Cancer survival benefit of radical prostatectomy? Once again, it depends....

[Guest guest]

More results from the series of papers from the randomized Scandinavian prostate cancer studies comparing results of surgery versus "conservative management" or "watchful waiting" (in other words no primary treatment, just pallative care as cancers progress).

Cheers!

Jon in Nevada

Individualized Estimation of the Benefit of Radical Prostatectomy from the Scandinavian Prostate Cancer Group Randomized TrialEuropean Urology In Press, Uncorrected Proof Accepted 5 April 2012. Available online 18 April 2012 Vickers/a, , , Caroline e/b, Gunnar Steineck/c, Hans-Olov Adami/d, Jan- Johansson/e, Bill-Axelson/f, Juni Palmgren/g, Hans Garmo/h, Lars Holmberg/ia Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USAb University of Washington, Pharmaceutical Outcomes Research and Policy Program, Seattle, WA, USAc Karolinska Institute, Stockholm, Swedend Harvard School of Public Health, Boston, MA, USAe Örebro University Hospital, Örebro, Swedenf University Hospital Uppsala, Uppsala, Swedeng, h King's College London School of Medicine, London, UK, and Regional Oncologic Centre Uppsala/Örebro, Uppsala, Swedeni King's College London School of Medicine, London, UK, and Regional Oncologic Centre Uppsala/Örebro, Uppsala, Sweden

AbstractBackground Although there is randomized evidence that radical prostatectomy improves survival, there are few data on how benefit varies by baseline risk.

Objective We aimed to create a statistical model to calculate the decrease in risk of death associated with surgery for an individual patient, using stage, grade, prostate-specific antigen, and age as predictors.

Design, setting, and participants A total of 695 men with T1 or T2 prostate cancer participated in the Scandinavian Prostate Cancer Group 4 trial (SPCG-4).

Intervention Patients in SPCG-4 were randomized to radical prostatectomy or conservative management.

Outcome measurements and statistical analysis Competing risk models were created separately for the radical prostatectomy and the watchful waiting group, with the difference between model predictions constituting the estimated benefit for an individual patient.

Results and limitations Individualized predictions of surgery benefit varied widely depending on age and tumor characteristics. At 65 yr of age, the absolute 10-yr risk reduction in prostate cancer mortality attributable to radical prostatectomy ranged from 4.5% to 17.2% for low- versus high-risk patients. Little expected benefit was associated with surgery much beyond age 70. Only about a quarter of men had an individualized benefit within even 50% of the mean. A limitation is that estimates from SPCG-4 have to be applied cautiously to contemporary patients.

Conclusions Our model suggests that it is hard to justify surgery in patients with Gleason 6, T1 disease or in those patients much above 70 yr of age. Conversely, surgery seems unequivocally of benefit for patients who have Gleason 8, or Gleason 7, stage T2. For patients with Gleason 6 T2 and Gleason 7 T1, treatment is more of a judgment call, depending on patient preference and other clinical findings, such as the number of positive biopsy cores and comorbidities.

[Guest guest]

Of interest would be some sort of analysis of various labs in terms of their

distribution of biopsy scores in terms of Gleason and stage rating. In other

words, all other things being equal do some labs tend to rate core samples more

aggressively than competitors which would drive the patient more towards active

treatment.

Since the drive to make medical practices develop business models versus service

models and prostate cancer diagnosis driving a strong revenue stream model,

especially as it applies to newer proton therapy development and surgical

treatments, there has to be a temptation to tend to the higher revenue and/or

intervention direction for any given provider.

We see this tendency in recommendations made by providers, eg surgery by

urologists, radiation by radiation oncologists, so it would be logical in a

business sense (revenue/income) to see it in a general sense. That is

particularly true given the data on mortality with or without treatment being

approximately insignificant overall.

One has to admit this would be interesting data, I would think.

Rich

Green Bay, WI

>

> More results from the series of papers from the randomized Scandinavian

prostate cancer studies comparing results of surgery versus " conservative

management " or " watchful waiting " (in other words no primary treatment, just

pallative care as cancers progress).

>

> Cheers!

> Jon in Nevada

>

> Individualized Estimation of the Benefit of Radical Prostatectomy from the

Scandinavian Prostate Cancer Group Randomized Trial

> European Urology In Press, Uncorrected Proof Accepted 5 April 2012. Available

online 18 April 2012

> Vickers/a, , , Caroline e/b, Gunnar Steineck/c, Hans-Olov

Adami/d, Jan- Johansson/e, Bill-Axelson/f, Juni Palmgren/g, Hans

Garmo/h, Lars Holmberg/i

> a Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering

Cancer Center, New York, NY, USA

> b University of Washington, Pharmaceutical Outcomes Research and Policy

Program, Seattle, WA, USA

> c Karolinska Institute, Stockholm, Sweden

> d Harvard School of Public Health, Boston, MA, USA

> e Örebro University Hospital, Örebro, Sweden

> f University Hospital Uppsala, Uppsala, Sweden

> g, h King's College London School of Medicine, London, UK, and Regional

Oncologic Centre Uppsala/Örebro, Uppsala, Sweden

> i King's College London School of Medicine, London, UK, and Regional Oncologic

Centre Uppsala/Örebro, Uppsala, Sweden

>

> Abstract

> Background Although there is randomized evidence that radical prostatectomy

improves survival, there are few data on how benefit varies by baseline risk.

>

> Objective We aimed to create a statistical model to calculate the decrease in

risk of death associated with surgery for an individual patient, using stage,

grade, prostate-specific antigen, and age as predictors.

>

> Design, setting, and participants A total of 695 men with T1 or T2 prostate

cancer participated in the Scandinavian Prostate Cancer Group 4 trial (SPCG-4).

>

> Intervention Patients in SPCG-4 were randomized to radical prostatectomy or

conservative management.

>

> Outcome measurements and statistical analysis Competing risk models were

created separately for the radical prostatectomy and the watchful waiting group,

with the difference between model predictions constituting the estimated benefit

for an individual patient.

>

> Results and limitations Individualized predictions of surgery benefit varied

widely depending on age and tumor characteristics. At 65 yr of age, the absolute

10-yr risk reduction in prostate cancer mortality attributable to radical

prostatectomy ranged from 4.5% to 17.2% for low- versus high-risk patients.

Little expected benefit was associated with surgery much beyond age 70. Only

about a quarter of men had an individualized benefit within even 50% of the

mean. A limitation is that estimates from SPCG-4 have to be applied cautiously

to contemporary patients.

>

> Conclusions Our model suggests that it is hard to justify surgery in patients

with Gleason 6, T1 disease or in those patients much above 70 yr of age.

Conversely, surgery seems unequivocally of benefit for patients who have Gleason

8, or Gleason 7, stage T2. For patients with Gleason 6 T2 and Gleason 7 T1,

treatment is more of a judgment call, depending on patient preference and other

clinical findings, such as the number of positive biopsy cores and

comorbidities.

>

[Guest guest]

Rich wrote:

....

> Since the drive to make medical practices develop business

> models versus service models and prostate cancer diagnosis

> driving a strong revenue stream model, especially as it applies

> to newer proton therapy development and surgical treatments,

> there has to be a temptation to tend to the higher revenue

> and/or intervention direction for any given provider.

>

> We see this tendency in recommendations made by providers, eg

> surgery by urologists, radiation by radiation oncologists, so

> it would be logical in a business sense (revenue/income) to see

> it in a general sense. That is particularly true given the data

> on mortality with or without treatment being approximately

> insignificant overall.

....

This is a very interesting question. If doctors pressure

pathology labs for higher Gleason scores there might also be

insurance companies and HMO's pushing for lower scores.

However, in the final analysis, I suspect the most important

pressure is from patients and their lawyers pushing for accurate

scores.

Imagine a patient who forgoes treatment because his pathology

report said 6. His PSA goes up. He finally gets and fails

treatment. Someone looks at the old biopsy slides and says, this

wasn't 3+3, it was 4+3. You should have had treatment two years

ago. The patient sues. And of course the same problem could

happen with inaccuracies on the other side.

If I were a pathologist, even apart from ethical considerations

(which I like to believe would be paramount), I'd want to get the

most accurate possible analysis in order to forestall someone

criticizing my work and/or suing me.

    Alan

[Guest guest]

It is always difficult to ascertain

precise motivation for any actions – if indeed there is any such motivation..

What we do know about Gleason Scoring and

Grading is that the process is subjective. The experience of the person doing

the grading is paramount in getting consistency, but even then the only

likelihood is that they will be consistent with their results, and this doesn’t

mean that they are directly comparable with any one else’s results. In my

early days on this path of mine I recall one of the well known pathologists ( I

can’t be certain which one, so I won’t mention names) joining a

discussion on the subject saying that, if a patient could tell him what GS

(Gleason Score) he wanted, the pathologist could direct him to the laboratory

most likely to give him that score.

If I can take an example from another

field, the color of diamonds has a considerable effect on their value. The ‘whiter’

the diamond, the higher the value. Most estimates of values have been made on

the basis of the valuer’s subjective view of the color – and there

are some very fine gradations – many more than the three Gleason Grades. Insurance

claims can get very heated as valuers disagree on the color of the stone!!

There are many studies that show that if

identical specimens are given to a range of pathologists, there will be no

absolute agreement on the grades and scores of the samples – at best

about 45% will agree. The aspect of agreement of results has improved a little

in the current era because the number of grades has been reduced from five (1

thru 5) to three (3 thru 5) giving a range of GS from 6 thru 10 (which

results in a mid-point of 8) where previously it was 2 thru 10, giving a mid

point of 6. with fewer choices, there is bound to be more concurrence.

I was alerted to the change in grading by

an article on the large European study where mention was made that the

definition of prostate cancer was to be standardized by al countries

contributing data and that they would in future follow what was referred to as

the US definition, which said that any focus with a grade below 3 would not be categorized

as prostate cancer. So what would have been PCa GS 5(3+2) in the past would now

not be categorized as such. There was an implication that such borderline cases

might be upgraded to GS 6(3+3) and I have often wondered if that is why there

has been a significant difference in the outcomes of the European and US

studies, with the European studies showing a greater benefit from early

treatment than the US

studies. Naturally, if you are going to load your data with lower grade

disease, you’ll get a better result.

Anyone interested in the basics of GS who

doesn’t have any idea of what we are talking about might like to go along

to http://www.yananow.org/StrangePlace/forest.html#gleason

whilst anyone interested to see the knock on effect – the so called

Gleason Migration - can go along to http://tinyurl.com/2jnpbu to read an interesting

piece on how Gleason Grades and Scores have increased over the years, despite

other data showing that more and more diagnoses are of early stage disease

where one would not normally expect to find higher Gleason Scores. That article

was written 6 years ago and to the best of my knowledge the migration

continues. There is no doubt in my mind that logically, improving results for

the disease may well be influenced to some extent by this process.

All the best

Prostate men need enlightening, not

frightening

Terry Herbert - diagnosed in 1996 and

still going strong

Read A Strange Place for unbiased information at http://www.yananow.org/StrangePlace/index.html

From: ProstateCancerSupport [mailto:ProstateCancerSupport ] On Behalf Of Alan Meyer

Sent: Monday, 23 April 2012 9:04

AM

To: ProstateCancerSupport

Subject: Re:

Re: Cancer survival benefit of radical prostatectomy?

Once again, " it depends " ....

Rich wrote:

....

> Since the drive to make medical practices develop business

> models versus service models and prostate cancer diagnosis

> driving a strong revenue stream model, especially as it applies

> to newer proton therapy development and surgical treatments,

> there has to be a temptation to tend to the higher revenue

> and/or intervention direction for any given provider.

>

> We see this tendency in recommendations made by providers, eg

> surgery by urologists, radiation by radiation oncologists, so

> it would be logical in a business sense (revenue/income) to see

> it in a general sense. That is particularly true given the data

> on mortality with or without treatment being approximately

> insignificant overall.

....

This is a very interesting question. If doctors pressure

pathology labs for higher Gleason scores there might also be

insurance companies and HMO's pushing for lower scores.

However, in the final analysis, I suspect the most important

pressure is from patients and their lawyers pushing for accurate

scores.

Imagine a patient who forgoes treatment because his pathology

report said 6. His PSA goes up. He finally gets and fails

treatment. Someone looks at the old biopsy slides and says, this

wasn't 3+3, it was 4+3. You should have had treatment two years

ago. The patient sues. And of course the same problem could

happen with inaccuracies on the other side.

If I were a pathologist, even apart from ethical considerations

(which I like to believe would be paramount), I'd want to get the

most accurate possible analysis in order to forestall someone

criticizing my work and/or suing me.

Alan

[Guest guest]

Charlie De wrote:

> I am going for a prostate biopsy in 10 days. My friend's

> brother is a pathologist and is willing to look at the slides.

> When I told the doctor of my plan, he changed the subject.

>

> How can I make sure the slides are sent to my pathologist?

Charlie,

I don't know the answer to your question, but I think that

getting a second opinion is a great idea. I had three different

pathologists look at my biopsy slides and got three different

evaluations - 3+3, 3+4, and 4+3 - the last one by a pathologist

at the National Cancer Institute.

I also suggest that you ask for a copy of the pathology report

itself, not just your urologist's summary of it, but the actual

report from the person who examined the slides. Keep a copy for

your records and also give a copy to the pathologist who is going

to look at the slides for you. The report may call things to his

attention that he otherwise would have missed, and he might see

things that the original pathologist missed and be able to

specifically say that he thinks the report is inaccurate here or

there.

Of course if the two pathologists disagree, you won't know for

sure which one is right, or even if both are wrong. However if

the second guy reads the first guy's report and still disagrees,

he had a little more to go on than the first guy did.

Let's hope that both of them have a good understanding of

prostate cancer. With 300+ kinds of cancer, only a subset of

pathologists are real experts at any one kind.

    Alan

[Guest guest]

The slides are your property and the doctor must give them to you. Go to the Malecare web site (Malecare.org) and read about how to get your slides and where you can send them for a second opinion. It is very nice that your friend's brother is willing to look at them. However, if he does not normally read a lot of prostate slides you will be better served sending them to one of the suggest experts on the page. T Nowak, M.A., M.S.W.Director of Advocacy & Advanced Prostate Cancer Programs

Charlie De wrote:

> I am going for a prostate biopsy in 10 days. My friend's

> brother is a pathologist and is willing to look at the slides.

> When I told the doctor of my plan, he changed the subject.

>

> How can I make sure the slides are sent to my pathologist?

Charlie,

I don't know the answer to your question, but I think that

getting a second opinion is a great idea. I had three different

pathologists look at my biopsy slides and got three different

evaluations - 3+3, 3+4, and 4+3 - the last one by a pathologist

at the National Cancer Institute.

I also suggest that you ask for a copy of the pathology report

itself, not just your urologist's summary of it, but the actual

report from the person who examined the slides. Keep a copy for

your records and also give a copy to the pathologist who is going

to look at the slides for you. The report may call things to his

attention that he otherwise would have missed, and he might see

things that the original pathologist missed and be able to

specifically say that he thinks the report is inaccurate here or

there.

Of course if the two pathologists disagree, you won't know for

sure which one is right, or even if both are wrong. However if

the second guy reads the first guy's report and still disagrees,

he had a little more to go on than the first guy did.

Let's hope that both of them have a good understanding of

prostate cancer. With 300+ kinds of cancer, only a subset of

pathologists are real experts at any one kind.

Alan