Hemoglobin Drop and Prognosis in Patients with Advanced Prostate Cancer

Abstract & Commentary

By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.

Synopsis: Anemia prior to therapy has been established as a negative prognostic factor for patients with metastatic prostate cancer. In the current report, secondary analysis of data derived from a trial of hormonal ablation (orchiectomy +/- flutamide) reveals that a drop in hemoglobin in the first 3 months of treatment is associated with reduced overall and progression-free survival. Thus, treatment associated anemia may be considered with a number of other factors (performance status, Gleason score, extent of disease and pre-treatment hemoglobin level) as an independent prognostic factor for survival.

Source: Beer TM, et al. The prognostic value of hemoglobin change after initiating androgen-deprivation therapy for newly-diagnosed metastatic prostate cancer: A multivariate analysis of Southwest Oncology Group Study 8894. Cancer. 2006 Jun 27; [Epub ahead of print].

Anemia is common among patients with prostate cancer, occurring in approximately 25% of patients with metastatic disease at the time of presentation. Prior work from Beer and colleagues1 clearly showed that the presence of anemia in this setting was associated with a lower likelihood of PSA normalization, shorter survival, and shorter progression-free survival. The objective of the current study was to characterize changes in hemoglobin level after the initiation of androgen-deprivation therapy (ADT) in previously untreated metastatic prostate caner patients. For this, data from patients enrolled in the Southwest Oncology Group Study S8894 were examined. This study compared orchiectomy with or without antiandrogen (flutamide) in men with metastatic prostate carcinoma in a randomized, double blinded, Phase III trial conducted between 1989 and 1994, the results of which have been published.2 Of the 1286 patients enrolled, complete data necessary for the current analysis was available on 817 patients. There was no difference in survival (disease- free or overall) between the current study subset and the overall group.

The 817 subjects were analyzed in quartiles on the basis of their pretreatment hemoglobin level (< 12 g/dL, 12.1-13.7 g/dL, 13.8-14.7 g/dL and > 14.8 g/dL). Overall, 3 months after initiating ADT, the mean hemoglobin level declined 0.54 g/dL. However, the mean hemoglobin level increased by 0.99 g/dL in patients in the lowest quartile (baseline hemoglobin < 12 g/dL) whereas it decreased 1.04 g/dL for those with hemoglobin levels 12.1 g/dL or above. After adjusting for potential confounders, including baseline hemoglobin levels, a decline in hemoglobin level after 3 months of ADT was associated independently with shorter progression free survival (hazard ratio [HR], 1.10 per 1 g/dL decline, P = 0.0035) and shorter progression-free survival (HR, 1.08 per 1 g/dL decline (P = 0.013). At three months, those whose hemoglobin fell the most (quartile 1, in which the decline in hemoglobin was > 1.6 g/dL) had a 31% higher chance of dying when compared to those in quartile 4, (in which the hemoglobin rose > 0.3 g/dL).

Commentary

The current analysis showed that a 3-month change in hemoglobin is a new prognostic factor in a multivariate analysis that included baseline hemoglobin as well as other known factors such as performance status, Gleason score and disease extent. This information may be of value for clinicians as they assess treatment response and develop strategies to enhance survival for those with more aggressive disease.

From a physiological perspective, the findings are also of interest. Erythropoiesis is supported by gonadal hormones and anti-androgen therapy would be expected to drop hemoglobin levels accordingly. However, for those with cancer-associated anemia, either because of direct marrow involvement or by inflammatory mechanisms, the therapeutic effect of ADT might be expected to counter the lack of androgen erythropoietic support. Thus, a decline in hemoglobin in the first 3 months of ADT may well be a reflection of a more aggressive cancer that is not responsive to hormonal ablation.

References

1. Beer TM, et al. Prognostic value of anemia in newly diagnosed metastatic prostate cancer: a multivariate analysis of southwest oncology group study 8894. J Urol. 172(6 Pt 1):2213-2217. Erratum in: J Urol. 2005;174:1156.

2. Eisenberger MA, et al. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med. 1998;339:1036-1042.