More AS controversy.

A retrospective look at the patient database of Bill Catalona (he has done over 5000 surgeries over 30 years) at patients meeting the D'Amico criteria for active surveillance (AS) shows a noticeable risk, al biet small, that delaying therapy does in fact show increased of disease progression. Catalona, one of the most respected surgeons in the world, has long been in disagreement with the guidelines for AS. he spoke at the AUA conference last year stating that AS is an option but does not come without risk. On one side of this argument are well established oncologists who argue against over treatment and PSA testing, and on the other side are the other are also well established oncologists that are proponents of screening and concerns about under treatment and a revert back to 1990 prostate cancer mortality rates which were quite higher than they are today.

www.physiciansbriefing.com/Article.asp?Aid=653127

It has been my opinion as an PCa advocate that AS is quite safe for men that are at the median age (67 years old) or older that meet the NCCN guidelines for AS. But we are in fact seeing doctors going outside those guidelines and recommending AS for all patients that have a G6 and PSA under 10. I believe that age is a major factor when considering AS. The NCCN guidelines are quite clear that AS is an option when life expectancy is under ten years for low risk patients (or 20 years when the risk is very low). But when I see men that are in their 50's and 40's on this protocol I hope that they understand that the mortality statistics are completely unknown when they live to their 70's and 80's and we need more data. Until we have that data, the risk of going outside the NCCN guidelines isn't the patients doctors making these recommendations ~ it's their own...

Tony

I completely agree. As much as I would love AS to be an option for me, I know that age is a very significant factor in the treatment of this disease. The younger you are, the more important immediate treatment is warranted. AS is not a treatment.

Tony,
It all makes sense. I didn't have the option of AS because of my Gleason 8 but even if I had a Gleason 6 I would have opted for surgery.

I fully agree, Tony

In the ideal world the biopsy sample would provide an accurate snapshot of the amount of and grade of cancer in the prostate.

But in 30-40% of cases (depends whose stats you look at) the cancer gets upgraded to a Gleason 7 from a Gleason 6. People with anterior dominant prostate cancer are even less likely to have their trans-rectal biopsy sample match up to the reality of the cancer. Color dopplers and other scanning techniques picked up large cancers quite well but don't really pick up smaller regions of high grade cancer. If you wait for small regions of high grade cancer to become larger regions of high grade cancer the benefit of finding the cancer early is diluted for the younger patient.

A person diagnosed young (40s, 50s) needs to consider these factors. The side effects of the operation (if this is where they want to go) are much better if the patient is younger.

AS is a relatively easy option to recommend to someone who is 70+. The small risks of AS are magnified for someone in their 40s or 50s. There is a gray area in the 60s in my opinion where people have to consider their expected life span.

An

JohnT,
I am no longer surprised that conflicting data can tear studies into shreds? The fact is that both sides are not using the same criteria when selecting which retrospective data that they want to display and both are biased. Bruce Trock is a statistician at JHU. He is a specialist at applying formulas to the database they have already accumulated. Nothing wrong with this and in fact I find it fascinating. But these studies that JHU and Northwestern (and their Trock equivalent) assembled are inappropriate to use as law. I look at it like I look at CNN.com and Foxnews.com. These are both the idiots and in the middle of these partisan news agencies somewhere is truth. We do not have survival statistics on AS as presented by both sources and that's truly what we need. The only way is a registry that will take years to accumulate. What we need even more are direct head to head level 1 studies...

An,
Very thoughtful post. I don't disagree with anything you stated with one exceptionI might adjust. The 30-40% of cases where the Gleason changed after prostatectomy can go in many ways. I have seen G6 go to G9. I have also seen G9 drop to G8 or G7. But you are correct that 30-40% change in Gleason grade after a full evaluation of the complete prostate is done.

Tony

AS has to be both Active and involve Surveillance.
It is not a case of the uro saying that your problem is not that serious and that you should come back in a couple of years.
Thus you have to have a plan for regular, perhaps even frequent PSA tests DREs etc to help establish the speed of any changes (PSA velocity or PSA doubling time).
Yes PCa is bound to get worse over time, the question to be answered during AS is "how fast is it happening": a PSA that goes up from say 4.5 to 5.2 over three months will ring alarm bells whereas one that goes from 4.5 to 4.6 over a year may not. (My father-in-law has been on AS for nearly 15 years as his PSA has stayed very stable, this is good news for him as his general health is such that he is not well enough to undergo surgery etc.)

A doc's view about how and when to react to having Prostate Cancer has to be seen in the context of how they/you have to react to other cancers. Other cancers can get nasty very quickly, so you don't often get much time to think about what you want to do let alone decide to do nothing besdies monitor it.
With me, after telling me I had PCa my uro told me to go home and have a think about what I might want to do and then come back and see him in two weeks, and he said it wouldn't matter if I needed twice as long. But for other cancers it just isn't like that - a couple of examples:
A few years ago my Mum's neighbour had a bad back, she went to the doc and was diagnosed with lung cancer and was dead within two weeks.
A young friend of a friend was diagnosed with melanoma and the mets had killed her within 9 weeks of the diagnosis.

Yes PCa is cancer, but it comes with a different time line. And AS is only an option because of this. And remember that opting for AS has to involve the realisation that at some point the monitoring will detect a change that will call for decisions to be made about treating the cancer.

Edited (I forgot to sign!)
Alf

Post Edited (English Alf) : 5/27/2011 8:37:52 AM (GMT-6)

I told my local Uro I had decided to have surgery and not AS because of my relatively young age. His response was "A reasonable man would not make this decision". My decision was based on reading as much as I could on the subject as well as information from forums such as this one. I spoke to as many people as possible who had gone through various forms of treatment. As well, in my case a lump appeared where there was none the year before. Was that a slow growing cancer? My goal is to to live as long as I can with as few side effect as possible. A reasonable decision for me was remove the cancer.

When I asked for a referral to another city his response was "Ok, at least won't need to deal with any of the complications you will have". Among many other thoughts racing through my mind at the time, the most passive thing I could think of was to run as fast as I could out of his office!

I think AS is fine if you are able to live with the knowledge you have cancer in you and you feel confident that it will be dealt with appropriately in the future. Some people do not. I was one them.

A decision on treatment is not taken lightly and is very personal. Once a person has decided on a course of treatment, it is the right decision for him. Some doctors do not seem to get that!

Active surveillance should be the preferred option for men diagnosed with low-grade prostate cancer who currently qualify for this protocol. Avoiding early treatment will prevent unnecessary treatments and their side effects. This said, it is important to recognize that even early stages of prostate cancer, if given enough time, could progress to more aggressive forms and become more difficult to treat.

Conservative treatment of prostate cancer has a long natural history. This history was written years before the advent of the PSA era, and the best-documented details of that history exist in the data compiled by the Scandinavian cancer registries and the studies of those data.

What do we mean by conservative treatment? To all intents and purposes, conservative treatment of prostate cancer meant that nothing was done until a man showed clear symptoms of prostate cancer. If a man had no symptoms, nothing was done. When a man showed symptoms (urinary retention, bone pain, etc.), these symptoms would be treated (“palliated”) so that the patient would have the best possible quality of life, but treatment was not carried out with curative intent.

For the most part, between 1970 and 1990, this is how prostate cancer was treated in Scandinavia, where excellent long-term health records are available going back decades. By looking at what happened to these men with conservatively treated prostate cancer, we can understand how the disease progresses when it is effectively undisturbed (untreated) until late in its course.

So let’s look at the available data, complied over the years in seven major Scandinavian analyses:

In 1994, Grönberg et al. reported that patient age alone could be a significant prognostic factor in prostate cancer. They analyzed data from a large and unselected cohort of 6,890 prostate cancer patients diagnosed between 1971 and 1987 in northern Sweden. Tumor grade information showed that 26.4 percent of the patients had well-differentiated tumors (grade 1), 40.0 percent had moderately differentiated tumors (grade 2), and 17.7 percent had poorly differentiated tumors (grade 3). There were no data to suggest that tumors in younger patients are more aggressive per se. However, loss of life expectancy differed significantly among all age classes and in all three grades. In patients with grade 1 tumors the time lost due to prostate cancer ranged from 11.0 years in the youngest age group to 1.2 years in oldest age stratum, even though the relative survival was approximately 0.70 in all age classes.

In 1996, Adolfsson published data on 172 Swedish patients diagnosed with T1-3NxM0 prostate cancer. These patients were all diagnosed between 1978 and 1982 and followed for at least 10 years using a surveillance protocol with deferred treatment on symptomatic progression. The median age at diagnosis was 68 years. The disease-specific survival at 10 years was 80 percent for the total series, 84 percent for the subgroup with T1-2 tumors, and 92 percent for patients with T1-2 tumors diagnosed when the patients were less than 70 years of age. For the subgroup with T3 tumors, the disease-specific survival at 9 years was 70 percent. In all subgroups the competing mortality was higher than the prostate cancer mortality.

In 1997, Johansson et al. published the results of a population-based study of 642 patients in Orebro, Sweden, with prostate cancer of any stage. The patients were consecutively diagnosed between 1977 and 1984, had an average age of 72 years, and were followed until 1994. Prostate cancer accounted for 201 of all 541 deaths (37 percent). Among 300 patients initially diagnosed with localized disease (T0-2), 33 (11 percent) died of prostate cancer. The corrected 15-year survival rate of 81 percent among these 300 patients was similar in 223 patients who had deferred treatment and in 77 who received initial treatment. The corrected 15-year survival was 57 percent in 183 patients initially diagnosed with locally advanced cancer (T3-4) and 6 percent in the 159 patients who had distant metastases at the time of diagnosis.

Also in 1997, Grönberg et al. published data from a study population of 6,514 patients diagnosed with prostate cancer between 1971 and 1987 in northern Sweden. about 85 percent of these patients died during the follow-up period, and the prostate cancer-specific mortality was estimated to be 55 percent. Age at diagnosis was found to be a strong predictor of prostate cancer death. Patients diagnosed before the age of 60 had an 80 percent risk of dying of prostate cancer, whereas those over 80 years of age at diagnosis had less than a 50 percent risk of prostate cancer-related death.

In 1999, Adolfsson et al. published a report on a prospective study of long-term survival in 50 selected men with locally advanced, non-metastatic prostate cancer managed with deferred treatment. The men were treated if and when symptoms occurred or upon their request. All patients were followed until December 1994, and no patient was lost to follow-up. The median patient age at diagnosis was 71 years. All patients were followed for at least 144 months or died before then. Actual overall survival rates at 5, 10, and 12 years were 68, 34, and 26 percent; disease-specific survival rates were 90, 74, and 70 percent, respectively. A third of the patients had received no cancer-specific treatment at follow-up or before death.

In 2004, Johansson et al. published additional data on the 223 men from the original Orebro study (see above) who had received deferred treatment. By this time, this patient cohort had then been followed for an average observation period of 21 years. The patients who had had tumor progression were treated hormonally (either by orchiectomy or with estrogens) if they had symptoms. After complete follow-up, 39/223 patients (17 percent) experienced generalized disease. Most cancers had an indolent course during the first 10 to 15 years. However, further follow-up from 15 years (when 49 patients were still alive) to 20 years revealed a substantial decrease in cumulative progression-free survival (from 45.0 to 36.0 percent), survival without metastases (from 76.9 to 51.2 percent), and prostate cancer-specific survival (from 78.7 to 54.4 percent). The prostate cancer mortality rate increased from 15 per 1,000 person-years during the first 15 years to 44 per 1,000 person-years beyond 15 years of follow-up.

While there is considerable variation in the results of these seven studies, several things seem to be very clear:
· Early stage, low and intermediate grade disease can be treated successfully with conservative therapy in older men with at least 10 and perhaps 15 years of life expectancy.
· More aggressive prostate cancer results in a high rate of mortality when left untreated.
· Age is an important factor in decision-making.
· If early disease is diagnosed at a young age, there is a high risk of the patient dying from prostate cancer if treated conservatively.

There has been resistance to accept active surveillance in the urology practice, but the door has been opened for men to learn and recognize this possibility if their cases qualify. As survivors with knowledge we need to advocate and support this modality for the benefit of those that follow our footsteps.

RalphV

Yet again something to sign up for - will have to pass on that.

I wonder if more men die of PCa in Scandanavia because they don't die of something else first? Here in the states there seem to be things lining up to kill us, like trying to drive to the store.

i fully agree with you, Ralph

...but also delaying the side effects of treatments for years and improving ones quality of life...

I agree, and it seems to me like this would be even more important to the younger among us. It was for me.

GOP,
The point I was trying to make is that progression of untreated prostate cancer can affect the QOL of that patient. Progression can cause excessive blood clotting, bone pain, obstructive urination etc. To ignore that possibility because PCa is indolent and will seldom kill, is illusory...

JohnT,
I was not comparing patients from the PSA era to current patients. I was pointing to the potential progression of untreated PCa. The current view is that PCa is indolent and always progresses slowly. The data shows that in the absence of early detection, there is excessive death and loss of QOL with disease progression. I am not trying to undermine active surveillance. On the contrary it is a very viable option for those that have their disease early on. To ignore the potential of PCa to progress while untreated because it is believed to be indolent can be dangerous and it is definitely not representative of the natural history of the disease.

RalphV