Active surveillance and upgrading

April 28, 2010 ( Barcelona, Spain) — Men with seemingly low-risk prostate cancer who are considered candidates for an active surveillance strategy might want to consider robotic-assisted laparoscopic prostatectomy (RALP) instead, a team from Mount Sinai Medical Center in New York City reported here at the European Association of Urology 25th Annual Congress.

Active surveillance, otherwise known as watchful waiting, has been enjoying a surge in popularity as a management option for men with low-risk localized prostate cancer.

The new results are drawn from a trial that evaluated the final histopathologic and functional outcomes of a large cohort of men who qualified for active surveillance under conventional active surveillance criteria, but who opted instead for RALP.

The researchers found a 44% rate of upgrading of cancers. However, there was a low rate of upstaging, and a nerve-sparing procedure was performed in most patients with excellent potency and continence outcomes.

"The findings are extremely important," David Samadi, MD, chief of the Division of Robotics and Minimally Invasive Surgery, told Medscape Urology. "First, the 44% upgrading rate in men whom we thought had slow growing disease represents men who never should have been placed on active surveillance in the first place," he said. "Second, we demonstrated that we can eliminate the risk of missing an aggressive cancer by successfully treating these men with minimal compromise to their quality of life."

Recent studies have questioned the use of radical therapy for all patients with prostate cancer, especially those with low-risk disease, in favor of active surveillance, Dr. Samadi observed. At the same time, improvements in surgical and radiotherapy techniques and perioperative management have decreased the morbidity of prostate cancer treatments.

Although active surveillance has been shown to be a valid treatment option for patients with low-risk disease, clinically low-risk prostate cancer does not necessarily translate into indolent or insignificant disease on final pathology, he added. Given the difficulties of accurate preoperative staging and grading of prostate cancer, upgrading and upstaging are extremely common at the time of prostatectomy.

When discussing treatment options for men who are candidates for active surveillance, it is important to be able to provide solid data on outcomes, both histopathologic and functional, following prostatectomy. This study was designed to provide such data to patients deciding between RALP and active surveillance.

Dr. Samadi presented data on 368 men deemed candidates for active surveillance who were drawn from a "prospectively maintained" database of 1249 RALPs.

Men who were categorized as eligible for active surveillance had a prostate-specific antigen (PSA) below 10 ng/mL, a clinical stage of T2A or below, and a biopsy Gleason score of 6 or less in 1 or 2 cores, with less than 50% tumor volume in a single core.

The study found that, on final histopathology, 147 active surveillance candidates (40%) were upgraded from a Gleason 6 biopsy score to 3 + 4 = 7. Fifteen (4.1%) patients were upgraded to 4 + 3 = 7, and 1 patient was upgraded to Gleason 8 or higher.

Seventeen patients (4.6%) were upstaged to pT3 or pT4 disease, and 12 of these were also upgraded.

Bilateral nerve-sparing was performed in 97% of patients.

Follow-up of 221 patients at 12 months showed that 88% of men had recovered potency (meaning they were potent preoperatively and had a Sexual Health Inventory for Men score of 16), and 95% were continent (meaning they needed 0 or 1 security pad per day).

Biochemical recurrence, defined as a PSA of 0.2 ng/mL at least 6 weeks after prostatectomy, occurred in 1.6% of patients at a median follow-up of 13.9 months.

As for which men with prostate cancer should choose active surveillance over RALP, Dr. Samadi said: "I think that active surveillance is ideal for older men and those whose PSA doubling time and velocity are slow."

"This study is interesting and somewhat surprising," Carl A. Olsson, MD, John K. Lattimer Professor of Urology (emeritus) at Columbia University College of Physicians and Surgeons in New York City, told Medscape Urology. "What surprised me is the 44% rate of upgrading, which is substantially higher than the 10% to 20% rate reported in the studies I am familiar with."

Dr. Olsson, who is also chief medical officer at Integrated Medical Professionals, PLLC, in Melville, New York, noted that "it would be interesting to know who did the actual pathology reporting."

He added that if the data are true, "they would put a damper on any policy of active surveillance in patients presumed to be at low risk preoperatively."

Dr. Samadi and Dr. Olsson have disclosed no relevant financial relationships.

European Association of Urology (EAU) 25th Annual Congress: Abstract 578. Presented April 18, 2010.

When everybody piled on the "Prostate Snatchers" bandwagon, I KNEW they were buying into a very risky treatment protocol..

Stay tuned for the next chapter, "Surgeons Fight Back!"

An,  I am the 1 out of 4 that stayed a 6 in the August club.  I can tell you that AS was not even an option I considered after after PCa was found in the biopsy for the exact reason that the pre surgery staging was nothing more than an educated guess and I was not comfortable with that.  I will never regret making the decision to have surgery as I believe I made the right choice. 

Ed

el perro said...
By the same logic, one would expect recently reported AS studies (or any AS study) to have a similar percentage of understaged men among their participants. Yet there seems to be no greater risk (in the studies I've seen) for adverse outcomes in these men. My point is that some higher-risk men are unknowingly included in AS programs due to imperfect screening, but they still fare ok overall. Maybe they are the ones that show progression and end up getting treated after a year or two, but they don't seem to be experiencing recurrence at any increased rate over the folks receiving immediate treatment, at least in the short term. So then the argument is that they may experience more recurrence 10 years from now... Maybe that will be the case (who knows?), but personally I would take my chances that there are better treatments available in 10 years.

It's back to another panic thread here on AS. Just think if it wasn't for PSA testing the last few years the amount of men dying from PCa wouldn't have dropped so drastically like it DIDN'T. Meanwhile over treatment and men living with lower quality of life effects has sky rocketed. It's still true for most that more men will die with PCa than of it. As far as waiting for new treatments many are not 10 years away but here now or will be soon. Look at my sig for one.

This is another "glass half empty arguement". The purpose of AS is to identify the 30% that have been understaged or who have progressed so the 70% can remain untreated for as long as possible. Also all data consistantly shows that the outcome is the same for deferred treatments, which the study doesn't mention.
As others have mentioned all of the other studies at Toronto, Hopkins and UCSF have an understaging or progression rate in the 30% range.
As Tud mentioned, if Scardino, considered by many to be the best surgeon in the US, can get a trifecta, (potency, continance and cure,) only 64% of the time then the incontinance and potency numbers are indeed laughable. Numbers like these contribute to the over expectations of those recieving treatment.
Some patients that would never consider AS would gladly wait for a progression in the face of bad pathological results instead of considering any adjuvant treatments. I don't see how this differs from AS except that it entails much more risk.
JT

We are hearing the same arguments over an over, like a broken record. Clearly a controversial area. The last word on AS has yet to be written.

This is an important topic. I think many lurkers are struggling with this decision--"To AS or not to AS?", as well as secondary questions, like "How to AS? How much should AS cost? How long to AS? Who should AS?" etc., etc. Should there be a permanent thread that collects the best posts on this issue?

Question for John T: Winning the trifecta depends more on the horses than the bettors. If the "horses" are men with low grade, organ confined PCa, what percentages win the trifecta in the hands of your favorite surgeon?

To continue with my somewhat labored horse racing metaphor, when Secretariat won the triple crown, who deserves greater credit? The horse, or the jockey, Ron Turcotte? Obviously both have some role.

I don't believe that the state of the PCa wouldn't make a difference in surgical outcomes. If you've got a small tumor, the margins are likely to be negative. If the PCa is small and organ confined, the surgeon can feel more comfortable leaving the autonomic plexus that surround the prostate alone. So, if you are discussing the risks of surgery in AS candidates, you really should look at stats for this subgroup, not all comers.

An, at this point I guess it's clear that you don't feel AS is appropriate.  And, if you want to stick your head in the sand and believe that 9 out of 10 men have a satisfactory sex life one year after surgery feel free.  But please don't expect such out-of-the-mainstream statistics to go without a challenge as there are literally hundreds of reputable studies that show this is not true. Some of us place a very high value on quality of life, hence we choose AS when we meet those criteria or less-invasive-than-surgery treatments when we don't meet the criteria for AS.

As postop said, these are the same arguments over and over...I guess we all just have to pick our experts, do our own research and examine our own psychological makeup when making our decisions. 

Tudpock (Jim)

sad, but true, fairwind

An,
Intermediate and high grade cancers have a very high probability of progressing so waiting for them to progress is not a good stratagy. Low risk cancers have a high probability of not progressing; that's the major difference.
As soon a patients understand that there are three different distinct types of cancer and they all act differently then progress will be made. Treatment should be fited to the individual cancer you have. One size does not fit all. If you don't buy into this basic issue then you should get the most agressive treatment you can for all PC, and that is a combination of surgery, radiation and HT, as this gives the best probability of eradicating the cancer whatever the risk level. I don't see many patients taking this route.
You don't believe that progresson in low risk pc can be easily identified before it is too late. I am convinced that it can with a probability in the high 90% level which is the same cure level for any treatment of low risk PC.
The patients in the study you cited were only selected based on psa and gleason on biopsy. I have always said that a color doppler and a PCA3 test should be a part of the criteria along with psa density. I would never go on AS without this. I'm sure that the majority of intermediate risk patients in this study screened in this fashion would have been eliminated as low risk. Any tumor identified with CDU would have been biopsied and all tumors above G6 would have been identified. This is how you initially separate the low risk from the higher risk cancers. This greatlly increases the probability that you indeed have a low risk cancer and not a higher grade that was missed. I personally think that everyone should get a CDU and PCA3 before deciding on any treatment regardless of the initial risk catagory just because it gives you so much more information on which to make a more informed decision.

JT

Gleason 6 (and under) ...All the good things about PC apply to you..
Gleason 7 ..................... You are in the Twlight Zone...Stay on your toes..
Gleason 8 and up ......... Your life will never be the same and it may be somewhat
shorter than you had planned..Little of what you read about
PC applies to you....

PSA .5 to 2.0 .................Congratulations! You are "normal"! Now bend over...
PSA 2.0 to 5.0 .............. See "Twilight Zone"..(and bend over)
PSA 5.0 to 10.0 ............ Call your urologist tomorrow and inquire about a biopsy..

Please forgive me, I'm in a weird mood tonight...
=========================================================

You may have been in a weird mood, but you were right on target. You have a way of boiling complicated topics down to the bare essentials.

From many different perspectives, a high gleason is difficult to overcome isn't it?

kbota

you and fairwind  have a point. it's dreary sometimes watching people having these endless mind battles here, trying to prove and disprove details about the subject that in the end, will have no practical bearing to the average patient that is dx or already battling with PC. For most of us, we trust our doctors and specialists, they are the experts, not the patient, no matter how "informed" the patient is, or however clever the patient thinks they are by "googling" endless hours about things PC. (not at all saying knowledge or learning is bad). for some of us, learning about this cancer and how it effects us and our treatment choices is why we are here. for others, it seems at time that is some kind of mental game or challenge to see who gets the "I am the smartest" award.

almost reminds me of the" my weiner is bigger than your weiner" silly game that some play.

if the experts can't even agree on these fine points in these studies, leaves little room for a mere patient to do better.

david in sc

Post Edited (Purgatory) : 9/14/2010 11:27:19 AM (GMT-6)

It is sad to see that we continue, collectively, to be in the state of projecting questionable results on data with high variance onto outcomes for single individuals.  But that's the nature of statistical analysis, and its the best we can do.

In my case, overtreated?  Probably.  Quality of life impacted by treatment?  Definitely.  If we were talking 1 in 10,000, or even 1 in 1,000 statistics for negative outcomes, OK, there's an argument to be made.  Although many of those I consulted in the medical establishment told me my negative outcome chances were " really low", for me, 1 in 10 type chances simply don't cut it.

It seems certainly true, and I think most here would agree, that the majority of PCa's are slow growing and we are overtreating.  But, without good differential tests to segment the populations early enough to not place the fast growing sufferer's at significantly increased risk of negative outcome, we will continue to have to take potshots in what is, at best, a dim twighlight.