Understanding Mr Gleason

Is a Gleason 7 an untreated Gleason 6?

If left untreated some more, would it become a Gleason 8?

Or, is the Gleason designation simply describing the Agressiveness of the cancer? Would a 6 remain a 6 "forever"? In other words, once a given Gleason score begins to spread, would a "6" spread more slowly than an "8"?

Is this where AGE is important?

Paul

The AVERAGE prostate gland, when surgically removed because of a cancer diagnosis, usually harbors 7 distinct and separate tumors. These tumors can be of widely differing Gleason grades or they can all be the same grade. The 12 core biopsy seldom samples all the tumors present. For reasons yet unexplained, all the tumors seem to develop at around the same time.

If the cancer can't be controlled with the treatments and drugs available today, it keeps doubling in volume until it overwhelms the victim...At this point, if the tumor mass is examined, it can be difficult to determine exactly which organ it originated in, the cells have become so badly altered they become almost impossible to identify.

Also, the cores taken and examined at biopsy are considered representative so there may indeed be higher G mutants that were not caught in the needles.

If none of the cancer cells progressed to more mutated Gleason scores then the cancer wouldn't progress and none of us would have to worry about it. While G3's may just stay at home and reproduce locally, G4's can leave the nest and strike out on their own, G5's will certainly do that if given the chance.

Initially, as you were not born with prostate cancer, there were no G's in your prostate, so where did they come from? Yeah, from normal prostate gland cells that mutated for 1 reason or another. Mine got a dose or 2 of arsenic and/or lead which flipped some epigenetic 'switches' and changed them into cancer cells.

In 17000 surgeries at John Hopkins not one G6 has ever been discovered that has matastized. This does not mean that it never will, just that it is extremely rare and should not even be a consideration in decision making.
A G6 can still grow locally and invade nearby organs such as the bladder and rectem, but this takes decades.
Many experts believe that the Gleason grade is in the cancer's cell DNA and does not change over time. So a G6 will rarely turn into a higher grade and higher grades discovered are usually new tumors that grow beside existing tumors.

Post Edited (John T) : 10/25/2015 11:01:31 AM (GMT-6)

The best example of dedifferentiation comes from AS series in which men have to ultimately get some form of treatment for their cancers.

In the past we discussed if is it possible that in a slow growing cancer such as prostate cancer, poorly differentiated tumor cells are produced in short periods of time? Or is this a stepwise process by which normal cells dedifferentiate at a variable rate as driven by genetic changes that cause them to gain or lose chromosomes? In time do Gleason Scores increase as tumors dedifferentiate?

A report by Dr. Klotz seems to support that notion. It is true that the progression rate is variable and it can take many years to become lethal if ever, but the notion that GS6 is immovable and never or even seldom will progress to higher Gleason scores by dedifferentiation is negated by this report done at 6.4 years of followup. Dr. Klotz reported:

“593 of 862 patients in our cohort had at least one repeat biopsy. Median follow-up was 6.4 years (max. 20.2 years). The total number of biopsies ranged from 2 to 6. 20% of patients were intermediate risk, 0.3 % high risk, all others low risk. 31.2% of patients were upgraded during active surveillance. The proportion of patients upgraded increased with time, suggesting prostate cancer dedifferentiation occurred at a rate of 1.0%/year (95%CI -0.12 to 2.16%/year)”

“Conclusions: This is the largest re-biopsy cohort, with long-term follow-up, described to date, enabling the first estimates of prostate cancer dedifferentiation in patients on AS. Dedifferentiation rates appear higher in patients with intermediate risk prostate cancer compared with those who are low risk at baseline.”

Some 20 years ago Dr. Tribuikait et al demonstrated that fact by doing repeated fine needle biopsies during a 24 month period. He reported a 23% rate of dedifferentiation supporting the concept of a gradual dedifferentiation of prostate cancer. This is a caution notice for younger men with intermediate PCa risk disease considering AS.

RalphV

The very long term active surveillance trials get around the problem of "missed" higher grade tumors by using multiple biopsies. The odds of missing something higher grade goes down with the number of repeat biopsies, and also with saturation biopsies and mpMRI-targeted biopsies. Johns Hopkins was (in)famous for their annual biopsies on their AS program.

Researchers at Johns Hopkins used statistical models and included misclassification rates (the difference between biopsy GS and pathology GS among men who had surgery immediately following diagnosis) to estimate the amount of true grade progression. They found that up to 1 in 4 men had true grade progression in the first 10 years and the average time to true upgrading was about 6 years. Keep in mind that 80% of men in the JH AS program are "very low risk," and we might expect grade progression to occur at higher rates in men initially diagnosed with higher grades.

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

- Allen

Gemlin, to look at it the other way, the AS reports suggest that 1/4-1/3 of AS patients eventually will need aggressive treatment....and JH is saying that it's because of progression...and the numbers nicely dovetail.

AS is not an 'end game' for all patients who go on it.

Even at JH, with their stringent AS protocol, 43% were able to stay on it without treatment for 15 years so far, and the remaining 57% had treatment. 8% had treatment without any adverse indications, so that means 51% did not require treatment for progression for at least 15 years. 31% were grade-reclassified as of 15 years (only 6% to a high-risk grade, and only .2% to metastatic). Some at JH had treatment because of increased cancer volume and PSA density.

In the Klotz study, 52% remained untreated after 20 years on the program. They have less stringent criteria for grade progression (4+3) and PSADT (<3 yrs).

I'm not sure what you mean by gradual or sudden, but the point is that in almost all cases they identified the change and treated it in a timely fashion.

- Allen

My PSA went from less than 2 to just over 4 in just 4 years (from age 51 to 55).

On biopsy all the positive cores, 6 of 12 all on one side, all were G9.

As logoslidat speculated, it seems sometimes this thing just jumps ugly all at once. If mine progressed from some low grade to what was found at biopsy, it sure did it awfully fast. The good news is I don't have to worry much about the Gleason grade getting worse!

Aside from the gleason 8, you have a great pathology report. They specimen{the prostate, capsule and wide margins} means they found no cancer other than that , that was bagged and sent pathology. Fixate on what is really good about you results , so as to avoid joining a club within a club that that ends up living and dying with the disease rather from it. Recover, be healed and get on with life. fwiw! The biggest lie,myth, misunderstanding, how ever you want to put it, that has floated around this forum is the drivel that Gl 8's and above will "always" result in a BCR. pure balderdash!

I thought that both surgery and radiation cause serious side effects a lot of the time...earlier for surgery,later for radiation. Depends on what you call "serious" too. "Essentially continent" to me is a serioius side effect..emphasis on "essentially". Same goes for "minor radiation proctitis"...an oxymoron to my way of thinking. especially in conjunction with "minor rectal incontinence". There is no good treatment..not quite sure how anyone can say , in general terms, not mine, that surgery always causes serious side effects and radiation never does...surgery is a lot of cut and paste, stretching , stitching,...radiation is blasting it's way through healthy tissue to get there for any of the external beam modalities and radiation does not stop at the exact edge of the prostate..no matter how careful they are..even for HDBT and SBRT Close , but no cigar.

Jack,
Fair enough....yeah, I guess there are good treatments if it "cures" you...I guess I meant "nice" more than good.:)