Abstract
Background
The neutrophil to lymphocyte ratio (NLR) has been shown to be highly prognostic across
many tumor types, and predictive of treatment outcome in advanced prostate cancer,
and has been postulated to be an indirect measure of tumor inflammation. We evaluated
the effect of low-dose steroids on NLR in men suffering from castration-resistant
prostate cancer (CRPC).
Patients and Methods
The NLR was evaluated in a prospective randomized phase II trial that compared prednisolone
5 mg twice daily and dexamethasone 0.5 mg daily administered to 75 chemotherapy and
abiraterone/enzalutamide-naive CRPC patients. NLR was examined at baseline (BL), after
6 and 12 weeks of corticosteroid treatment; associations with >50% prostate-specific
antigen (PSA) response, duration of response (PSA progression-free interval), and
overall survival (OS) were tested using logistic regression and Cox regression analysis.
Results
The median NLR for all evaluable patients was 2.6 at BL; 2.9 at 6 weeks; and 4.0 at
12 weeks. After low-dose corticosteroid initiation, 46 patients had a decline in PSA
with 24 confirmed responders. BL NLR (log10) associated with a PSA response (odds
ratio, .029, 95% confidence interval [CI], .002-.493; P = .014), and with the extent of the PSA decline (P = .009). A favorable BL NLR (less than median) associated with a 5.5-fold higher
odds of a PSA >50% response (95% CI, 1.3-23.9; P = .02). Higher BL NLR (log10) associated with a shorter time to PSA progression (hazard
ratio [HR], 9.5; 95% CI, 2.3-39.9; P = .002). In multivariate analysis BL NLR as a discrete variable was independently
associated with PSA progression (HR, 3.5; 95% CI, 1.5-8.1; P = .003). NLR at 6 weeks was also associated with duration of benefit; in the favorable
NLR category time to PSA progression was 10.8 months, for those who converted to an
unfavorable (greater than median) category 4.5 months, and for those remaining in
a unfavorable category only 1.5 months (95% CI, 0.5-2.5; P = .003). OS was 33.1 months (95% CI, 24.2-42.0) and 21.9 months (95% CI, 19.3-24.4)
for those with an favorable and unfavorable BL NLR, respectively.
Conclusion
Treatment-naive CRPC patients with a high BL or during-treatment NLR appear not to
benefit from low-dose corticosteroids. The immunological implications of an unfavorable
NLR, and whether corticosteroids might drive prostate cancer progression in patients
harboring a high NLR, warrant further study.
Keywords
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Article info
Publication history
Published online: May 10, 2017
Accepted:
May 3,
2017
Received in revised form:
April 28,
2017
Received:
March 17,
2017
Identification
Copyright
© 2017 Elsevier Inc. All rights reserved.
