · 09-16-2002, 05:37 PM

Reports in the media often do not reflect true content of medical articles. Or other scientific articles for that matter.

Which is only part of the problem. The other part of the problem are MDs who will still recommend surgery, the way there are MDs who recommend Lupron after laparoscopy for endometriosis even though it makes no difference in conception rates compared to laparaoscopy only, who do episiotomies to "prevent tearing" even though research has proven the opposite, who recommend HRT in spite of the risks and many studies showing that it doesn't work at all for prevention purposes it was recommended so much (heart disease etc.) Common medical practice often has no scientific basis and I would really like to know why.

As for objectivity of medical researchers, I suppose that depends on who funds the study.

Actually that article was a pleasant surprise. It is often a lot more difficult to publish negative finding, which is quite a bad thing. If you have results which show that something commonly used does not work, you should be able to publish a full paper on that, not just comments or letters to the editor.

I have said it before and I'll say it again. Publication in peer reviewed journal does not mean that the study in question is a quality work. There are lots of problems with peer review process, but that's the best thing we have

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09-15-2002, 09:17 PM	#2
Happy Wonderer Veteran Join Date: Jan 2002 Location: Washington, the least religious state Posts: 5,334	One thing they don't really seem to quantify in this study is the quality of life for the people with the surgery vs. those without. Assuming that the people without the surgery are likely to end up with full-blown prostrate cancer (and the study shows that surgery does decrease this risk), what do we know about the effects of suffering this cancer? If the untreated group suffers progressively more pain and loss of function over the five years, I'd argue that they were worse off than those who were treated but died of an unrelated sudden stroke five years later. On the other hand, if the treated group suffers from the effects of surgery for five years and the untreated group dies painlessly and suddenly, that would argue for no surgery. My point is that in order to get statistical meaningful results, medical studies have to have a definite effect to compare to the treatment. It is much more difficult to quantify quality of life, especially for the elderly population. I think that this can lead to suboptimal decisions. "The treatment keeps you alive, so it is good" -- aside from the fact that it will make you as sick as a dog for the rest of your life. Or in this case, the argument seems to be "the treatment cures the disease but you are so old you are going to die of something anyway, so why bother?" There is more to life than survival. In my case, I'd probably go for the treatment especially as I consider myself healthier than the average and less likely to die of clogged arteries and the like. (I hope that decision is a long way off...) HW

09-16-2002, 05:37 PM	#4
alek0 Senior Member Join Date: Feb 2002 Location: Hong Kong Posts: 640	Reports in the media often do not reflect true content of medical articles. Or other scientific articles for that matter. Which is only part of the problem. The other part of the problem are MDs who will still recommend surgery, the way there are MDs who recommend Lupron after laparoscopy for endometriosis even though it makes no difference in conception rates compared to laparaoscopy only, who do episiotomies to "prevent tearing" even though research has proven the opposite, who recommend HRT in spite of the risks and many studies showing that it doesn't work at all for prevention purposes it was recommended so much (heart disease etc.) Common medical practice often has no scientific basis and I would really like to know why. As for objectivity of medical researchers, I suppose that depends on who funds the study. Actually that article was a pleasant surprise. It is often a lot more difficult to publish negative finding, which is quite a bad thing. If you have results which show that something commonly used does not work, you should be able to publish a full paper on that, not just comments or letters to the editor. I have said it before and I'll say it again. Publication in peer reviewed journal does not mean that the study in question is a quality work. There are lots of problems with peer review process, but that's the best thing we have

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