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The Value of C-Reactive Protein Levels in the Prediction of a Bio-Chemical Prostate Cancer Recurrence

JoelT profile image
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C-Reactive Protein (CRP) serum levels are sometimes thought to be a bio-marker of a bio-chemical recurrence (BCR) of prostate cancer post surgery. However, after this concept was evaluated by researchers it was determined that the addition of preoperative CRP did not improve the accuracy of the standard pre and postoperative models for the prediction of having a BCR.

The researchers did determine that preoperative CRP elevation is common in men with pathological features of aggressive prostate cancer and also in men who had BCR after surgery. It is true that CRP is an independent prognostic value; but it does not serve to add either prognostic or clinically significant information to standard predictors of outcomes.

nature.com/pcan/journal/vao...

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JoelT
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Darryl profile image
DarrylPartner

How does a man get his Crp checked?

JoelT profile image
JoelT in reply to Darryl

Very simple blood test. One small vial of blood and off you go.

pjoshea13 profile image
pjoshea13

I wish that the study had included albumin. The Modified Glasgow Prognostic Score [MGPS] is a simple way of figuring out which hospital patients are at greatest risk, following an operation for almost any serious condition, but it seems to be equally useful for predicting the outcome of any chronic condition.

There are many blood tests that can be used as markers of inflammation. e.g. fibrinogen, which becomes fibrin when blood clots are formed, is elevated when there is inflammation. The folks in Glasgow, Scotland, reduced inflammation to a laughably simple formula involving only C-Reactive Protein [CRP] & Albumin:

MGPS =0 - except when

MGPS = 1 if CRP > 10 mg/L, but

MGPS = 2 if CRP > 10 mg/L and albumin < 3.5 g/dL

What is the case for adding albumin to a prognostic model in PCa? From 3 very recent papers:

[1] "A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel."

(2015):

"Six risk factors individually associated with poor prognosis were included in the final model: ... albumin ≤4 g/dl (HR = 1.54) ..."

[2] "Prognostic value of a computer-aided diagnosis system involving bone scans among men treated with docetaxel for metastatic castration-resistant prostate cancer." (2016):

"In multivariate analysis, three factors were identified as significant independent prognostic biomarkers for {overall survival} after docetaxel; ... {albumin} (<3.9 vs ≥3.9; HR, 3.776 ..."

[3] "Prognostic factors for clinical outcomes in patients with metastatic castration resistant prostate cancer treated with sequential novel androgen receptor-directed therapies." (2016):

"After adjusting for potential confounders ... and lower pre-treatment levels of albumin were associated with shorter {PSA-progression-free survival } (HR: 0.56 ...)"

More than 10 years ago, a man who was heading up a west coast PCa group, told me that men with PCa & albumin < 4.0 do not do well. My albumin at diagnosis was 3.9. It was 4.6 last year.

There is no point testing for something that merely tells one how grim things are. If albumin is low &/or CRP is high, what should one do? Inflammation is a modifiable risk factor. IMO

Inflammation is not just an artifact of serious PCa. The mechanism is well-understood. PCa chronically activates nuclear factor-kappaB [NFkB]. This causes the transcription of a great many cell survival proteins. Some of these are enzymes that act on cellular arachidonic acid to produce serious inflammatory metabolites that promote progression. The enzymes include the familiar COX-2 & 5-LOX proteins.

Most of the phytochemicals that have been studied as perhaps being useful in PCa, are polyphenols. & they all have the ability to inhibit activation of NFkB. I feel that this is important. Rather than taking a COX-2 specific inhibitor, we need to go upstream & target NFkB.

I'm probably able to name 20 polyphenols, given time, & there is probably particular synergy between some, but a handful of cheaper polyphenols might do the job - at the proper dose.

What would be the proper dose?

In my view, target albumin is 4.5, & that is the most important marker for survival.

(Interestingly, albumin has been found to be be a marker for 5 year survival in people who are not even ill.)

Target CRP is actually zero. There is nothing good about CRP, but I haven't acheived zero yet.

Phyto-polyphenols are usually well-tolerated & doses can be ramped up without digestive problems. The exception is EGCG from green tea. Green tea extracts are toxic to the liver if taken at high doses.

The basic blood test panel includes albumin. Many of us, perhaps, have access to our albumin history, so there might not be a need to get a baseline test. <4.0 is not a good place, whereas >=4.5 is, IMO. A simple experiment - take high-dose polyphenols with every meal. Test in one month. If inflammation is controlled, there might also be a marked increase in PSADT.

IMO.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/266...

[2] ncbi.nlm.nih.gov/pubmed/268...

[3] ncbi.nlm.nih.gov/pubmed/266...

pjoshea13 profile image
pjoshea13

C-Reactive Protein is a marker for inflammation. Albumin can also be used as a marker of inflammation (see my original reply). The neutrophil-to-lymphocyte ratio [NLR] is yet another.

New meta-analysis below. "14 publications (15 cohorts) with 16,266 patients"

"The combining data showed that increased NLR predict poor {overall survival - a 38% risk increase} in PCa."

-Patrick

ncbi.nlm.nih.gov/pubmed/269...

Sci Rep. 2016 Feb 25;6:22089. doi: 10.1038/srep22089.

Prognostic significance of neutrophil-to-lymphocyte ratio in prostate cancer: evidence from 16,266 patients.

Gu X1, Gao X1, Li X1, Qi X1, Ma M1, Qin S1, Yu H1, Sun S1, Zhou D1, Wang W1.

Author information

1Department of Radiation Oncology, Peking University First Hospital, Beijing 100034, China.

Abstract

This study was aimed to investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with prostate cancer (PCa). A meta-analysis including 14 publications (15 cohorts) with 16,266 patients was performed to evaluate the association between NLR and overall survival (OS), progression-free survival (PFS)/recurrence-free survival (RFS) in PCa using hazard ratio (HR) and 95% confidence intervals (95% CI). The combining data showed that increased NLR predict poor OS (HR = 1.38, 95%CI: 1.22-1.56) and PFS/RFS (HR = 1.24, 95%CI 1.05-1.46) in PCa. Stratified analysis by PCa type, sample size, ethnicity and NLR cut-off value revealed that NLR showed consistent prognostic value in metastatic castration-resistant prostate cancer (mCRPC) patients and predict poor PFS/RFS in Asians, but not in Caucasians. These statistical data suggested that increased NLR could predict poor prognosis in patients with PCa.

PMID: 26912340 [PubMed - in process]

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