Is neutrophil count a marker for risk of prostate cancer mortality?

A recent article in the journal BMC Cancer has suggested a strong association between neutrophil count and risk for overall mortality among a cohort of Canadian men treated for prostate cancer with radiation therapy ± androgen deprivation therapy (ADT).

The new paper by Bahig et al. (which is available as a full text article) is based on a retrospective analysis of data from a cohort of > 1,700 patients with localized prostate cancer, all treated with definitive external beam radiotherapy or brachytherapy between September 2001 and June 2014 at a single Canadian institution. The authors were seeking to clarify the influence of markers of systemic inflammation such as leukocyte counts and metabolic co-morbidities on overall survival (OS) after radiotherapy for localized disease.   The so-called “absolute neutrophil count” or ANC is the real number of white blood cells (WBCs) that are neutrophils — the most abundant of the white blood cells, and an essential component of any person’s immune system.

Here is a summary of the findings reported by Bahig et al.:

  • The total patient cohort included 1,772 patients.
  • Blood count data was available for 950/1,772 patients (53.6 percent).
  • Average (median) follow-up  for all 1,772 patients was 44 months (range 1 to 156 months).
  • Average (median) age for all 1,772 patients was 68 years (range, 44 to 87 years).
  • Actuarial 5-year overall survival for all 1,772 patients was 93 percent.
  • Actuarial 5-year biochemical recurrence-free survival for all 1,772 patients was 95 percent.
  • On univariate analysis, neutrophil count (p = 0.04), cardiac history (p = 0.008), age (p = 0.001) and CAPRA score (p = 0.0002) were all associated with overall survival.
  • On multivariate analysis, neutrophil count (hazard ratio [HR] = 1.18, p = 0.028), age (HR = 1.06, p = 0.008), and CAPRA score (HR = 1.16, p = 0.015) were independent predictors of overall survival.
  • There was no association between neutrophil count and biochemnical recurrence-free survival on multivariate analysis.

Thus, first and foremost, before anyone starts to over-think this association, we are going to need to see it confirmed in at least one other, large cohort of patients. While there have certainly been other suggestions that there is a close relationship between systemic inflammation and the development and progression of a variety of cancers, we need to be very sure that this is the case for prostate cancer before we start to incorporate neutrophil levels into nomograms designed to project prostate cancer survival. Furthermore, one has to ask whether there is any possibility that this finding is in some way related to the fact that all these men were treated with radiation therapy.

The authors themselves note that this study comes with all sorts of inherent limitations. It was retrospective. Leukocyte data was not available for all patients. Data for other known inflammatory markers such as C-reactive protein and albumin level could not be included in the analysis. And only a very small proportion of the patients in the study had actually died during the follow-up period.

On the other hand, is it interesting that there is this apparently clear association between neutrophil count and risk for overall mortality? Yes, it certainly is. And we are going to need to see more data on this topic if we are to get to the bottom of this initial finding.

8 Responses

  1. Another study this year looked at the prognostic value of the neutrophil-to-lymphocyte ratio (NLR), and unlike Bahig et al., they did find an association between NLR and overall survival. They were both retrospective studies.

    Your conjecture that the results may be affected by radiation because of its pro-inflammatory effects makes a lot of sense to me.

  2. As a radiation/ADT patient with neutrophils tracked for years, I was interested in the details of this study. After looking at the complete paper, my impression is that this work is still quite preliminary and tentative. In fact, in the discussion, the authors considered the relationship of neutrophils to overall survival too weakly based to mention values of interest.

    That said, in a few years this work may bear fruit.

  3. From one of the authors: neutrophils were determined before any radiotherapy.

  4. Mea culpa. I should have made that perfectly clear in the original commentary above.

  5. Are they saying that higher number of neutrophils leads to better overall survival … or lower is better?

    I got a bit confused reading this.

  6. Jerry:

    They are saying that a higher than normal neutrophil count (which is indicative of inflammatory disease of some type) is associated with a lower overall survival. … But a lower than normal neutrophil count wouldn’t be good for other reasons.

  7. That just seems odd to me. According the definition … “…they are a type of immune cells that are one of the first cell types to travel to the site of an infection. Neutrophils help fight infection by ingesting microorganisms and releasing enzymes that kill the microorganisms. A neutrophil is a type of white blood cell, a type of granulocyte, and a type of phagocyte.”

    Seems to me you’d want more of these.

  8. Jerry:

    It’s not that simple. Neutrophil levels reflect the presence of infection and other immune system stimulation. They go up in number when there is an infection that needs to be “fought” by the immune system and they go down again to a “normal” level when there is no infection. However, if one’s neutrophil levels are high, then there are other consequences that can occur. Look at what happens to a child who gets a bad case of the ‘flu. She gets hot; she has fever; she gets tired/exhausted, and may be bedridden; and sometimes she dies. High levels of specific types of white cells are far from always being a good thing. Most of the time one needs to have a relatively normal “balanced” number of neutrophils in one’s system (not too few and not too many).

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