Patterns of Cancer Progression of Metastatic Hormone-sensitive PCa in the ECOG3805 CHAARTED Trial

[pjoshea13]

New CHAARTED paper below [1].

"Reliance on prostate-specific antigen (PSA) alone is an inadequate strategy to monitor patients undergoing treatment for metastatic hormone-sensitive prostate cancer. Prostate cancer can get worse on scans even with low PSA and/or no or small changes in PSA. Imaging should be added to PSA testing to monitor patients with metastatic prostate cancer."

Would Medicare pay?

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/328...

Eur Urol Oncol

. 2020 Aug 14;S2588-9311(20)30092-4. doi: 10.1016/j.euo.2020.07.001. Online ahead of print.

Patterns of Cancer Progression of Metastatic Hormone-sensitive Prostate Cancer in the ECOG3805 CHAARTED Trial

Alan H Bryce 1 , Yu Hui Chen 2 , Glenn Liu 3 , Michael A Carducci 4 , David M Jarrard 5 , Jorge A Garcia 6 , Robert Dreicer 7 , Maha Hussain 8 , Mario Alfredo Eisenberger 9 , Elizabeth R Plimack 10 , Nicholas J Vogelzang 7 , Robert S DiPaola 11 , Lauren Harshman 12 , Christopher J Sweeney 13

Affiliations expand

PMID: 32807727 DOI: 10.1016/j.euo.2020.07.001

Abstract

Background: ECOG3805 is a randomized trial of testosterone suppression with or without docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC). Deeper prostate-specific antigen (PSA) suppression is prognostic for outcome. However, the concordance of PSA rise and radiographic progression has not been examined previously in mHSPC, whereas this has been reported in metastatic castration-resistant prostate cancer.

Objective: To determine the patterns of progression by PSA and radiographic parameters in patients in ECOG3805.

Design, setting, and participants: We conducted a retrospective analysis of all patients in ECOG3805. Patients were classified according to the PSA level at progression (whether PSA level was below 2.0 ng/mL or not) and the type of progression event in the study (either PSA progression as defined by the study with or without clinical progression, or clinical progression alone). Baseline demographics, clinical outcomes, and patterns of progression were compared between the groups.

Results and limitations: One in eight patients had clinical progression below a PSA level of 2 ng/mL, and approximately 25% developed clinical progression in the absence of confirmed PSA progression. Overall survival from randomization was shorter in patients with clinical progression without confirmed PSA progression than in patients with PSA progression alone as the first progression. Patient demographics at study entry were not predictive of the pattern of progression. Study limitations include its retrospective and post hoc nature.

Conclusions: Clinical progression prior to PSA rise or at low PSA levels is a relatively frequent phenomenon in mHSPC and is associated with poorer overall survival. Further biological and clinical studies of these patients are warranted.

Patient summary: Reliance on prostate-specific antigen (PSA) alone is an inadequate strategy to monitor patients undergoing treatment for metastatic hormone-sensitive prostate cancer. Prostate cancer can get worse on scans even with low PSA and/or no or small changes in PSA. Imaging should be added to PSA testing to monitor patients with metastatic prostate cancer.

Keywords: Chemotherapy; Clinical trial; Hormone therapy; Prostate cancer; Prostate-specific antigen.

Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

[LearnAll]

Agree. PSA alone..is not an accurate measure of progression....but a more accurate measure might be a combination of biomarkers and tracking them simultaneously...such as PSA, ALP, Albumin, Hb%, CRP, LDH, S Calcium T level...along with performance status and presence or absence of symptoms esp. pain level.

When we get a composite picture of all the above mentioned parameters, we might be almost as accurate as scans. Conventional scans themselves have their own problems with high sensitivity and low specificity as scarring, active inflammation and old injury marks etc can show and can get misinterpreted as active metastatic lesions.

IMHO, The ideal method will be the composite parameter tracking mentioned above ... along with scans.

[Hidden in reply to LearnAll]

I added LDH to my list. What do you think of HS-Crp, WBC components and ratios, liver enzymes (AST, ALP, ALT), ESR, TNFalpha?

[LearnAll in reply to Hidden]

LDH: This is an enzyme which tells if too much lactate is being produced by cancer cells ..indirectly giving clues about growth of cancer cells. It keeps going up each month..an upward trend for 6 months or more..its a red flag and possibility of Neuro endocrine differentiation should be entertained.

Hs-CRP: No need to check Hs type as it only is checked in case of heart problems. For PCa purpose, we only need to know extent of systemic inflammation in body..and for that C-Reactive protein (regular ) is sufficient. Should be kept below 1.0

To keep an eye how liver is handling the meds or getting adversely affected, we need to keep an eye on AST, ALT, Albumin. If they are all in normal range, liver seems to be doing fine.

ESR: another indicator of overall systemic inflammation. If you are already testing CRP

then there is no need to do ESR.

ALP: Alk Phosphatags is the best biomarker to know status of bone mets (osteoblastic activity a. k. a. bone repair activity. Generally, total ALP is sufficient as 50 to 60% of it comes from Liver and almost all of rest comes from bone repair activity. At times, we want to be more accurate in assesing state of our bone mets and that time we need Bone Specific Alkaline phosphatase (BALP) . Its more accurate , precise and more expensive.

Lastly, TNF alpha...this is a highly sophisticated test which tells a specifically about level of TNFalfa which is an inflammatory enzyme. I will leave this one to very wealthy people to do it since we average folks do not need this "luxury test." Its not necessary.

We also should track our NLRatio, PLRatio and LM ratio...these can be calculated very easily by our CBC test results. NLR should be below 3.0, LMR should be above 3.0 and PLR should be below 100. They are not only for purpose of monitoring cancer cell activity via inflammatory system at a given point of time but are also prognostic indicators.

Knowledge protects us from fear mongerers ...Best of luck.

[snoraste]

I’m hearing PSMA Scans will be FDA approved this fall. Hopefully.

[Hidden]

One of Dr Eugene Kwon's YouTube videos specifically mentions this. His patients had low PSAs yet after a choline scan, they were lit up with new sites. Here it is: youtube.com/watch?v=Nkqizmv...(Not working as expected?) start at 13:00 minute marker. Imaging is everything.

[LearnAll in reply to Hidden]

Ha Ha Ha ...We are all scared now to death by watching this fear mongering video. Show us some more scary videos so we can develop strong immunity against fear mongering.

This dude, Kwon.. is really good at what he does. He selected a few scans out of a million prostate cancer patients..the worst ones for the purpose to scare every patient . Fearful people become very vulnerable to exploitation. The real truth is that over 99% PCa sufferers Do Not have scans lighting anything if their PSA is below 0.2. So Say "F..u " to fear mongering and live life fearlessly. Identify fear mongerers and ignore them.

[Hidden in reply to LearnAll]

From the study: "Results and limitations: One in eight patients had clinical progression below a PSA level of 2 ng/mL, and approximately 25% developed clinical progression in the absence of confirmed PSA progression." Well, one in eight is 12.5% and 25% is double that so your "over 99%" are clear as a morning sky might be a wee bit on the high side. Regardless, I just added that as Kwon does show examples of that 12.5/25% who don't show excessive PSA levels or PSA progression yet have other tumours show in a follow-up scan. Imaging is indeed a valuable tool.

[j-o-h-n in reply to LearnAll]

Identify fear mongeres and ignore them..... easy as kwon, two, three....

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 08/19/2020 4:50 PM DST

[Wife32 in reply to LearnAll]

Unfortunately my young husband is one of these men, and we’ve met many others. His latest scans showed lesions with. a psa of 0.67. And it has been confirmed by 3 of the leading cancer centers to NOT be neuroendocrine. Previous lesions were found with psa as low as 0.12. FYI his prostate was removed so his psa should be non detectable.

The take away for me is that every cancer Is different. There are no absolutes in fighting this disease, so I try to keep an open mind and look into all options. Best of luck to all!

[Schwah]

Very interesting study. Thanks for posting. Question. I am hormone sensitive and I am having a second psma test at ucla to determine any progression. The first was negative. But if low psa in hormone sensitive men can still allow for clinical progression, perhaps that clinical progression wouldn’t show up on a psma scan since it’s looking for psa avid cancer. Do you think that means if my psma scan is negative, I should have a different second scan to look for non psma avid cancer? Dr. Czernin who runs the PSMA scabs at ucla indicated an FDG or other scan is not needed but now I wonder. Or does he say that because the psma scan is also a PET Scan?

Steve.

[LearnAll in reply to Schwah]

Steve, You are going to see respected Dr Sholtz. Please let me know what he says about this issue of progression with extremely low PSA and about FDG and PSMA scans .

[Schwah in reply to LearnAll]

Will do. I also intend to ask the ucla Radiolgist tomorrow at my scan.

Schwah

[Wife32 in reply to Schwah]

My husband’s progression showed on a psma and c-11 choline with a 0.48 Psa. He has had multiple, single lesion progressions with very low Psa. He is also hormone sensitive and not on any systemic treatments.

Very best of luck to you. Please keep us posted on your progress.

[5_plus_4]

Thank you for posting this. This describes my situation exactly. This leads me to believe that my MO is unaware of this research or just doesn't care about me because he has me on Lupron only with no scans scheduled.

[pjoshea13 in reply to 5_plus_4]

I suspect that many are too busy to read the journals, or perhaps he doesn't get the European Urology Oncology journal?

Even so, CHAARTED is one of the trials he should keep tabs on.

-Patrick

[TheTopBanana in reply to 5_plus_4]

Same here, no scans for my father Gleason 9. But the doctors argument was that the scan (PSMA) requires PSA to light up?

[treedown]

So when should this imaging start after the beginning of treament ? So PSMA scans are what is recommended as opposed to CT and Bone Scan? I am sure the insurance company won't pay for it before 2.0 or higher so is it worth paying OOP? If so at what point or PSA? Or are we talking random imaging?

[Doseydoe in reply to treedown]

I had a PSMA PET Scan when I was first diagnosed and another seven months later after being on ADT and having had Chemo. The first set a baseline of the extent of my APCa, and the second revealed the success of the treatments thus far. It made sense to me to identify the extent of the problem early so I knew what I was up against 😎 DD.

[treedown in reply to Doseydoe]

Not sure what country your in and it appears the extent of your disease at dx was more extensive than what imaging showed on me. Did you do this after bone scan and CT or in place? My main Drs wanted me to get Axumin PET due to PSA of 156 but insurance refused as it is not normally used here in first line treatment. They fought and did not win. My second opinion doc at SCCA mentioned going to LA for OOP but did not think it was worth it as it would not change my treatment. I have questions for next visit to MO and scans was #1 when this thread started. I will bring a copy of the abstract. I am undetectable so assume only a more advanced would show anything but may consider a OOP but the questions above remain. Thanks seems we started this about the same time, so and remembered your always cold post when I was checking you back around because I am as well.

[Doseydoe in reply to treedown]

G'day treedown, I'm located in Australia. The first scan I had was before DX which was a Renal Ultrasound. That showed a mass in my bladder and a non functioning left kidney, so my Dr. sent me to a Urologist who did a DRE. I then had a CT scan which confirmed an enlarged Prostate but was unable to show anything in the Bladder. That gave the green light for a Cystoscopy and Prostate biopsy, which revealed 22 cores of GS 9 in the left lobe of the Prostate. The Cystoscopy confirmed the presence of a mass in the Bladder which had closed off the left Ureter, hence no flow from the kidney. He couldn't put in a stent as he was unable to see the Ureter opening, so I had a separate procedure where they inserted a stent the other way (antegrade) from the kidney down to the Bladder. I had a PSMA PET Scan before I started chemo, which revealed three mets on my left Plevis, but again nothing in my Bladder. The reason given was that the marker/dye ends up in your urine in the Bladder and therefore masks any cancers, red on red in the imaging. So my take away from all this is that certain scans work best in different areas. The Ultrasound was good for showing the outline of the tumor in my Bladder. The CT scan was good for showing the size of my Prostate (able to be measured and detailed on the report). And the PSMA PET scan was good for checking all of my body to find where else the PCa had made its way to. For me that was my Pelvis. I am lucky it was not more extensive. So, that's my thoughts on scans, cheers 😎DD.