High risk vs. aggressive cancer - Advanced Prostate...

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High risk vs. aggressive cancer

RugbyVLS profile image
47 Replies

I understand the definition of high-risk prostate cancer (Gleason, PSA and/or spread), but that doesn't necessarily seem to be the same thing as aggressive cancer. How can aggressiveness be determined for high risk, localized cancer? Thanks for any insight and information.

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RugbyVLS
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47 Replies
Tall_Allen profile image
Tall_Allen

"Aggressive" isn't a medicalese-defined word. "High-risk" for localized PCa means high risk of recurrence after treatment.

Granica4818 profile image
Granica4818 in reply to Tall_Allen

So then what exactly does the Gleason score mean? or your PSA? I thought the higher the Gleason the more aggressive, or am I wrong. And the Rising PSA?

Tall_Allen profile image
Tall_Allen in reply to Granica4818

Gleason score, PSA, and T stage define the NCCN risk level.

tango65 profile image
tango65

In general, an aggressive disease refers to an illness that progresses rapidly and has a tendency to spread or worsen.

I think that the "aggressiveness" of PC is related to the mutations present in the cancer. BRCA and other HRR mutations, PTEN loss, Pt53 and the RB1 mutation, make the cancer more aggressive meaning that It will be more difficult to treat and may progress quicker.

The combination of PTEN loss, Pt53 and RB1 makes the cancer to progress quickly with visceral mets and poor response to treatments.

If you had biopsies and or a prostatectomy you could request a test to evaluate these mutations, and also you may request the Decipher test which can evaluate the risk of the cancer to spread and metastasize.

positive-thinking profile image
positive-thinking in reply to tango65

BRCA2 makes the cancer progress quicker? BRCA2 is more difficult to Treat? I thought that if men with BRCA2 are responding to treatment it is no difference than men that are not bRCA2? Does this really make the disease even more aggressive and castrate resistant and no more treatments come quicker? I did not know this

tango65 profile image
tango65 in reply to positive-thinking

thelancet.com/journals/ebio...

positive-thinking profile image
positive-thinking in reply to tango65

My husband is BRCA2 but responding well to triple therapy , your saying he has a worse chance of survival? Worse than just the 9 gleason and bone mets at diagnosis? I thought that people with BRCA2 went for a long period on same treatments as people with out BRCA2 . At that point they have alternatives same as other people do when they become castrate resistant ?

hopeful1956 profile image
hopeful1956 in reply to positive-thinking

I'm glad your husband is responding well to treatment. My husband was diagnosed at 65, Aug. 2021. Also BRCA2, Gleason 7 (4+3). He's in a clinical study (Amplitude). Has Zoladex shot every 3 mths, Zytiga (Abiraterone) 1000mg, Prednisone 5mg, and hopefully is taking the Niraparib 200mg as opposed to a placebo. He is responding well so far. PSA 0.008. Hopefully they both have many years of survival.

positive-thinking profile image
positive-thinking in reply to hopeful1956

Thanks for the reply , may I ask why your husband is in a trial already so soon after being diagnosed. I just noticed most men are usually in a trial after years ? I'm so happy your husband is doing well . My husband is also getting Zoladex and nubeqa , I do notice most guys are usually on the Zytiga with prednisone and hope the ones my husband is on do well . I wish you the very best.

hopeful1956 profile image
hopeful1956 in reply to positive-thinking

He was diagnosed Aug 2021 and once genetic results came back, his medical oncologist found 2 clinical trials he might be interested in. He opted for the Amplitude study conducted at Sunnybrook. He started the trial Feb 2022. You can look into participating in a trial from the onset. He has not received chemo or radiation.

positive-thinking profile image
positive-thinking in reply to hopeful1956

Wish you the best , we were told we are too far from doing any trials as we live in the Yukon . No oncologists here either , the one we had direction on treatment has left and not replaced himself with another . Glad you are in good hands where you live

Ahk1 profile image
Ahk1 in reply to tango65

I have PTEN loss and my MO told me I have an aggressive cancer. so far, my cancer is responding to treatments and I am hormone sensitive on IADT. does that mean, soon, it will become resistant to treatment? Thanks tango

tango65 profile image
tango65 in reply to Ahk1

Cancers with that mutation are more aggressive than others. In a particular individual is impossible to know what it is going to happen.

My cancer responded to therapy for 21 years, despite having PTEN loss. It is progressing in its 22nd year after it acquired other mutations.

Meanwhile the cancer responds to medication enjoy your life as much as you can.

I wish you the best of luck.

Ahk1 profile image
Ahk1 in reply to tango65

You have PTEN loss too from the start?

tango65 profile image
tango65 in reply to Ahk1

Yes.

Tony666 profile image
Tony666

I am sure tall Allen is correct on official definitions. And yet in practice many people use aggressiveness and high risk (or very high risk) interchangeably. Why? Because it is likely (though not certain) that “high risk localized” pc is in fact not localized. the scans and sampling can’t see it, so they call it localized. But if you have Gleason 9, say, some cells may well have broken off and gone out of the prostate. That’s why you really need to treat “high risk localized” pc aggressively, as if it was not localized.

GAdrummer profile image
GAdrummer

Aggressiveness is measured by determining the doubling time of the PSA. There are sites online that calculate it using two dated PSA results. Results vary over time as the cancer responds to treatment or continues to mutate.

Jost-58 profile image
Jost-58 in reply to GAdrummer

where can I find a site which reports this?

GAdrummer profile image
GAdrummer in reply to Jost-58

mskcc.org/nomograms/prostat...

is one of several when you google "PSA doubling time calculator"

Low risk, non aggressive is >1 year; high risk, aggressive is <6 months. When a treatment fails, the PSADT can drop to 1 or 2 months. Time for the next treatment.

maley2711 profile image
maley2711

This Doc calls into question the entire way we rely on "early" detection to change the outcomes for whatever risk level of PCa is diagnosed....

youtube.com/watch?v=-lt7UO3...

I did this many moons ago, but this Doc's views prompted me to Look for some studies on the effectiveness of early detection and early treatment. Best I could find....mostly studies in Europe.....study results are mixed on benefit of "early" surgery or RT. One VA study does show better avoidance of metastatic PCa for the men who had more PSA testing.

I also noted that age-adjusted PCa mortality rate for US has decreased significantlyover the past years, but "experts" are not unanimous at all in their reasons for seeing this decreased PCa mortality.

This general topic was discussed at a German symposium in 2017, where Richard Ablin presents his doubts about using the PSA test as a early detection marker......somewhere past the 1 hr mark, he and other professionals go back and forth re the effectiveness of early treatment for reducing mortality. Ablin does commend the PCa practitioners for advising more men to choose AS.

youtube.com/watch?v=lTjs0K-...

If you look at the studies for men who were eventually diagnosed as high risk but chose watchful waiting evidently, even many of those high risk men survived 10-15 years.....should those survivors have their cancers included in the "aggressive" grouping?

I have found the few Docs who have discussed my PCa with me reluctant/unwilling to discuss numbers/probabilities re benefit vs detriment in accepting early "pre-metastatic" surgery, RT, etc.

]I will try again with a different Kaiser RO. Is destiny already set by the time PSA-detected PCa is treated? Seems quite possible...or not?If it is, then would we really expect the Uros and ROs to communicate that and thus reduce their income streams???? Just a question I see some other folks asking.

For me strictly, I'd say aggressive PCa is that for which early initial surgery or RT will most likely fail and metastasis has already been detected or likely to be detected with/without early treatment. But hey, what do I know!!! Just another lost soul!!

MrG68 profile image
MrG68 in reply to maley2711

Ablin was the guy who discovered psa. It's quite an interesting video actually - the claims are that your life expectancy won't improve and the treatments do harm to a significant amount of people.

I'm my opinion though I guess it's more do the treatments avert potential problems like bone metastasis and the pain that goes with, it or do you take the potential heart failure from the treatments and the side effects.

It's also worth considering that there's side effects from not doing anything. Not being able to pee can become quite serious amongst other things.

You're damned if you do, and damned if you don't.

GAdrummer profile image
GAdrummer in reply to maley2711

My dad died of PCA when treatments were few. My brother caught the PSA rise very early and was cured by the radioactive seed treatment. At that time it wasn't available in his area, so he moved in with us for the summer-long treatment. My husband's PCA wasn't discovered until the the horse was long gone, headed to the next county. We had no high expectation of cure and spent ten years on the treatment rollercoaster. But we got lucky finally, something else is going to kill him.

jfoesq profile image
jfoesq in reply to maley2711

If you believe or others believe that all, or even most, doctors put their income concerns ahead of patient care than I feel sorry for you. There is no doubt that unscrupulous people exist in all professions and businesses but to make a statement or ask a question like the one you presented is really disgusting Your own writing even contradicts this as you cite the doctor in the video who commends doctors for recommending more and more patients for active surveillance.

maley2711 profile image
maley2711 in reply to jfoesq

I didn't say I believe anything...where did I say that? Your attributing to me something not true is "disgusting" IMHO. I didn't contradict anything, because I never said what you claim I said. And yes, this question about Doc incentives is not an uncommon one among the public. It may be an unwarranted question, but it is out there I can assure you. And yes, I believe it is common that many Docs shirk the discussion of SEs.....just my personal experience admittedly.

jfoesq profile image
jfoesq in reply to maley2711

My apologies. I jumped too quickly when reading your question of whether we should expect doctors to inform us if “our destiny is set at time of diagnosis” which would then have an impact on our treatment (or lack thereof) WHICH WOULD IMPACT THEIR INCOMES. The answers is YES! We should expect doctors to inform us of that (if in fact at destinies were set at Dx- which for the vast majority of us is completely false as Study after study has shown the SOC to be effective at prolonging life and minimizing pain. )And, I strongly believe most doctors would inform us if they knew our “destiny” and that treatment would be ineffective. It’s unfortunate that the small number of people in various professions end up causing some of the public to denounce said profession in its entirety. I do my best not to even contemplate condemning an entire profession based upon the few bad actors in said profession and would hope all others would do the same.

maley2711 profile image
maley2711 in reply to jfoesq

Actually, i have found few if any randomized studies comparing initial surgery or RT to do nothing. My Docs certainly din't use any such statistics to try and convince me to proceed with treatment???

To be fair to the patient, I believe the patient deserves to be shown the proven benefit!!! If the proof is there????

Goes for any medical treatment...or alternative treatment, and not just for cancer. Once you are recurrent and/or metastatic, then you will start hearing numbers about benefit of drugs vs no drugs!!!

Justfor_ profile image
Justfor_

PSADT is a good indicator of aggressiveness. I am high risk, yet, with a PSADT of 9.5 months, sitting on the middle of intermediate aggressiveness (6-11 or by some 6-12).

tn12 profile image
tn12 in reply to Justfor_

Is it possible to be high risk but not aggressive?

RugbyVLS profile image
RugbyVLS in reply to tn12

Good question. It seems that the indicators for agressiveness are evident after treatment ( PSADT and spread),so if the treatment is successful even for high risk, it might not be considered aggressive.

tn12 profile image
tn12 in reply to RugbyVLS

Ok that makes sense, thanks. My husband post RP was GL 3+4 but T3b. PSA has been 0.02 for 24 months.

Justfor_ profile image
Justfor_ in reply to tn12

Looked a his bio figures. With a PSADT of one year, maybe a bit more, he is doing far better than the average pT3b survivor. Wishing you good luck.

Justfor_ profile image
Justfor_ in reply to tn12

Posible yes, probable no. Statistically, the post RP 5 year BCR-free incidence is somewhere around 20%, when the average of all the risk stratifications is above 60%.

MarkS profile image
MarkS

I really don't get why some think the PSA test is a "hoax". It seems invaluable to pick up prostate cancer before metastasis. I have high risk PC (4+5). PSMA PET scan shows no visible spread, but to be on the safe side I am having RT to the prostate, lymph nodes and prostate bed. With luck, that will cure me. If I hadn't had the PSA test, the first I would know about it would have been bone pain from mets with incurable cancer.

Don717 profile image
Don717 in reply to MarkS

I turned it off when he said, "Women have a prostate". Yeah, I know about the Skene gland and it's development being similar. But it's as much a prostate as a penis is a vagina. Clearly this guy is just trying to be controversial and sell books. Without finishing the video I suspect his point, if he has one, is over-treatment? I think the medical community is addressing that without down-playing the significance of an increased PSA and investigating as to why one has an elevated PSA.

MrG68 profile image
MrG68 in reply to MarkS

Personally I wouldn't have used the term hoax. I think Ablin et all are suggesting that the test and the resulting treatments Aren't used appropriately for screening.

Doesn't diagnose cancer.

Produces unreliable results.

Uses a threshold value of 4, which was made up.

Affects 1 in 1000 men but impacts a large subset of the male population.

I like to think of it as going fishing with a wide net for cod fish but pulling in everything and you don't get many cod.

The question that wasn't addressed is: what do you replace it with. Yes, 1 in 1000 will only benefit, but that's a jagged pill to swallow if you're that 1 person. Also, you may be that 1 person, but the test doesn't pick it up since some cancers have low psa.

I personally think a better approach is not to use a threshold value if 4 and record a time series to work out a perceived growth rate.

Is it perfect? No. Will it catch everyone? No. Will it trap false positives? Yes.

But it would give a better indication to how aggressive the issue can be. Using a threshold of 4, which is just made up and waiting until it breaches that level, just seems like the wrong approach to me.

skiingfiend profile image
skiingfiend

High risk is a statement about probability of future outcomes.

Aggressive is a statement about current behavior of cancer.

An aggressive cancer increases the probability of negative outcomes in a shorter time frame.

NanoMRI profile image
NanoMRI

Since my diagnosis nine years ago I have not focused so much on how to characterize/label my cancer. I focus on navigating all the disparities in diagnostic and treatment methods we face. I am post RP, salvage RT to prostate bed and salvage ePLND, with spread confirmed as far as the para-aortic lymph nodes.

Apisdorsata profile image
Apisdorsata

Good explanations above. Remember that Gleeson score is made by the pathologist who looks at it under the microscope. The two grades are based on morphology. This correlates quite well with risk of spread, growth rate and eventual outcome. But it's not perfect. Sometimes 3+3, usually a good prognosis behaves more "aggressively" and sometimes 4+5 doesn't turn out to be so serious as might be expected. That's why other factors such as genetics, and other pathology findings such as positive margins, seminal invasion, etc are important.

Also, while there is generally good agreement between pathologists, some are just better at Gleeson grading and evaluations. So second opinions are wise.

SteveTheJ profile image
SteveTheJ

When I was diagnosed I was told that Gleason 8 was aggressive. If the doctor used the wrong word, so be it. My cancer has been controlled well by ADT. Best of luck.

Hawk56 profile image
Hawk56

Well, the responses are generally in agreement.

When I was diagnosed, my urologist said to me when reviewing the TRUS biopsy which graded out at GS 4+5, "Kevin, that's a pretty aggressive cancer..." I was at the beginning of my ten plus year journey, so, pretty naive. Looking back though the lens of what I know now, and my clinical history, what he was saying was I was high risk with that GS. My PSA did not put me in the high risk category (2.8) nor did the MRI and CT which "showed" no involvement of lymph nodes, bones or organs (though we know now, those scans did not have the capability to locate any PCa outside the prostate. Still, that was the standard of care, biopsy, image, decide, treat...

So based on that clinical data, I decided on surgery (fast forward to today, with newer imaging, results and treatment decision may be different!). When reviewing the pathology report, my urologist again did not say I had aggressive cancer though the GS of 4+4 put me in high risk. But, he felt with the clear margins, no ECE or SV and only 10% involvement in the prostate, I would not have any future "recurrence."

Still, that GS 4+4 put me in the 30% chance of recurrence group, high risk...!?,

18 months later, with two consecutive increases of PSA, .2, then .3, now the clinical data starts to indicate aggressiveness since BCR was <3 years after surgery.

When SRT failed and my PSA continued to climb, the PSADT and PSAV were clinical data points indicate "aggressive" PCa.

In March 2023 when it came back, the PSADT and PSAV again indicated aggressiveness though not all agree about calculations using USPSA tests.

So my take is, given my clinical history, my PCa is high risk for recurrence and when it reoccurs, it is aggressive and requires aggressive treatment decisions.

I have read articles as others have pointed out about early versus delayed treatment and overall survival, time to onset of symptoms...I don't disagree, however, my clinical data doesn't support waiting, high risk and aggressive.

Kevin

Clinical history
PELHA profile image
PELHA

How often do you get a new Gleason score? Hubs was a 9 but now with treatment his PSA has dropped from 9.6 to 1.8 in a month. Do you stay at the more aggressive level score or is this correlated to your PSA?

GAdrummer profile image
GAdrummer in reply to PELHA

How often do you see your doctor? With a medical oncologist, PSA test each visit. Only time will tell. Your current treatment is working right now. Yay! But how long will you stay on this treatment? What happens when you stop this treatment? An aggressive cancer will mutate to survive. The ensuing PSA rise during treatment means it is time to try the next treatment. Descriptions of the treatment process range from "whack a mole" to "roller coaster ride". The treatment process selects for stronger, more aggressive mutations over time.

You and your husband are in for the long haul fighting for his life. Be sure to maintain contact with your friends, especially when you feel overwhelmed by the stress. I worked full time during the first nine years of my husband's treatments, but retired to take care of him when the chemo treatments severely impacted his QOL: brain fog so severe he couldn't pass the neuro exam, falling to his knees on the exam room floor. I had to take over the family finances since he couldn't write legible checks and couldn't remember to pay bills, shredded statements/notices, and was an easy mark for scammers. Since diagnosis in 2009, I have had to call 911 for trips to the ER five times. Some of those were very close calls. If you don't have a blood pressure cuff, invest in one. You have to stay healthy to protect him.

PELHA profile image
PELHA in reply to GAdrummer

Yes he checks blood pressure daily. And takes calcium since Mets are bone. Thanks for info on Gleason. We are in the early stages so he seems pretty good and quality of life has not diminished but yes I will have to be prepared for the future with this. Thanks!!

maley2711 profile image
maley2711 in reply to PELHA

you do not have a redo of your Gleason score. It is what it is....the potential for metastasis remains the same....eg much higher than an initial 4+3 biopsy. If you hubby had RP, they usual confirm, upgrade, or downgrade the Gleason at that point....I believe?

maley2711 profile image
maley2711 in reply to PELHA

He was diagnosed 4+5 . What treatments since then? I don't see anything in his bio.

PELHA profile image
PELHA in reply to maley2711

I have to do the bio for sure. First have to figure out how and where this is. Will work on it.

j-o-h-n profile image
j-o-h-n

When dating my ex-wife: High Risk.

Married her: Aggressive.

Divorced: Relieved.

Good Luck, Good Health and Good Humor.

j-o-h-n

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