Multiparametric MRI (mpMRI) over diagnosis?

Posted by handera @handera, Dec 2, 2023

Due to an accelerating PSA (5.06 to 7.8 in 7 months) a MPMRI (multiparametric MRI) was ordered that indicated 3 lesions (PIRADS 3, 4 and 5 - one each). Fusion biopsy targeted the three lesions and 12 additional random cores obtained (21 cores total). Results indicated two of the lesions were Gleason 3 + 3, but the random cores found 2 additional cores with small percentages of Gleason 3 + 4. My question is whether it is typical for an MRI not to find the more aggressive cancer? Could it be due to the fact that the MRI machine was a 1.5T and not the more advanced 3.0T type? Or was it simply a misread MRI????

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@pablo81

Primary reason I have resisted is concern over spread if the lesion is cancer because of invasive nature of the biopsy.....

Literature says to monitor via another MRI in 2 years to check if growing. I had a second MRI at 13 months which showed no growth.

Also most recent PSA Free test suggests that "if" it is cancer it likely is not aggressive. Everything seems to be "if" or "maybe"..

Why was MRI ordered? Because I had a PSA of 4.3.... Later I learned that 4.3 is not high for my age.

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I agree. It’s been 7 weeks since my biopsy and I’m not yet 100% back with full sexual function. I was never told about this issue…I am a very healthy 67 year old, taking no medications, so there is no reason for this issue…except the fact that I had a biopsy.

I felt rushed into getting a biopsy because my mpMRI indicated there were PIRAD 4 and PIRAD 5 level lesions.

It turned out that all they found, in those targeted mpMRI lesion areas, were 3 + 3 Gleason cancer cells; which are known to NEVER metastasize.

I was one whose mpMRI was overdosed. Apparently that can happen as much as 75% of the time with those told they have a PIRAD 5 lesion (even from the very best radiological mpMRI reading laboratories), depending on the radiologist who reads your mpMRI scan, according to Dr. Matt Cooperberg (UCSF), a prostate cancer specialist.

My urologist could not answer this question, when I posed it afterwards…so I had to find the answer through my research.

I decided to go AS…and I will be very reluctant to undergo another biopsy, unless my PSA spikes through the roof AND I get 2nd and 3rd opinions on a subsequent mpMRI that CONFIRM lesions which are definitely PIRAD 5.

All that said, I have significantly changed my diet and increased my running to 10 miles per week.

I don’t expect any more problems with my PCa, based on everything I’ve studied about men who have received a similar PCa diagnosis AND have taken the subsequent actions that I have now implemented.

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Gentlemen: These are truly your choices and I respect them.
I had no problems with my transrectal biopsy.
My PSA was 3.9 in 2018 at age 68; 4.6 in 2020 at age 70 (some literature said age 70 normal PSA was less than 6); 5.9 in 2021 (retaken 3mos later 5.7).
Reluctantly (because I did not want to overreact) saw a Urologist in Dec 2021, who scheduled MRI for April 2022 and follow up for June 2022. No apparent urgency.
MRI identified PRads 4 & 3.
Fusion guided 18 core biopsy July 2022 found Gleason 8s and one 9.
Surgery August 2022. All clear postop, BUT extraprostatic extension (EPE) found outside prostate capsule, but within surgical boundaries.
Failed 1st postop PSA @ .19 ( repeated 30 days @ .18).
Now 1 year later, I have completed 2 mos of IMRT to the pelvic floor and pelvic lymph nodes, within a 4 mos course of ADT, and just received 1st post tx PSA < .02 (undetectable).
And I am very grateful for that uPSA result and all of my diagnoses and care.
However, I have some remorse about whether or not I could have, or should have, acted sooner vs not wanting to get caught in the Gerbil wheel of worrisome inconclusive diagnostic tests.
So, I get it and am only sharing my actual experience.
And I am not sure that I have ever seen a definitive medical statement that Gleason 3 + 3 never evolves to higher, more aggressive Gleason scores.
I only wish you and all the best, and that you never have to experience any progression or concern.
From my 2 yr journey, the only thing that is clear to me, is that nothing about this insidious disease is clear.

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@michaelcharles

Gentlemen: These are truly your choices and I respect them.
I had no problems with my transrectal biopsy.
My PSA was 3.9 in 2018 at age 68; 4.6 in 2020 at age 70 (some literature said age 70 normal PSA was less than 6); 5.9 in 2021 (retaken 3mos later 5.7).
Reluctantly (because I did not want to overreact) saw a Urologist in Dec 2021, who scheduled MRI for April 2022 and follow up for June 2022. No apparent urgency.
MRI identified PRads 4 & 3.
Fusion guided 18 core biopsy July 2022 found Gleason 8s and one 9.
Surgery August 2022. All clear postop, BUT extraprostatic extension (EPE) found outside prostate capsule, but within surgical boundaries.
Failed 1st postop PSA @ .19 ( repeated 30 days @ .18).
Now 1 year later, I have completed 2 mos of IMRT to the pelvic floor and pelvic lymph nodes, within a 4 mos course of ADT, and just received 1st post tx PSA < .02 (undetectable).
And I am very grateful for that uPSA result and all of my diagnoses and care.
However, I have some remorse about whether or not I could have, or should have, acted sooner vs not wanting to get caught in the Gerbil wheel of worrisome inconclusive diagnostic tests.
So, I get it and am only sharing my actual experience.
And I am not sure that I have ever seen a definitive medical statement that Gleason 3 + 3 never evolves to higher, more aggressive Gleason scores.
I only wish you and all the best, and that you never have to experience any progression or concern.
From my 2 yr journey, the only thing that is clear to me, is that nothing about this insidious disease is clear.

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Thanks for a thoughtful and detailed description of your experience!

PCa is a disease that is best understood to be a sliding scale of severity for the majority of older men.

This is due to the history of how it was originally defined and treated and what is now understood, in 2023, by specialists on the cutting edge of the field today.

My comment that 3+3 Gleason NEVER metastasizes is based on the latest work of Dr. Matt Cooperberg and his colleagues (there are others).

In fact, there is a serious debate to rename Gleason 6, see the following website to read both sides of the debate:

https://www.urotoday.com/conference-highlights/aua-2023/aua-2023-prostate-cancer/144054-aua-2023-debate-renaming-gleason-6-prostate-cancer.html

Excerpt below:

“On that note, Dr. Cooperberg took over and titled his talk “Its Time to Rename Gleason 6.”

Cancer (from the Latin) implies insidious growth and spread – and nomenclature matters.

In a recent paper and call to action by him and colleagues (Eggener et al. JCO 2022), they make the following key points:

- Gleason 6 is extremely prevalent. Diagnosis is often incidental to BPH and other factors related to BPH (ie elevated PSA, urology visits)

- Gleason 6 never metastasizes

- Gleason 6 has few, if any, molecular hallmarks of cancer

- AS is still done highly inconsistently

- “Gleason 6” as a non-cancer would still require surveillance

- The harm: benefit ratio of screening is improved the less we overdiagnose low-grade disease”

At the end of the day, every man facing the vagaries of PCa, needs to be satisfied (and hopefully thankful) for whatever plan or treatment they decide upon with their doctor(s).

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@handera

Thanks for a thoughtful and detailed description of your experience!

PCa is a disease that is best understood to be a sliding scale of severity for the majority of older men.

This is due to the history of how it was originally defined and treated and what is now understood, in 2023, by specialists on the cutting edge of the field today.

My comment that 3+3 Gleason NEVER metastasizes is based on the latest work of Dr. Matt Cooperberg and his colleagues (there are others).

In fact, there is a serious debate to rename Gleason 6, see the following website to read both sides of the debate:

https://www.urotoday.com/conference-highlights/aua-2023/aua-2023-prostate-cancer/144054-aua-2023-debate-renaming-gleason-6-prostate-cancer.html

Excerpt below:

“On that note, Dr. Cooperberg took over and titled his talk “Its Time to Rename Gleason 6.”

Cancer (from the Latin) implies insidious growth and spread – and nomenclature matters.

In a recent paper and call to action by him and colleagues (Eggener et al. JCO 2022), they make the following key points:

- Gleason 6 is extremely prevalent. Diagnosis is often incidental to BPH and other factors related to BPH (ie elevated PSA, urology visits)

- Gleason 6 never metastasizes

- Gleason 6 has few, if any, molecular hallmarks of cancer

- AS is still done highly inconsistently

- “Gleason 6” as a non-cancer would still require surveillance

- The harm: benefit ratio of screening is improved the less we overdiagnose low-grade disease”

At the end of the day, every man facing the vagaries of PCa, needs to be satisfied (and hopefully thankful) for whatever plan or treatment they decide upon with their doctor(s).

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"Gleason 6" never metastasizes." But Gleason 6 at one point sometimes later is Gleason 7=4+3 (4 is more prevalent than 3 in the biopsy.) And Gleason 7=4+3 can actually be 4+3+5 (the score is the two most prevalent types of cells in each biopsy.) And when my prostate was removed, there was one small spot with negative margins (the cancer[-ish, if you feel like Cooperberg] cells extended to the edge of what was reviewed by the pathologist after the surgery. And yes, in that case, there is a 50-75% likelihood the cancerous "prostatic" cells prosper to the point of being identifiable outside the prostate itself. (Metastasis is defined as secondary malignant growths at a distance from the primary site, not adjacent to it.)
So yes, I can agree that Gleason 6 "never" metastasizes--by definition. So if you want to call it something other than cancer, that's fine with me.
I began "active surveillance" in my early 40s. However, 20 years and some major relocations later, that surveillance was not only less active, it became inactive. (I didn't know the standard medical screening guidelines had changed and my then primary MD did not know or discuss my relevant history, she just didn't order the screening with my bloodwork.) When that changed and I had a better MD, behold, a lot more PSA for my somewhat enlarged gland and with an mpMRI, behold, a nodule of concern. But then the next mpMRI, behold, a second nodule of greater concern (2 months apart, so probably a difference in data and/or interpretation, not growth.) And then the mpMRI guided transperineal biopsy, behold, intermediate unfavorable (7=4+3), only in the nodule not discovered on the first mpMRI.
So that is my story of how I went from "this is overblown" to Stage 2 (where Stage 4 is metastasis.) Of course, I would still like to stop where I am, but my active surveillance post-RALP is a lot more active now than it was a few years ago :-).

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@spino

"Gleason 6" never metastasizes." But Gleason 6 at one point sometimes later is Gleason 7=4+3 (4 is more prevalent than 3 in the biopsy.) And Gleason 7=4+3 can actually be 4+3+5 (the score is the two most prevalent types of cells in each biopsy.) And when my prostate was removed, there was one small spot with negative margins (the cancer[-ish, if you feel like Cooperberg] cells extended to the edge of what was reviewed by the pathologist after the surgery. And yes, in that case, there is a 50-75% likelihood the cancerous "prostatic" cells prosper to the point of being identifiable outside the prostate itself. (Metastasis is defined as secondary malignant growths at a distance from the primary site, not adjacent to it.)
So yes, I can agree that Gleason 6 "never" metastasizes--by definition. So if you want to call it something other than cancer, that's fine with me.
I began "active surveillance" in my early 40s. However, 20 years and some major relocations later, that surveillance was not only less active, it became inactive. (I didn't know the standard medical screening guidelines had changed and my then primary MD did not know or discuss my relevant history, she just didn't order the screening with my bloodwork.) When that changed and I had a better MD, behold, a lot more PSA for my somewhat enlarged gland and with an mpMRI, behold, a nodule of concern. But then the next mpMRI, behold, a second nodule of greater concern (2 months apart, so probably a difference in data and/or interpretation, not growth.) And then the mpMRI guided transperineal biopsy, behold, intermediate unfavorable (7=4+3), only in the nodule not discovered on the first mpMRI.
So that is my story of how I went from "this is overblown" to Stage 2 (where Stage 4 is metastasis.) Of course, I would still like to stop where I am, but my active surveillance post-RALP is a lot more active now than it was a few years ago :-).

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Thank you for relating your AS experience.

What was your Gleason score when you started AS in your early 40’s?

I’m also curious as to how you made that initial AS decision versus selecting some kind of treatment.

It is my understanding that the PCa community was much more reluctant to recommend AS twenty years ago.

I have a friend who was diagnosed with Gleason 6 twenty years ago and went with RP. He is now in his early 70’s and doing fine.

I think the most important decision any man diagnosed with PCa, no matter what plan or treatment he ultimately chooses, is what he plans to do about his WEIGHT, his DIET and his level of vigorous AEROBIC exercise. These last three items are totally within the control of the individual.

How we got ourselves into a position where PCa is diagnosed is history.

Once the stage of one’s PCa is absolutely confirmed (no small matter, btw); then IMHO the most important decision is what one plans to do about their Weight, Diet and Exercise.

This decision should be made BEFORE considering the AS, surgery, radiation and/or ADT options.

Again, from my research the former decision will guide the later.

IMHO the less one plans (and commits to do) to change their weight, diet and level of exercise, the more radical the level of treatment selected should be, with the full acceptance of the higher risks of the negative side effects that come with ALL forms of treatment.

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PSA 12 had eligard 6month injection 7/3 starting 5 day radiation treatment 12/18

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@handera

Thank you for relating your AS experience.

What was your Gleason score when you started AS in your early 40’s?

I’m also curious as to how you made that initial AS decision versus selecting some kind of treatment.

It is my understanding that the PCa community was much more reluctant to recommend AS twenty years ago.

I have a friend who was diagnosed with Gleason 6 twenty years ago and went with RP. He is now in his early 70’s and doing fine.

I think the most important decision any man diagnosed with PCa, no matter what plan or treatment he ultimately chooses, is what he plans to do about his WEIGHT, his DIET and his level of vigorous AEROBIC exercise. These last three items are totally within the control of the individual.

How we got ourselves into a position where PCa is diagnosed is history.

Once the stage of one’s PCa is absolutely confirmed (no small matter, btw); then IMHO the most important decision is what one plans to do about their Weight, Diet and Exercise.

This decision should be made BEFORE considering the AS, surgery, radiation and/or ADT options.

Again, from my research the former decision will guide the later.

IMHO the less one plans (and commits to do) to change their weight, diet and level of exercise, the more radical the level of treatment selected should be, with the full acceptance of the higher risks of the negative side effects that come with ALL forms of treatment.

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1) In my 40s I had PSA's in the 4's and was not referred for biopsy by the urologist--just digital rectal exams and PSA's back then. 25 years ago there were less tools. At first he monitored PSA yearly, then tapered off after several years without progression. No one had advised me not to bike and I was biking quite a lot starting sometime around then.
2) My uncle 12 years older was a pioneer in exploring alternative treatments, near Stanford, CA, and followed at UCSF hospital. He oriented me to the options. The literature was also much spottier and less accessible back then. The support group he was a part of was face to face. He traveled an hour or two to get to the meetings.
3) In a broad sense, active surveillance has been around forever. Any time you are not taking medical action but monitoring concerns about PC in my mind is active surveillance, before or after RALP, radiation, ADT, or whatever. It used to be called watchful waiting, but the term was modified to emphasize that this was itself an active choice, not just a passive numbing. My active surveillance though over the years without progression of the PSA became passive. I did not become more active even when my cousin on the same side, two years older, was diagnosed and had RP. He has been very disappointed in his treatment plan, btw.
Question back at you: While I know that weight control, healthy eating and vigorous exercise are all good things, I am unaware of how that might impact PC. Can you point me to any research or evidence-based care standards in this regard? What has influenced you in this direction?

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@ spino:

Thanks for explaining your early AS experience…it must have been difficult to manage AS 25 years ago.

The problem, in 2023, is virtually the opposite…now one must filter through an enormous amount of “informational noise”.

I’m early in my AS research and experience, but it hasn’t stopped me from implementing what I know.

A couple clinical studies, for which I’m aware, are mixed. The MEAL study (January 2020) and “A Healthy Lifestyle in Men at Increased Genetic Risk for Prostate Cancer“ (May 2022). I continue to search.

Weight loss, diet modification and increased exercise to prevent or reverse GG1/GG2 are not prescriptive; however, this is one “treatment” that does not require a doctor’s intervention and ALL the “side-effects” are beneficial!

I have implemented a plan that brings my diet, exercise and weight loss goals together in a way, I believe, is synergistically and holistically greater than the sum of its parts.

I won’t spell out all the detail, but here’s an outline:

- increase daily water consumption to 1 gallon
- drink matcha tea rather than coffee
- incorporate intermittent fasting by skipping breakfast- until reaching weight goal
- focus on whole fruits and vegetables
- minimize supplements
- incorporate enough plant based protein
- eliminate processed meats, red meat, fried foods, eggs, cheese, soda, beer, milk, candy and ice-cream
- maximize high antioxidant/anti-inflammatory foods
- ensure diet enjoyment by finding acceptable substitutes
- increase vigorous exercise to a minimum of 45 - 60 minutes every other day
- ensure weight loss to a BMI of 22 and then maintain.

So far, I’ve reduced my BMI from 26 to 24, increased my running to 10 miles/week and enjoy everything in my new diet.

Regarding medical, I’m awaiting a biopsy 2nd opinion, a Decipher score and my first PSA, post biopsy.

I’ll modify my plan as I learn more about AS and get confirmation and more detail regarding my diagnosis.

Meanwhile, I’ve observed the following “side-effects” of my treatment plan:

- my cholesterol level (129) and Cholesterol/HDL ratio (3.8) have dropped to their lowest levels since I started measuring 40 years ago and I have stopped taking my 10mg statin, which I’ve been on for over 10 years.

- my shoulder joint inflammation pain has vanished.

- I no longer need my CPAP machine for good nights sleep, which I’ve used every night since 2006.

Of course, none of this means I’ll see lower PSA results and/or a slowing of the progression of my PCa. I leave that in the Hands of my Lord Jesus.

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handera,
two things can enhance your decision. First is the PSMA you might ask for the latest contrast Pylarify said to be better than gallium ga68. The very important second is somatic testing of the tumor (genetic testing of the tumor itself). Both will give clues about the aggressiveness of your cancer and about whether your cancer is likely to metastasize.
Prostate cancer treatment is making some interesting advancements. Pubmed the NIH and videos from your cancer treatment center (if you check the dates of publication) will give you more current information than books.
Best wishes

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@gently

handera,
two things can enhance your decision. First is the PSMA you might ask for the latest contrast Pylarify said to be better than gallium ga68. The very important second is somatic testing of the tumor (genetic testing of the tumor itself). Both will give clues about the aggressiveness of your cancer and about whether your cancer is likely to metastasize.
Prostate cancer treatment is making some interesting advancements. Pubmed the NIH and videos from your cancer treatment center (if you check the dates of publication) will give you more current information than books.
Best wishes

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Thanks for this useful information, I will certainly follow up.

It seems technology is moving so quickly in all fields of science, that books can seem like “yesterday’s news”.

IMHO, well documented, published books are helpful from the POV that a fuller analysis, having reasoned and well thought out arguments, can be made with the knowledge available at the time of writing…even in scientific fields.

Sometimes new findings need confirmation and can end up being refuted.

Regarding PMSA PET-CT for prostate cancer, my doctor indicated he does not recommend that scan for someone diagnosed with my stage of PCa.

For what it’s worth PMSA PET-CT apparently exposes one to 8.4 mSv of radiation; which is significantly less than standard PET scans.

https://www.esmo.org/oncology-news/psma-pet-ct-is-a-suitable-replacement-for-conventional-imaging-in-high-risk-localised-prostate-cancer

For comparison purposes, a chest x-ray is 0.02 mSv and a transatlantic flight is 0.1 mSv.

Of course, from what I’ve read, PMSA PET-CT is extremely precise and appears to provide some of the most convincing evidence of prostate cancer spread.

I would not hesitate to get one if my doctor believed there was a significant possibility to expect my cancer to have spread.

All the best.

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