Advanced Prostate Cancer

Inflammation. [1] Neutrophil-to-Lymphocyte Ratio [NLR]

I have written perhaps too many posts on inflammation & prognosis. Inflammation is a treatable condition, in my view, which means that the patient can improve on his prognosis.

There are a number of markers of subclinical inflammation & the NLR is just one of them. It is often included in a basic blood test panel used at an annual medical. If not, one can calculate it from the Neutrophil & Lymphocyte numbers, which are usually reported.

This post is prompted by a new Italian study [1], but is a review of the PCa-NLR literature.

As with other inflammation studies, the emphasis continues to be on the prognostic value of the test. With a low pretreatment NLR one might do well, have lesser disease, respond to treatment, live longer, etc. With a high NLR - doom & gloom.

Serious disease results in inflammation, but we know how to counter inflammation. There is a study of healthy people (no suspicion of disease) where 5-year survival was affected by low level inflammation markers. Inflammation is not just indicative of disease, it is a major player in the outcome. A pernicious influence. Something to be avoided.

[2] Wikipedia: "In medicine neutrophil to lymphocyte ratio (NLR) is used as a marker of subclinical inflammation. It is calculated by dividing the number of neutrophils by number of lymphocytes."

The studies began in 2012: (skip to "Conclusion" at any time)

[3] "patients treated with ketoconazole"

"Risk factors associated with the {progression-free survival} outcome were a pretreatment NLR >3 and PSA doubling time (PSADT) <3 months and a prior response to a gonadotropin-releasing hormone agonist of <24 months or to an antiandrogen of <6 months."

[4] NLR prior to Docetaxel treatment.

[4a] "patients with castration-resistant prostate cancer treated with docetaxel"

"NLR was found to be correlated with only posttreatment psa levels. In the NLR ≤3 group, the PSA levels were statistically significantly lower than the other group"

[4b] "patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line docetaxel"

"Men who were treated with first-line docetaxel for mCRPC who had a low pretreatment NLR (≤3.0) had significantly longer {overall survival}."

[4c] "High NLR may be associated with an independent poor prognostic impact in post-docetaxel patients with mCRPC."

[4d] "Liver metastases, hemoglobin <12 g/dL, alkaline phosphatase >2.0× upper limit of normal (ULN), lactate dehydrogenase >1.2× ULN, and NLR >3 were associated with significantly worse {overall survival} in multivariable analysis."

[4e] "In the training set, both {derived} NLR ≥median (2) and duration of initial ADT <median (15 months) were associated with increased risk of death [hazard ratio (HR) 1.29 ... and HR 1.41 .., respectively] after adjustment for age, alkaline phosphatase, hemoglobin, and pain at baseline."

[4f] "The cut-off level of the neutrophil-to-lymphocyte ratio was set as the median value of 3.5 among all patients in this study."

" ... the median overall survival and progression-free survival were shorter in patients with a high neutrophil-to-lymphocyte ratio compared with those with a low neutrophil-to-lymphocyte ratio (15 vs 20 months ... and 9.5 vs 15 months ... respectively)."

[4g] "In this retrospective series, metastatic CRPC patients who started first-line docetaxel with a low pretreatment NLR had a significantly better survival."

[5] Radiation.

[5a] "an NLR ≥ 5 was selected as cutoff value for external validation. Multivariate analysis identified an increased NLR as an independent prognostic factor for clinical {progression-free survival} [hazard ratio (HR) 3.09 ...], {distant metastases-free survival} (HR 3.51 ...), and {overall survival} (HR 2.16 ...)"

[6] Radical Prostatectomy

[6a] "The value of 2.494 for NLR was found to be a cut-off value which can be used in order to distinguish recurrence according to Youden index. According to this, patients with a higher NLR value than 2.494 had higher rates of PSA recurrence with 89.7% sensitivity and 92.6% specificity."

[6b] "patients with a NLR >3 have a higher incidence of recurrence. In multivariate analysis including age, total PSA and NLR, NLR is the most important factor able to predict recurrence."

[6c] "High NLR was significantly related to unfavorable clinicopathological outcomes and worse BCR-free survival."

[6d] "Our findings suggest that the pretreatment NLR may be associated with pathological stage and lymph node involvement in PCa patients receiving RP, and that PCa patients with a high NLR may have a higher rate of biochemical recurrence following RP than those with a low NLR."

[6e] "Our results demonstrate that postoperative neutrophil-to-lymphocyte ratio is an independent factor for biochemical recurrence and overall survival in patients who underwent radical prostatectomy for prostate cancer."

[7] NLR prior to Biopsy.

[7a] "NLR, with or without combination with F/T PSA ratio, may function as a new biomarker to predict prostate cancer in men undergoing prostate needle biopsy."

[7b] "In univariate analyses, NLR was a significant predictor of prostate cancer detection"

[7c] "The GS 8-10 group had a significantly higher mean NLR compared to GS 5-6 (3.64 vs. 2.54 ...) and GS 7 (3.64 vs. 2.58 ...) patients."

[8] Xtandi (Enzalutamide)

[8a] "The median {Progression-free survival} was 3.2 months ... in patients with baseline NLR >3 and 7.4 months ... in those with NLR ≤3 .... The median {overall survival} was 10.4 months ... in patients with baseline NLR >3 and 16.9 months ... in those with baseline NLR ≤3 ..."

[9] Zytiga (Abiraterone acetate)

[9a] "SII and NLR might represent an early and easy prognostic marker in mCRPC patients treated with abiraterone."

SII = A systemic immune-inflammation index based on neutrophil, lymphocyte, and platelet counts.

...

Conclusion.

Change the numbers!

To follow: "Inflammation. How to Change the Numbers"

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/280...

[2] en.wikipedia.org/wiki/Neutr...

[3] ncbi.nlm.nih.gov/pubmed/229...

[4a] ncbi.nlm.nih.gov/pubmed/245...

[4b] ncbi.nlm.nih.gov/pubmed/245...

[4c] ncbi.nlm.nih.gov/pubmed/248...

[4d] ncbi.nlm.nih.gov/pubmed/249...

[4e] ncbi.nlm.nih.gov/pubmed/255...

[4f] ncbi.nlm.nih.gov/pubmed/260...

[4g] ncbi.nlm.nih.gov/pubmed/280...

[5a] ncbi.nlm.nih.gov/pubmed/256...

[6a] ncbi.nlm.nih.gov/pubmed/257...

[6b] ncbi.nlm.nih.gov/pubmed/260...

[6c] ncbi.nlm.nih.gov/pubmed/264...

[6d] ncbi.nlm.nih.gov/pubmed/264...

[6e] ncbi.nlm.nih.gov/pubmed/280...

[7a] ncbi.nlm.nih.gov/pubmed/263...

[7b] ncbi.nlm.nih.gov/pubmed/264...

[7c] ncbi.nlm.nih.gov/pubmed/266...

[8a] ncbi.nlm.nih.gov/pubmed/274...

[9a] ncbi.nlm.nih.gov/pubmed/277...

4 Replies
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Ty Patrick I'm going to read up. I'm just confused because I myself have different inflammatory diseases,,all for which there is no cure and the treatment doesn't work so tumeric, certain diet, etc help but I have looked for a way for 20 years to reduce all inflammation. I'm also aware it's a matter in any disease and it's what worries me about my dad and his pain or possible future pain. If you have discovered there's a cure all for inflammation, wouldn't there be a cure for arthritis and associated diseases? No disrespect, I truly appreciate the research and will read all. Thank you so much.

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Ty I have read all and I'm thoroughly impressed and hopeful. I misread and thought that there was a basis of saying cure inflammation..cure cancer. I stand corrected, and interested in any research and so appreciative of your work.

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How does one compute the NLR if the blood test provides Neutrophils Absolute value and the Lymphocytes are provided as a % value under Differential Automated. Sorry, my background is electrical engineering, not biology. Thanks for any guidance.

Reply

That's odd.

My last Life Entension (LabCorp] report shows:

"Neutrophils" %

"Lymphs" %

"Neutrophils (Absolute)"

"Lymphs (Absolute)"

But anyway, the percentage relates to the total white blood cell count.

So, unless I have messed this up:

NLR = [100 * N(abs)] / [WBC * L(%)]

-Patrick

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