Prostate cancer - repurposed drugs?

[Thunderball1]

I am 60 and have been diagnosed with localised, non-metastatic, low grade prostate cancer:

Grade 1/Gleason 6

cT2c

intermediate risk

65 cc size (moderate)

A detailed CT-PET scan (PSMA) (in addition to biopsy and MRI) lit up a fair bit and has shown moderate amount of bilateral disease but oddly in places not indicated on MRI or biopsy (anterior right), but various places. The urologist was concerned at the volume of disease (even if Grade 1) and suggests radical surgery and a referral to his mate who does the robocut. Seems overkill to me? I do not want to risk the side effects of ED (43-60% still have significant ED 2 years after surgery or radiation (e.g., UpToDate website peer-reviewed articles). I want AS if appropriate...with drugs to shrink the disease.

Biopsy: transperineal: "involving 15% of combined length of the tissue" in one "targeted" area on one side, no evidence in the templated area of that side...and only <5% of combined length on the other templated side. So that would be "less than half"?

Over on Advanced Prostate Cancer group TA said staging should only be by palpation and said my stage was wrong as imaging and biopsy should not be used. But biopsy is used for T1c?? I am following up with urologist to see what system if any he uses. Is it AJCC8 or grandpa's best guess? I do not know what the DRE result was. I am in New Zealand as they didn't bother to tell me (and I forgot to ask).

I have mild BPH.

I am keen to start the repurposed drugs/metabolic approach (e.g., COC protocol; Jane McLelland's book) and with any additional drugs recommended. I am very familiar with the approach as my wife survived rare sarcoma for 6 years and was on a modified COC protocol for that time. She passed away 2 years ago but her prognosis was only 20% chance of 5-year survival after she got mets so I believe the COC protocol was the key to 6-year survival.

My question is whether starting COC is a good idea for me now, even before prostate cancer has spread.

I am keen to hear the experiences and advice of others who may have taken this pre-emptive approach, which drugs in addition to the COC drugs did they use, and how they are progressing. A search on for "COC protocol" here brought up zero and "repurposed drugs" only two posts. Maybe folk are not familiar with the metabolic approach to starving cancer?

Here's a 2023 ref on repurposed drugs for cancer but there are hundreds on PubMed:

ncbi.nlm.nih.gov/pmc/articl...

Many thanks in advance.

[Justfor_]

The PSMA PET CT is the BEST tool in the toolbox. Don't measure it against anything else. cT staging was introduced when nothing else was available, so that docs had something (cryptic) to say that had the air of "scientific". Regardless of how it is derived it is nothing more than looking for black cats in dark dungeons. The only staging that has some (backwards) validity is the prostate pathology after prostatectomy. It is as "accurately" as one can be stratified in the PCa evolution scale at the time of slicing. Its prognostic value is a bit limited. You are in NZ. Your Aussie neighbors have long experience, second to the Germans, with PSMA PET CT. How about getting a tele-consult with one specialist from there. In particular, there is an ongoing (?) clinical trial studying the influence of a PSMA scan prior to prostatectomy. You may Google it and get the contact names of those behind it.

[Thunderball1 in reply to Justfor_]

Yes, my uro suggested it and basically assumed it supercedes/surpasses everything else like MRI and biopsy and he really trusts the PSMA. It seems following rather comments about staging on the other group ("staging is only to be based on DRE not imaging or biopsy!!!") I have asked him to re-check my staging. He gave me pT2c because MRI and biopsy had a small amount of bilateral Grade 1 and it was anterior (so hard to feel in principle he said, so I guess would be T1 if only using DRE. Why he wrote a "p" - pT2c - is a mystery to me. It should be cT2c, right? Anyway, on the basis of the scan he recommends robocut. I imagine he will be offended now for me not following "his" advice. They say "if it was me", but he is not me.

[Justfor_ in reply to Thunderball1]

Correct. "c" stands for clinical, while "p" for pathological. Your urologist is a "clinician", so not entitled to the preamble "p" however he came to devise the following letters. BUT, I will repeat it again here: Do not decide your future treatment on staging whatsoever!!! I for one was staged by my urologist as a T2b only to be upgraded by pathology to T3b.

Useful reading:

" ... A total of 431 patients with prostate cancer from 4 Australian centers had pre– and post–68Ga-PSMA management plans completed. Scans were obtained for primary staging of intermediate- and high-risk disease in 25% of patients and for restaging/biochemical recurrence in 75% of patients. Overall, 68Ga-PSMA PET/CT scanning led to a change in planned management in 51% of patients. The impact was greater in the group of patients with biochemical failure after definitive surgery or radiation treatment (62% change in management intent) than in patients undergoing primary staging (21% change). Imaging with 68Ga-PSMA PET/CT revealed unsuspected disease in the prostate bed in 27% of patients, locoregional lymph nodes in 39%, and distant metastatic disease in 16%."

jnm.snmjournals.org/content...

"... From March 22, 2017 to Nov 02, 2018, 339 men were assessed for eligibility and 302 men were randomly assigned. 152 (50%) men were randomly assigned to conventional imaging and 150 (50%) to PSMA PET-CT. Of 295 (98%) men with follow-up, 87 (30%) had pelvic nodal or distant metastatic disease. PSMA PET-CT had a 27% (95% CI 23–31) greater accuracy than that of conventional imaging (92% [88–95] vs 65% [60–69]; p<0·0001)....

canberraimaging.com.au/wp-c...

Finally, regarding the repurposed drugs that you seem to be your go to treatment they can only at best delay progression. I take statines for familial hypercholisterolemia since the mid 80s. They didn't protect me from getting PCa. Be advised that if you start Atorvastatine now, you will notice your PSA declining by 10-20%. I also take Berberine, like cujoe, which acts similar to Metformin.

[cujoe]

Thunderball - You just got a very good first response from a man with heroic Ελληνικά heritage. I would add re: repurposed drugs that there is much interest in both the medical world and patient community for their use in PCa and other cancers. The problem lies in the lack of the sort of trials that show efficacy and the unlikely chance for trials to be done for relatively cheap off-patent drugs. Without trials to protect them, not many MDs/MOs are going to be willing to write scripts for them.

The two most mentioned generic drugs among PCa patients seems to be metformin and one or more of the statin drugs. As PCa is most often a disease of older men, type 2 diabetes, overweight/obesity, lipid issues, and cardiac health also need to frequently be addressed. As a result, PCa patients here in the US often turn to their PCP (Primary Care Physician) for scripts for those conditions. For more exotic meds, people have been know to go to Canada for some and order via the wild-west of the internet for others. The inability to use repurposed drugs really is a lost source of potential game-changing treatment combos to augment SOC. As with most similar things, follow the money and there you will find your answers.

Best of Luck with the treat/no-treat treatment decision. Even with the additional scan info you have, it is a difficult "call". I was late to surgery, had non-confined disease, opted for early adjuvant RT, yet still had a BCR about 2 1/2 years later. I now have PSMA verified distant metastases, am Stage 4, and, with current treatment options, "incurable". That is not to scare you off from AS, just to serve as a warning to be extra vigilant with periodic labs and scans - so that you are not recounting a similar story to some 60-year old newly diagnosed man 10+ years down the road.

Most importantly, Stay positive, clean-up your diet and lifestyle, reduce/eliminate stress, get regular/restful sleep - and enjoy life while fully embracing the notion that none of us is getting out of here alive.

Best Regards,

Ciao - Kaptin K9

[Thunderball1 in reply to cujoe]

Thanks a lot K9. I appreciate all that advice. I am def going to take metformin and atorvastatin, possibly mebendazole and doxycycline which make up the big 4 of COC protocol. My GP won't prescribe unless he sees evidence so I need the COC letter of blessing from Harley Street. Unfortunately it's $1000 for the first consult. They doubled their price since my late wife used them 5 years ago for her sarcoma. That's cost of living crisis I guess...

Jane McLelland also emphasises quercetin. I'll post the supplements metro map for PCa...

[Thunderball1]

Supps metro map for PCa - COC protocol plus other repurposed drugs...it's a pdf so can't link. Here's the first page...

metro map

[cujoe in reply to Thunderball1]

TB1 - Good to have a plan for any treatment program. If possible, it should be monitored regularly to determine efficacy and possible component resistance or agonistic behavior.

No idea what sort of "walk-in" lab services exist in NZ, but I have been doing regular metabolic panels to monitor my own non-SOC program here in the US. Outside of clinical trials, it is difficult to get most cancer centers or urological practices here to do much more than PSA and T. (In fact my first T lab was at my RALP pre-op. At that time it was all of 127!!!! 10 years later, it is now bicalutamide-boosted to +800)

As for other supplements/nutraceuticals on the map, trans-resveratrol and quercetin are widely used. I've been using both (along with curcumin) for many, many years now. Concurrent use of berberine and metformin might be pushing things quite a bit. I have opted for the supplement, even though a generic of the pharma product would be much less expensive. I am planning to at least get a finger-prick glucose monitor soon. A continuous monitor would be a better tool, so I may try one after I see how the single sample monitoring works out.

As noted on the map, the use of DHEA continues to be controversial for PCa patients. Chromium picolate's split personality would seem to also suggest careful consideration for any PCa patient before using. Finally, since Doxycycline is an antibiotic, one needs to consider the disruptive risk to the ever important microbiome before using it or any other antibiotic. (IMO)

With supplementation as with all treatment decisions, it is best to look very carefully before you leap into any specific protocol. Our cancers are individually differentiated - and what works well for one person, might have zero benefit to another one.

Ease into any regime so that you can monitor the results. Good Luck and Better Health to you and yours. Ciao - Kaptin cujoe

[Teufelshunde]

I wonder how the supplements I use after a BCR would work in an AS world. Basically we have the same goal so may be worth a try. The one study shows it basically stops PSA increase, meaning it basically stops the disease progression. It is one of those "gold standard" studies. It is for sulforaphane. In US, the product used in the study is BROQ (broq.life or Amazon). I would only take it at the study dose (60mg/day) since it is shown that works. There is also a study that shows pomegranate juice 1c daily, also acts to slow PC growth. Not as good as sulforaphane but I take that as well. Last, modified citrus pectin also has some studies showing slowing pc growth. Add these to low dairy/meat diet and may help. There is certainly no downside to any of the above, other than some cost. Here are the studies.

aacrjournals.org/cancerprev...

pubmed.ncbi.nlm.nih.gov/168...

mdpi.com/2072-6643/13/12/42...

[cujoe in reply to Teufelshunde]

Teufelshunde - This video from NutritionFacts would suggest that you should view it not as an either/or when it comes to plant-sourced supplements, powders, and actual foods, but rather on ingesting rich combinations. (Microbiome guru, Dr. B, recommends eating at least 30 different food weekly - for a healthy gut flora that is home to +/-70% of our immune function!)

Broccoli sprouts are a much better and cheaper source of sulforaphane than you will ever find in a capsule and whole fruit pomegranate powder (vs juice powder) is a great addition to smoothies. In fact, as the video suggests, it is easy to more than match the ingredient composition of the supplement (that resulted from the trial profiled in the video) by simply eating a combo of the foods from which the ingredients are derived.

Flashback Friday: Best Supplements for Prostate Cancer, Michael Greger M.D. FACLM, NutritionFacts.com, November 12, 2021

nutritionfacts.org/video/fl...

Eat Well to Be/Stay Well,

Ciao - K9

PS: here is the supplement that was created from the trial:

lifeextension.com/vitamins-...

[Teufelshunde in reply to cujoe]

I understand Greger's view and not arguing, I think, however, that most of his cites are in lab dishes. Here is the way I look at this world of PC. If there is a placebo-controlled study testing a product, and it is done on men with PC, and especially with BCR, so it is basically ME (and I wonder if people on AS fall into this caatagory since I am basically on AS now after RP and STR), and that study shows the product and the dose of that produced that positive result, I am taking that product at the study dose. Period.

I understand sprouts may have other factors that are favorable, and do contain sulforaphane (or is the precursor what is eaten?-again way too many unknowns for me), but until I see a study on PC with men, sticking with the study.

So I have seen 3 studies I feel good about the results on BCR so I take that product.

Also, Pom-T was not the product used in the study you cite above for pomegranate juice. It was organic pomegranite juice. PomT has its own study and I tried to compare the two products studies based on the two different products and I was not scientific enough to compare. I only made it through environmental chemistry is college. Was a fun class with a little science.

My main point was that I think a person on AS can benefit from using things shown through clinical studies on men with BCR to work.

[cujoe in reply to Teufelshunde]

In all due respects, Pomi-T was the commercial product that resulted from the double-blind, placebo-controlled CT using the four plant ingredients.

pubmed.ncbi.nlm.nih.gov/246...

Ciao - K9

PS No funding conflict of interest in this study.

[Teufelshunde in reply to cujoe]

No issues my brother. Maybe I misstated what I was trying to say. The study that I cited in my post above re pomegranate was done with pomegranate juice of 1 cup per day. Here it is again. pubmed.ncbi.nlm.nih.gov/168...

I know there was a different study using Pomi-T that showed positive results also. That product is a mixture of items like you say.

Not sure which of the two, Pomi-T or straight 1 cup of organic pomegranate juice, produces a better result, since they use different measures in their results. I was hoping there was some science guru out there that could look at the two and tell which is better at slowing progression.

[cujoe]

TB1 - You might also want to watch this video interview from earlier this year with well-regarded PCa MO, Dr. Oliver Sartor (recently relocated to Mayo in MN). The NEJM Editorial mentioned in the interview, Localized Prostate Cancer - Then and Now, is also linked below. (Access to the full paper requires registration.)

Video is here:

15-Year Follow-Up of the ProtecT Trial: Discussing Results and Changes in Prostate Cancer Management, The ProtecT Trial - Oliver Sartor, UroToday Home, Video Lectures, Localized Prostate Cancer, Video, May 9, 2023

urotoday.com/video-lectures...

And NEJM Editorial is here:

Localized Prostate Cancer - Then and Now, Oliver Sartor, M.D., The New England Journal of Medicine, Editorial, April 27, 2023, N Engl J Med 2023; 388:1617-1618

nejm.org/doi/10.1056/NEJMe2...

Stay S&W,

Ciao - K9

[Thunderball1 in reply to cujoe]

See my comment on ProtecT below....

[Thunderball1]

Here is a summary from UpToDate on ProtecT trial. Screenshot captures the complete summary.

Do folks know about UpToDate? It's an amazing set of actually updated peer-reviewed summary articles - a go-to resource - but costs $50 a month but a week is less money. Log on for a short term and download all your chapters.

ProtecT trial

[cujoe in reply to Thunderball1]

Thanks for the sample screen shot from what is a new resource for me. Looks to be a good one. Not sure if there is any discrepancy between Sartor's update review and the one from Up To Date, but either way, it would seem to be a good way to stay up with long-term studies. It looks to be a very concise summary.

Ciao - Kaptin K9