Molecular progression of Gleason 6

Thanks.

Good opportunity to reinforce the importance of understanding the AS Fundamentals, and in particular the importance of sticking with the monitoring program, AS Fundamental #4, and then #3 that some men will move on later. mpMRIs will continue to play a bigger role in AS monitoring techniques.


ACTIVE SURVEILLANCE FUNDAMENTAL #1: AS is only for well-selected men diagnosed with PC. This is why “Step #1” for newly diagnosed men is to understand your risk category (see “Newly diagnosed…” thread). AS is not for men with high risk cases. Intermediate risk…maybe. This category has been split into two groups: 4+3 unfavorable intermediate risk cases, and 3+4 favorable intermediate risk cases, with other case characteristics also weighing-in. A number of AS programs have been including favorable intermediate risk cases. Low risk cases are the obvious candidates, and Johns Hopkins has had strict guidelines (although they have relaxed their AS criteria a couple years ago).

AS FUNDAMENTAL #2: Despite the limitation of being "well-selected" in #1, above, a huge percentage of newly diagnosed men are suitable for Active Surveillance as a first-line management strategy. Some AS programs are more restrictive than others, and there is currently no universally accepted formal protocol for AS entry, monitoring, or exit. Clinicians individually tailor a program of care to each individual case but based on common foundations. Using contemporary data of newly diagnosed cases in the US, somewhere between 40% and 67% of new PC cases are likely eligible for Active Surveillance, based on more and less restrictive program criteria.

AS FUNDAMENTAL #3: Some men who originally qualify for AS end up moving onward at a later date to a deferred treatment if signs indicate degradation in case characteristics. These men with deferred treatment are also “AS success stories!” (Please study and understand this PC Infolink article if you are confused by that statement: prostatecancerinfolink.net/2010/10/19/understanding-your-clinicians-mindset-about-active-surveillance/) The program worked for them, too, by showing them if and when treatment was appropriate. Complementary research has demonstrated that men on AS who move to deferred treatments have essentially the same outcome as those who sought immediate treatment.

AS FUNDAMENTAL #4: Ongoing monitoring is important to the continued success of AS programs and men enrolled in AS programs. Annual PSA blood tests are the norm. In the past, on-going AS cases have follow-up biopsies (after the 2nd, confirmatory biopsy) on an every 18-24 month basis (typically), depending on the program. In the current decade, mp-MRIs have been found to be superior to the old standard ultrasonic-guided needle biopsy, and most AS programs now at least intersperse mp-MRIs with needle biopsies.

Many newcomers do not understand the very important Fundamentals of AS...and your link helps underscore the importance of highlighting the risks to many new AS patients if they do not adhere to AS Fundamental #4.

This information can be a powerful "service" to men. Just like we had many men "rushing" to an aggressive treatment in the "PSA era," I want to see us do better in the "post-PSA era" and not have men rush recklessly into some made-up version of AS. Let's keep finding opportunities to get the word out.

Your post helps.

Dan0-

Thanks for posting this. This adds to other studies demonstrating clonal progression over time. I've seen confusion about this on HW and elsewhere. I think the confusion comes from the studies that showed that metastases never occur when there is only GS 6. That is a very different thing from inferring that GS 6 never progress to higher grades that can later metastasize. This underscores the importance of continual monitoring and biopsies for men on AS and focal therapy.

In fact, I did an extensive post about this less than a month ago showing additional evidence. I'll quote it here to bolster your argument, and so people reading it won't just think it's an anomaly.

Allen said...
We know from Klotz's AS study that after 20 years of f/u (and we can be reasonably certain that higher grade cancers weren't missed in every biopsy over 20 years), about half of low risk tumors progressed to require treatment, and about half were indolent. This was affirmed by a JH study that found that "The estimated likelihood of grade progression within 10 years of study entry ranges from 12% to 24% depending on the prior."

onlinelibrary.wiley.com/doi/10.1002/sim.6003/abstract

And a study at Harvard found that some men originally biopsied as GS 6 did eventually die of PC:

Clinical predictors of survival in men with castration-resistant prostate cancer: Evidence That Gleason Score 6 Cancer Can Evolve to Lethal Disease

Were you referring to the following JH study? It found, as I said, that "Out of over 14,000 totally embedded RPs from multiple institutions, there was not a single case of a GS≤6 tumor with LN metastases." Which is different from saying that GS6 tumors never progress.

DO ADENOCARCINOMAS OF THE PROSTATE WITH GLEASON SCORE (GS) ≤6 HAVE THE POTENTIAL TO METASTASIZE TO LYMPH NODES?

This was corroborated in several studies:

Gleason 6 Prostate Tumors Diagnosed in the PSA Era Do Not Demonstrate the Capacity for Metastatic Spread at the Time of Radical Prostatectomy

Nationwide prevalence of lymph node metastases in Gleason score 3 + 3 = 6 prostate cancer.

Now, it may be that G4 and G3 progress from a common precursor, or they may progress from one to the other, or via both mechanisms. Either way, grade progression does occur which is why it's so important to have those repeat biopsies on active surveillance or focal therapy.

Clonal Progression of Prostate Cancers from Gleason Grade 3 to Grade 4

Tracking the clonal origin of lethal prostate cancer

www.healingwell.com/community/default.aspx?f=35&m=3642963

- Allen

Certainly a good addition to the research. It does point out the (somewhat obvious) need to keep an eye on things, even if the initial diagnosis is a solid G6. The understanding that "G6 never does anything" is not exactly correct--with potentially deadly consequences.

Thanks for the link.

halbert said...
Certainly a good addition to the research. It does point out the (somewhat obvious) need to keep an eye on things, even if the initial diagnosis is a solid G6. The understanding that "G6 never does anything" is not exactly correct--with potentially deadly consequences.

Thanks for the link.

Well put.

While G6 prostate cancer may not have ever killed anyone, it would be a word game to state that it has no credible potential to.

I believe we'll soon know the good guys from the bad guys.. One man's opinion.

Post Edited (island time) : 6/17/2016 9:16:39 PM (GMT-6)

Yeah, there's nothing which prevents the future development of higher grade cancer cells later. Just because you only have 3+3 now, or 3+4, when you go on AS you will need to monitor regularly to see if something more aggressive "pops up." Not necessarily frequently, but regularly. That's fundamental to AS.

halbert said "I agree with IT--and I've said this for a while now--the day is coming, and probably sooner than we know, when it will be possible to differentiate the indolent from the needs treatment at the time of diagnosis. And THAT will be a great day."

Indeed it will!