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Prognostic Factors for Survival in Noncastrate Metastatic Prostate Cancer: Validation of the Glass Model and Development of a Novel Simplified Prognostic Model

European Urology 2015 Aug;68(2):196-204

Abstract

Background

The Glass model developed in 2003 uses prognostic factors for noncastrate metastatic prostate cancer (NCMPC) to define subgroups with good, intermediate, and poor prognosis.

Objective

To validate NCMPC risk groups in a more recently diagnosed population and to develop a more sensitive prognostic model.

Design, setting, and participants

NCMPC patients were randomized to receive continuous androgen deprivation therapy (ADT) with or without docetaxel in the GETUG-15 phase 3 trial. Potential prognostic factors were recorded: age, performance status, Gleason score, hemoglobin (Hb), prostate-specific antigen, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), metastatic localization, body mass index, and pain.

Outcome measurements and statistical analysis

These factors were used to develop a new prognostic model using a recursive partitioning method. Before analysis, the data were split into learning and validation sets. The outcome was overall survival (OS).

Results and limitations

For the 385 patients included, those with good (49%), intermediate (29%), and poor (22%) prognosis had median OS of 69.0, 46.5 and 36.6 mo (p = 0.001), and 5-yr survival estimates of 60.7%, 39.4%, and 32.1%, respectively (p = 0.001). The most discriminatory variables in univariate analysis were ALP, pain intensity, Hb, LDH, and bone metastases. ALP was the strongest prognostic factor in discriminating patients with good or poor prognosis. In the learning set, median OS in patients with normal and abnormal ALP was 69.1 and 33.6 mo, and 5-yr survival estimates were 62.1% and 23.2%, respectively. The hazard ratio for ALP was 3.11 and 3.13 in the learning and validation sets, respectively. The discriminatory ability of ALP (concordance [C] index 0.64, 95% confidence interval [CI] 0.58–0.71) was superior to that of the Glass risk model (C-index 0.59, 95% CI 0.52–0.66). The study limitations include the limited number of patients and low values for the C-index.

Conclusion

A new and simple prognostic model was developed for patients with NCMPC, underlying the role of normal or abnormal ALP.

Patient summary

We analyzed clinical and biological factors that could affect overall survival in noncastrate metastatic prostate cancer. We showed that normal or abnormal alkaline phosphatase at baseline might be useful in predicting survival.

Take Home Message

The baseline characteristics of patients with noncastrate metastatic prostate cancer enrolled in a phase 3 study allowed validation of prognostic groups revealing phosphatase alkaline as a strong prognostic factor for overall survival.

Keywords: Prostate cancer, Noncastrate, Metastatic, Docetaxel, Alkaline phosphatase, Prognostic factors.

Footnotes

a Medical Oncology Department, Institut Paoli-Calmettes, Marseille, France

b Biostatistics Department, Institut Paoli-Calmettes, and Aix-Marseille Université, UMR_S 912 (SESSTIM), Marseille, France

c Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Sud, Villejuif, France

d Medical Oncology Department, Centre François Baclesse-CHU Côte de Nacre, Caen, France

e Medical Oncology Department, Centre Hospitalier Les Oudairies, La Roche-sur-Yon, France

f Institut Paoli-Calmettes, and Aix-Marseille Université, UMR_S912 (SESSTIM), Marseille, France

g Radiotherapy Department, Clinique Pasteur, Toulouse, France

h Department of Medical Oncology, Centre Paul Papin, Angers, France

i Medical Oncology Department, Centre Alexis Vautrin, Vandoeuvre-les-Nancy, France

j Medical Oncology Department, Centre Eugène Marquis, Rennes, France

k Surgical Urology Department, Institut Paoli-Calmettes, Marseille, France

l Medical Oncology Department, Centre René Gauducheau, Saint-Herblain, France

m Medical Oncology Department, Hôpital Foch, Suresnes, France

n Medical Oncology Department, Groupe Hospitalier Saint Joseph, Paris, France

o Medical Oncology Department, Centre Antoine Lacassagne, Nice, France

p Medical Oncology Department, Centre Val d’Aurelle-Paul Lamarque, Montpellier, France

q Medical Oncology Department, Institut Claudius Régaud, Toulouse, France

r Medical Oncology Department, Institut Curie, Paris, France

s Medical Oncology Department, Centre Georges François Leclerc, Dijon, France

t R&D UNICANCER, Paris cedex 13, France

u Medical Oncology Department, Clinique Sainte Marguerite, Hyeres, France

v Medical Oncology Department, Hôpital Layné, Mont de Marsan, France

w Medical Oncology Department, Centre Hospitalier La Timone, Marseille, France

x Medical Oncology Department, Centre Régional Hospitalier, Metz-Thionville, France

y Medical Oncology Department, Hôpital Bretonneau, Tours, France

z Medical Oncology Department, Centre Hospitalier Dupuytren, Limoges, France

aa Medical Oncology Department, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium

bb Medical Oncology Department, Centre Catherine de Sienne, Nantes, France

cc Medical Oncology Department, Hôpital Saint-André, Bordeaux, France

dd Medical Oncology Department, Clinique Saint-Jean Languedoc, Toulouse, France

ee Medical Oncology Department, Institut Jean Godinot, Reims, France

ff Medical Oncology Department, Clinique Armoricaine de Radiologie, Saint-Brieux, France

gg Medical Oncology Department, Hôpital Saint-Louis, Paris, France

hh Urology Department, Centre Hospitalier Universitaire Rangueil, Toulouse, France

ii Medical Oncology Department, Georges Pompidou Hospital and Rene Descartes University, Paris, France

lowast Corresponding author. Medical Oncology Department, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, UMR1068 Inserm, 232 Boulevard de Sainte Marguerite, 13009 Marseille, France. Tel. +33 4 91223740; Fax: +33 4 91223618.