Abstract
Background
Nomograms were established to predict biochemical recurrence (BCR) after radiotherapy (RT) with a low weight of the characteristic variables of RT and androgen deprivation therapy (ADT). Our aim is to provide a new stratified tool for predicting BCR at 4 and 7 years in patients treated using RT with radical intent.
Materials and methods
A retrospective, nonrandomized analysis was performed on 5044 prostate cancer (PCa) patients with median age 70 years, who received RT—with or without ADT—between November 1992 and May 2007. Median follow-up was 5.5 years. BCR was defined as a rise in serum prostate-specific antigen (PSA) of 2 ng/ml over the post-treatment PSA nadir. Univariate association between predictor variables and BCR was assessed by the log-rank test, and three linked nomograms were created for multivariate prognosis of BCR-free survival. Each nomogram corresponds to a category of the Gleason score—either 6,7, or 8–10—and all of them were created from a single proportional hazards regression model stratified also by months of ADT (0, 1–6, 7–12, 13–24, 25–36, 36–60). The performance of this model was analyzed by calibration, discrimination, and clinical utility.
Results
Initial PSA, clinical stage, and RT dose were significant variables (p < 0.01). The model showed a good calibration. The concordance probability was 0.779, improving those obtained with other nomograms (0.587, 0.571, 0.554) in the database. Survival curves showed best clinical utility in a comparison with National Comprehensive Cancer Network (NCCN) risk groups.
Conclusion
For each Gleason score category, the nomogram provides information on the benefit of adding ADT to a specific RT dose.
Zusammenfassung
Hintergrund
Es wurden Nomogramme etabliert, um ein biochemisches Rezidiv (BCR) nach einer Strahlentherapie (RT) vorhersagen zu können und den Einfluss der charakteristischen Variablen der RT und der Androgendeprivationstherapie (ADT) dabei möglichst gering zu halten. Unser Ziel ist es, ein neues stratifiziertes Instrument bereitzustellen, mit dem sich ein BCR nach 4 und 7 Jahren für Patienten vorhersagen lässt, die mit radikaler Absicht strahlentherapeutisch behandelt wurden.
Material und Methoden
Zwischen November 1992 und Mai 2007 wurde eine retrospektive, nichtrandomisierte Analyse von 5044 Prostatakarzinompatienten mit einem medianen Alter von 70 Jahren durchgeführt, die eine RT mit oder ohne ADT erhalten haben. Die mediane Nachbeobachtungszeit betrug 5,5 Jahre. Ein BCR wurde definiert als ein Anstieg des PSA-Werts im Serum von 2 ng/ml im Vergleich zum PSA-Nadir nach der Behandlung. Die univariate Beziehung zwischen den Prädiktorvariablen und dem BCR wurde mithilfe des Log-Rank-Tests untersucht. Es wurden drei miteinander zusammenhängende Nomogramme für die multivariate Prognose des BCR-freien Überlebens etabliert. Jedes Nomogramm entspricht einer Kategorie des Gleason-Score, entweder 6, 7, oder 8–10. Alle Nomogramme wurden mittels eines einzigen proportionalen Hazard-Regressionsmodells etabliert, das auch nach Monaten der ADT (0, 1–6, 7–12, 13–24, 25–36, 36–60) stratifiziert wurde. Die Aussagekraft dieses Modells wurde anhand von Kalibrierung, unterschiedlicher Behandlung und klinischem Nutzen analysiert.
Ergebnisse
Anfänglicher PSA-Wert, klinisches Stadium und die Dosis der RT waren signifikante Variablen (p < 0,01). Das Modell wies eine gute Kalibrierung auf. Die Konkordanzwahrscheinlichkeit lag bei 0,779, was eine Verbesserung gegenüber anderen Nomogrammen (0,587, 0,571 und 0,554) in der Datenbank bedeutet. Die Überlebenskurven zeigten den besten klinischen Nutzen im Vergleich zu Risikogruppen der National Comprehensive Cancer Network (NCCN).
Schlussfolgerung
Für jede Kategorie des Gleason-Score liefert das Nomogramm Informationen über den Nutzen der ADT zusätzlich zu einer spezifischen RT-Dosis.
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Acknowledgements
We gratefully acknowledge the support provided by Ipsen (Boulogne-Billancourt, France) in the development and maintenance of the RECAP database.
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J. López-Torrecilla, A. Boladeras, M.A. Cabeza, A. Zapatero, J. Jove, L.M. Esteban, I. Henriquez, M. Casaña, C. González-San Segundo, A. Gómez-Caamaño, J.L. Mengual, A. Hervás, J.L. Muñoz, and G. Sanz state that there are no conflicts of interest.
All studies on humans in the present manuscript were carried out with the approval of the responsible ethics committee with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.
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López-Torrecilla, J., Boladeras, A., Cabeza, M. et al. Three linked nomograms for predicting biochemical failure in prostate cancer treated with radiotherapy plus androgen deprivation therapy. Strahlenther Onkol 191, 792–800 (2015). https://doi.org/10.1007/s00066-015-0866-7
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DOI: https://doi.org/10.1007/s00066-015-0866-7