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The Gray Area of Favorable Intermediate Risk 3+4=7
There has been much discussion on this thread about how to approach favorable intermediate risk 3+4=7 PCa. Many on here have been adamant that active surveillance (AS) is the best or even the only acceptable approach. Evidence in support of active surveillance has included a video from esteemed pathologist Dr. Epstein and the popular YouTube videos by urology oncologist Dr. Mark Schulz from his Prostate Cancer Research Institute. I want to post a rebuttal of caution to the claims on this thread.
Even Drs. Epstein and Schulz offer a myriad of caveats to choosing active surveillance. These caveats include genetics, family history, size and location of lesions, volume of grade 4, number of positive cores, cribriform, intraductal, and perineural invasion. But even these popular doctors could not give a definitive answer for choosing active surveillance.
Dr. Walsh offers a summary of research and recommendations for favorable intermediate risk 3+4=7 PCa in his commonly accepted definitive book Guide to Surviving Prostate Cancer. He notes that the good news is that men with favorable intermediate risk 3+4=7 PCa have an excellent prognosis. Walsh writes that a cure is attainable with a single treatment - surgery or radiation. On page 134 Walsh states,
“Most men with intermediate-risk prostate cancer should consider curative treatment with either surgery or treatment. In some very selective cases, in men who have a low PSA and very little Gleason 3+4=7 cancer, active surveillance can be considered.”
Walsh goes on to state that men who have one core of 3+4 with limited amounts of cancer might be candidates for AS. But he strongly recommends genomic testing to identify more aggressive cancers.
On page 266, Walsh cites Dr. Ross from Northwestern University where she stated,
“I think for men with favorable intermediate-risk disease and high volume low-risk disease, active surveillance could be considered, but patients need to be aware of a few things.”
Walsh goes on to argue that the best studies on active surveillance from Johns Hopkins and Memorial Sloan Kettering contain selection biases - the researchers selected only the best candidates who are more likely to demonstrate success with AS. But it was noted that even with these biased samples, the average time on AS before needing treatment was 6.5 years. Ross is quoted as saying,
“The outcomes of active surveillance for men with higher volume, low risk disease and favorable intermediate-risk prostate cancer are, to a large extent, unknown.”
It is noted by Walsh that even Dr. Epstein agrees that biopsies can miss cancer cells under representing the grade or extent of cancer. We’ve read of many on this forum who upon radical prostatectomy, had their grading increased and that was born out in the Johns Hopkins and Sloan Kettering studies.
I bring this topic to the attention of this group for several reasons. I am a favorable intermediate risk 3+4=7 prostate cancer patient who chose treatment rather than active surveillance. I’m a patient at a university center of cancer excellence and have consulted with a broad team of medical professionals and discussed the options with my family. I’m having a radical prostatectomy next week. It is disheartening to read non medical professionals on this thread pushing active surveillance for all or most favorable intermediate risk 3+4=7 prostate cancer patients when the research is unclear. This makes one question their treatment decisions. Making definitive recommendations for this gray area lacking research is tantamount to a dereliction of responsibility to our fellow prostate cancer members. While perhaps some read a lot or watch lots of videos, we are not medical professionals. Men and their families are struggling with making treatment decisions and are reading social media threads or watching videos for advice. If men with favorable intermediate PCa make an active surveillance decision without the consultation of their own medical professionals, I’m afraid that several years down the road, there are going to be some very sorry patients because their cancer spread or got worse making treatment more difficult.
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Thanks for sharing this experience. I'm sorry for your post prostatectomy pathology report. But thank goodness you had the procedure and got the true picture of what was lurking. May you and your medical team agree on a viable treatment plan going forward so you can still enjoy those many years with your family.
Hi @rlpostrp I have a very similar story. 50 yo with PT3b with positive margins, I meet with MO/RO in a few weeks. Will probably be doing ADT and radiation.
I think even our stage is better than 5-10 years though. Hope everything works out for you!
In deciding the difficult decision AS, surgery, radiation, especially for intermediate favorable, there are other variable that need to be considered outside the obvious test results and MRI's. That is the human interpretation of results, and the variation present in test methods. To that point, I had two PI-RADS 4 tumors found in my MRI during my cancer experience, which indicate a high probability of prostate cancer. The MRI was initiated due to my rising PSA readings. After a guided biopsy from the MRI, the results showed no cancer present in the tumors. Was it because of a false negative or did they miss the target? Or am I just one of the lucky ones that don't have cancerous PI-RADS 4 tumors. It was a relief to find out there was no cancer, but the results would play in my decision later.
After 6 months, it was recommended that I have a second biopsy, and I was diagnosed with 4+3 on two samples, intermediate unfavorable. I decided to get a a second opinion by a pathologist at the university hospital know for there expertise. They reversed the diagnosis. The two 4+3 samples with more than 60% Gleason 4, were reversed to a 3+3 an 3+4 with less than 5% Gleason 4. The fact that two different pathologists could differ in their interpretation by that large of a margin was alarming to me. And so I thought back to the MRI results, the fact that two PI-RADS 4 tumors showed no cancer made me question the accuracy of those test results as well.
I had one other event that added to my anxiety, and this was regarding my PSA. My PCP at my physical reported that my PSA was 9.9. I had my PSA taken by my urologist a week earlier and it was 8.3. The two doctors work for different hospitals and use different diagnostic companies. When I went in for my second biopsy a few weeks later, I informed my urologist of the high reading from my PCP, so he took my PSA again. It was 8.4 very close to the last 8.3 PSA I had at their office. Now I understand that certain circumstances can effect the PSA, but I never considered a 1.5 difference in PSA readings over a few week period. And after experiencing some previous unusual results, I question the accuracy of the readings taken from two different diagnostic companies.
When I considered the variation from the interpretation of biopsy samples, the potential for missing the targets in a targeted biopsy, the variation in PSA analysis from different companies, I realized that you can't take all the results at face value. That's the point I am trying to make in this post. Either I am the most unlucky person or these things are happening more often than not. Add that to the fact the prostate cancer cases have increased at a 3% annual rate over the last 10 years, its not hard to be skeptical. Is it truly an epidemic of prostate cancer or is it a combination of over zealous physicians, aided by variations in test methods and the inexact science by pathologists interpreting the amount of cancer present. My urologist wanted to cut out the prostate when it was determined that I only had one sample with Gleason 4. My urologist wanted to radiate with the same information.
I'm just sharing some food for thought that everyone should take everything into consideration. I made my decision in spite of all the noise. Sharing information is healthy even if we're not doctors. Making a decision on what to do when you have a small amount of cancer is tough. My doctors didn't help. In the end, it was from reading personal experiences of others that helped me make my decision.
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5 ReactionsThx for the comments as I too am a Gleason 7 (3+4), 10%, 1 lesion in 12 per the biopsy; no crib, with PNI, PSA is 9.29. It's a challenge to make a decision. Some would say clearly do AS; some would say get rid of the cancer by surgery or radiation. However, I am inclined (as of today) to move towards focal treatment, a very hopeful middle option which unfortunately was not even mentioned in the string of comments. The FDA has approved several treatments and some are covered by Medicare/Insurance plans. I like this option for me because it addresses the cancer which as one comment pointed out can still continue to grow and make subsequent treatment more complicated. Plus the side effects are significantly less than surgery or radiation. I wish there was a decision tree for focal treatment selection, but I haven't been able to find one. Also, it is really unfortunate that the medical bureaucracy is so slow to realize and accept these newer treatments. Thx for the comments!
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2 ReactionsThat was an interesting first post-surgery discussion. Must’ve been a real shocker!
Leaving prostate tissue behind - healthy or cancerous - sometimes (unfortunately) happens. Dr. Kwon talks about this in one of his presentations about prostate recurrence: https://youtu.be/Q2joD360_pI
Genetic (germline) propensity of prostate cancer is said to occur in up to 15% of cases. However, there are also somatic propensities (e.g., mutated variants) caused by cell mutations or environmental factors. Other tests look at other genes, proteins, and tumor markers in prostate cancer. (This is not the same as genetic testing.). There may be some familial environmental similarities that are not known. Did your doctors investigate those?
Excellent point about focal therapies as 3+4=7 with certain types of lesions tend to make the best candidates. My surgeon does cryotherapy and we discussed it as an option. And it's covered by insurance. He told me that the effectiveness is less than surgery or radiation and it doesn't remove future potential lesions. But options for additional treatment remain.
Did you choose a focal therapy? Which?
Thanks for the comments. I was referred to Genetic Screening and Counseling (the later if necessary). A week or so after a buccal swab process, I was contacted and also sent an e-mail with a report that stated "Negative" for tumor genetic markers. I was a clinical lab director for most of my career. I was pleasantly and surprisingly shocked at how many genetic tumor markers are tested for. Without counting, it look to approach 100 or more. I will ask in my 3-month follow up at the end of July, if there is anything more specific that they can test for, and/or if any in-common environmental factors could be at play. Having been that clinical lab director, I had/have never heard of any environmental factors being contributory to prostate cancer. I have always known that there "can be" a familial genetic propensity for it )which I thought I had), but that most men - like me - fell into the classic "one in five men will get prostate cancer in their lifetime" category. Despite my father having prostate cancer, but living to age 99 years 10 months without treatment or prostatectomy; or my maternal grandfather having prostate cancer without prostatectomy for over 20 years and dying of Alzheimer's; and a maternal uncle having prostate cancer with prostatectomy, but dying of a massive stroke at age 86, there was no genetic link to my father's side of the family or my mother's side of the family. I just fell in that "one in five men will get prostate cancer" category.
Yes, genetic screening is typically known as “germline” screening - genetic testing that examines DNA in non-cancerous cells, like blood or saliva, to identify inherited gene mutations that might increase a person's risk of developing prostate cancers. It's distinct from somatic or tumor testing, which focuses on mutations within cancer cells - which are the other types of tests that I was referring to so that a more thorough view of the prostate cancer can be obtained (without cutting it out just to see).
Yes, there are a lot of gene mutations the genetic tests look at, but only a handful are currently known to be significantly related to prostate cancer. (See attached graphic.). Also note that the genetic predisposition can be passed down to men through the maternal line.
Many malignancies have been linked to specific environmental exposures. Some environmental and occupational factors have been linked to a risk of prostate cancer. These include Agent Orange exposure, pesticides, and industrial solvents like trichloroethylene.
Prostate cancer is highly survivable, especially when caught early. We’re talking 99% when caught in its earliest stages. The number often quoted for men diagnosed with prostate cancer is “1 in 8” (or “1 in 6,” if a minority), and a small subset of those actually die from prostate cancer. However, once it metastasizes, mortality increases significantly.
Genetics aside, just garden variety prostate cancer can be different for each generation. Your forbears lived in a different environment, and as you point out, we really don’t know specifically what different environmental, dietary or other factors contributed to YOUR cancer. Your father’s and grandfather’s cancers were probably not as aggressive (sorry to use that harsh of a word) - or as strong? - as yours. If they were, how could they live that long if statistics are to be believed?
FWIW - (and you didn’t ask me, I know) and please excuse my offering an opinion on this, but that’s all it is- an opinion; but in your shoes I would get on ADT now and have adjunctive RT as soon as you are cleared for it.
You know the cancer is still there and you know it is a more potent variety so why not get it as early as you can and kill it before it breaks loose? Best of luck with your treatment.
Phil
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2 ReactionsI’m still gathering info and opinions. As of today I’m thinking TULSA-PRO, although I like the precision of Focal Laser Therapy (FLA) but it hard to find info. FLA is approved and used in brain surgery so it’s not untested it seems. HIFU is available locally but I think the real-time MRI guidance of TULSA-PRO seems better to me. All the best.
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