Naive Question: Is This Statement Still True?

Yes, it is true.

The word we commonly use today to describe this is "multi-focal." This is common.

If they are independent in origin, we call that "multi-clonal." Also common.

It happens sometimes that a single biopsy core sample may hit two independent foci of disease, separated by benign tissue. Not real common, but it happens.

Interestingly, however, is the fact that despite the typical multi-focal and multi-clonal heterogeneity of primary prostate tumors, most distant metastases (even from different anatomic sites in the same patient) share the majority of genetic alterations, which suggests a monoclonal origin of lethal metastatic cells...the bad ones.

Twenty years after that article, this factor remains a critical issue for the potential of genetically targeted treatments.

Post Edited (JackH) : 10/25/2016 9:07:08 AM (GMT-6)

Fairwind said...
The average cancerous prostate gland removed by surgery contains 7 separate and distinct tumors...

That's old, old information from the pre-PSA or early PSA era, several decades ago. It was correct in a paper published in 1991.



Today the mean number of tumors per RP specimen has decreased significantly...along with tumor volume, Gleason grade and other severity factors. In one contemporary study (published 2011) of about 1,000 prostates at Baylor University co-authored by David Bostwick, multi-focal tumors were found in 78% of all patients (22% were uni-focal). The average number of distinct cancer foci amongst the multi-focal cases was 2.24.

Further detail: 22% were uni-focal, as previously mentioned. 42% had just 2 foci. An additional 28% had only 3 foci. The remaining 8% had 4 or more foci.

Post Edited (JackH) : 10/25/2016 12:12:12 PM (GMT-6)

TA

So what are the implications of that fact ( if any) in terms of efficacy of various treatment(s) and probability of mets and survival?

Bob

In >80% of cases, the index tumor (the largest) has the highest Gleason score.

It means that focal therapy will not be a permanent cure for most men.

It is very rare for the pathology Gleason score to exceed the biopsy Gleason score by 2 grades or more. When a GS 3+3 is upgraded, it is almost always to a GS 3+4; a GS 4+3 is rarely upgraded to more than a GS 4+4. Anything GS8 or higher is "high risk" and is treated with exactly the same therapy. So the only "risk," if there is one, is for those who are GS 4+3 on biopsy who are upgraded to GS 4+4 or higher. GS 4+3 is categorized as "unfavorable intermediate risk" and is usually treated with exactly the same therapies as "high risk" patients - brachy boost therapy, and, more recently with SBRT or HDR brachy monotherapies. Adjuvant hormone therapy is also often prescribed for anyone with GS 4+3 or higher too.

One of the reasons I like SBRT or HDR brachy is because the dose to the prostate is exactly the same, whether the patient is low risk or high risk. What changes is the treatment margin - it is expanded for high risk - that is a result of uncertainty in staging, rather than Gleason score.

As far as surgery goes, it is curative, no matter what the Gleason score is, as long as the cancer has not breached the prostate capsule. One can consult a nomogram to get a feel for the risk that it is not contained.

So there are uncertainties in true Gleason score, uncertainties in staging, and cancer volume. That is something we all live with. All we have to guide us are population statistics, which do not predict for the individual. The best we can do is understand the risk and make our treatment decisions based on the level of risk and side effects we are willing to live with.

Boon,
Unfortunately, there is a limit to diagnostic accuracy with current technology. There is nothing that can identify a cancerous focus of less than about 2 mm even if it is very high grade. The only way to get "a more thorough diagnosis" is to remove the prostate and examine it under a microscope. Unfortunately too, surgery, radiation and adjuvant hormone therapy are the only therapeutic tools we currently have for radical treatment.

What improvement would you expect to see if all men had a saturation biopsy? Most men do not miss the most aggressive tumor - it is by far the most common outcome (about 70% of the time). Most men treated for PC do achieve a lasting cure.

Caveat Emptor Newbies..

But what percentage of the 30% misses are the high risk G9s and G10s? Since they make up significantly less than 30% of cancers, one would assume that the missed high risk cancers are much less than 30%. So how many people are treated as intermediate risk when they are actually high risk? (Full disclosure: I don't know, but it must be a relatively small number.)

It would be great to have perfect diagnostic tools, but we don't. And you have to strike a balance between being aggressive enough to not miss things, while not over-treating and using a sledge hammer, when a scalpel will do. My two cents...

PS I did have a saturation biopsy. It did find high-risk cancer (G9), but the process wasn't pleasant...

Thanks, TA, for tracking down the study you referenced. Very useful. I was surprised that the mean number of cores taken for the "saturation" biopsy was ~22 cores -- and ~ 15 cores for the transrectal biopsy.

Although the mean number of cores taken in the approaches was quite close, TTB more accurately predicted clinical risk category than TRUSB. Imagine the difference if TTB was defined as 50 cores and above! (I had 85 cores taken in my saturation biopsy.)

Meanwhile, a urologist at MSKCC commented recently that, in his experience, most recurrences in PCa are a function of missing lesions in the imaging/biopsy steps.

He added that he has never been unable to remove all of a lesion when he knows that it exists and knows where it is.

Based on this view: that the most likely source of error is in the biopsy step, he requires at least some patients to have a second biopsy if they have had just an MRI-targeted biopsy. (This and the preceding two paragraphs are taken from comments yesterday on the Inspire website.)

Boon1 said...
(I had 85 cores taken in my saturation biopsy.)

85 prostate needle core samples!!! Holy cow…it’s a wonder you had any prostate left after that!

The AUA publishes a 2015 Prostate Biopsy White Paper in which they clarify that the CDR, the cancer detection rate, of the 18-core saturation biopsy only becomes significantly different than the standard 12-core when the prostate volume is greater than 55cc.

How big was your prostate to begin with?

TA said...
That comment from an MSKCC urologist (presumably a surgeon) makes no sense to me. He removes the entire prostate - what's the difference if he knows exactly where inside of the prostate the tumors are before he starts cutting? It sounds absurd to me to do another biopsy if he's going to cut anyway. Perhaps the person who related that misunderstood. I do think that frozen sections are a good idea to assure he got it all.

TA, your presumption, quite understandable, was wrong. He is doing primarily IRE right now, not surgery, at least according to the poster on Inspire.

Post Edited (Boon1) : 10/26/2016 2:58:16 PM (GMT-6)