Does lower grade prostate cancer evolve to more aggressive cancer?

@dan06 It's certainly quite possible that a low grade cancer with a limited number of mutations can accumulate additional mutations and evolve into a more aggressive species. This paper might be of interest
https://www.nature.com/articles/s41467-020-18843-5

Of course it can - that is the whole point of doing repeated biopsies. That is how cancer becomes more and more advanced and more and more aggressive. Even benign tissue that is left after focal therapy or RP can become cancerous over time.

All changes start with gleson 6 and over time further mutations happen and accumulate changing cells more and more. Over years they become gleason 7 than 8 etc.

NOW - not all mutations are the same ! For most people even though gleason changes, mutations are not making it super aggressive, just "little bit more" aggressive.
For some people though mutations that happen over time are numerous and VERY aggressive in nature.

What mutations make cancer cell aggressive ? Those that effect DNA fragments that control cell growth, cell death and cell autophagy. DNA stops regulating those very important process in cells and cells grow and divide exponentially fast and do not die ! They start looking strange, immature, loose some abilities while developing new ones and start detaching and making metastasis - they go rouge.

So - gleason 9 just does not happen all of the sudden - it starts as 6 and for some people stays 6 , for some not.

@surftohealth88

Well said. Thank you. I was trying to figure out how to convey what you were able to do so well.

I think the understanding that a Gleason 3+3 will not metastasize, has been mis-translated to it will not progress to a Gleason 7 or worse.

On a Ancan webinar, this question was asked. The Doctor answered just like you. Gleason 7 doesn’t start as a 7. It progressed over time.

In my intense studies over the past year, I have felt the information should be stated more deliberately: As long as cancer remains a Gleason 3+3, it should not metastasize. Over time, it may develop into Gleason 7 or higher.

Some of the multiple possibilities as we analyze our information. If biopsy indicates Gleason6:

-We may only have Gleason6
-We may have higher grade that was not sampled
-Over time, our true Gleason6 may progress to Gleason7 or higher.

Best Wishes to all.

@dan06 It is both new mutations either de-novo or type 6 cells and missed lesions since a random biopsy misses 99% of the prostate. An MRI followed by fusion biopsy gives a higher probability of sampling existing lesions, but even this will miss many. Progression from 3+4 to 4+3 can occur without new mutations. A 4+3 is when 50%+ are type 4 cells. Since 4 cells are more aggressive the percentage increases as they divide faster than type 3 cells.

Hello all. My 94 year old husband died this year from stage 4 prostate cancer. All I can say is it was a horrible death. I know because I stayed with him for months prior to his death. His doctor prescribed two different medications still in clinical trials. I know he wanted to die and he did. My understanding about mayoclinic/connect was no medical info. That we would support each other. Indeed, I received support before he died and in my still ongoing grief. We were married 42 years.

Perhaps all these comments are from prostate cancer specialists. Peace to all.

Although I don't know the answer one thing that hasn't come up is that pathology grading differs HUGELY. For me it sure has. I am sure there are plenty of people that didn't get that, but I am truly everywhere on the same pathology samples. So to be honest grading is not the best.

The one real person I trusted a lot was Dr Epstein
https://advanceduropathology.com/about-dr-epstein/
he had a real good thing going and good training going for his pathology students, but was let go by Hopkins so not sure his expertise will continue or not and I do NOT trust Hopkins now.

Anyway the same samples for me are all over on 3's and 4's and one place will call one sample a 3+3, another place 3+4, another 4+3 all on same exact sample. Another sample in the same biopsy just the opposite. Just truly all over, and many places re-did my pathology without my asking so I just watched it happen.

Obviously good image processing (the real name before everything was just called "AI") could add to consistency.

Another good thing that could happen is take all the lawsuits out of medicine. Pathologists are always thrown into all the lawsuits, just turn on TV ("my husband died of PCa, I got 10 million"). Doctors should not be facing this and what can pathologists do but pad on the over grading side.

@surftohealth88 Thanks for the response. After reading thru the responses and doing further research, IMO agree - GG1 can mutate to more aggressive cancer. Its also possible that it stays a GG1 for the remainder of your life. It is also possible that since a biopsy only hits about 1 percent of the prostate, it missed something and a higher grade cancer was present all along with the GG1. It is logical to presume all cancer starts out in a less aggressive form, but some appear to be biologically aggressive from relatively early in their development and may be diagnosed as Grade Group 4 or 5 without there having been a detectable Grade Group 1 stage beforehand. A cancer found as Gleason 9 (Grade Group 5) therefore does not necessarily mean it started as Gleason 6 and then progressed.

@jim18

The opposite is also true. My biopsy found 3+3 and 3+4 on the opposite side of the prostate that had a lesion that 2 different pathologists didn't see on the MRI (one said Pirads4, the second at Johns Hopkins upgraded to Pirads 4/5).

I don't know if this means that the biopsy found cancer was missed on the MRI or if this cancer developed in the 4 months between MRI and biopsy.

To further complicate matters JH sent a sample of my 3+4 for Decipher testing but it was insufficient for testing (too small). There was not enough tissue left for a second test. I requested that they do an Artera AI test instead, still awaiting results. In the meantime, JH sent a sample of my 3+3 for Decipher testing which I told them will provide no useful information for risk stratification since it is not reflective of the more aggressive pattern 4 cells.

JH got the insufficient sample info from Veracyte on 8/4 and unilaterally decided to send the 3+3 sample on 8/24. I inquired on 9/1 on the status of my testing and they actually told me that they didn't know if Veracyte received the original sample yet and made no mention of the substitution sample or that they sent an insufficient sample to start with! I didn't believe them and contacted Veracyte directly and they told me what was going on, including sending me copies of their communications with JH detailing JH's which verified the deception.

So, I am still waiting for the 3+3 Decipher score (on 9/10 Veracyte told me no sample received and no response to their info request on 9/8), and the Artera results from my 7/6 biopsy. Unacceptable conduct on the part of JH which can result in delay of care. Due for another PSA test in one month and follow up appointment at JH.

I went out of my way to choose JH since they are a COE but the way they have handled this situation makes me question this decision. As it stands now with their botched sample I will have to make treatment decisions without having adequate information and could result in under/over treatment. I am considering changing to Penn (about one hour from my northern home) or Mayo Jacksonville (about 3 hours from my southern home).

My husband had been very regularly checked before his diagnosis, because of his PC family history. His lesion in the MRI looked very small. The urologist and radiologist said "early caught, if any", but the biopsy found Gleason 5 cells already. The post-OP-pathology confirmed the small size. My husband has been 58. It seems, unfortunately, that PC can start very aggressive right away! It does not always need a lot of time for radicalizing.

The pathology checked for cribiform, IDC and all Variants of invasions, common friends of Gleason 5 cells. They were all negative. Maybe that would have been different a year later or so, but who knows.

@bjroc
I received excellent dx and tx from Surgeon and Radiation Oncologist at Johns Hopkins.
And traveled significantly to be treated there.
I highly recommend this COE.
Best to all.