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Defining biochemical recurrence after radical prostatectomy and timing of early salvage radiotherapy

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Definition eines biochemischen Rezidiv nach radikaler Prostatektomie und Initiierung einer frühen Salvage-Strahlentherapie

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Abstract

Background

The optimal prostate-specific antigen (PSA) level after radical prostatectomy (RP) for defining biochemical recurrence and initiating salvage radiation therapy (SRT) is still debatable. Whereas adjuvant or extremely early SRT irrespective of PSA progression might be overtreatment for some patients, SRT at PSA >0.2 ng/ml might be undertreatment for others. The current study addresses the optimal timing of radiation therapy after RP.

Patients and methods

Cohort 1 comprised 293 men with PSA 0.1–0.19 ng/ml after RP. Cohort 2 comprised 198 men with SRT. PSA progression and metastases were assessed in cohort 1. In cohort 2, we compared freedom from progression according to pre-SRT PSA (0.03–0.19 vs. 0.2–0.499 ng/ml). Multivariable Cox regression analyses predicted progression after SRT.

Results

In cohort 1, 281 (95.9%) men had further PSA progression ≥0.2 ng/ml and 27 (9.2%) men developed metastases within a median follow-up of 74.3 months. In cohort 2, we recorded improved freedom from progression according to lower pre-SRT PSA (0.03–0.19 vs. 0.2–0.499 ng/ml: 69 vs. 53%; log-rank p = 0.051). Patients with higher pre-SRT PSA ≥0.2 ng/ml were at a higher risk of progression after SRT (hazard ratio: 1.8; p < 0.05).

Conclusion

The vast majority of patients with PSA ≥0.1 ng/ml after RP will progress to PSA ≥0.2 ng/ml. Additionally, early administration of SRT at post-RP PSA level <0.2 ng/ml might improve freedom from progression. Consequently, we suggest a PSA threshold of 0.1 ng/ml to define biochemical recurrence after RP.

Zusammenfassung

Hintergrund

Der optimale Wert des prostataspezifischen Antigens (PSA) nach radikaler Prostatektomie (RP) zur Definition eines biochemischen Rezidivs und zur Initiierung einer Salvage-Strahlentherapie (SRT) ist noch immer umstritten. Während eine adjuvante oder extrem frühe SRT unabhängig vom PSA-Verlauf für einige Patienten eine Übertherapie bedeuten würde, wäre eine SRT bei einem PSA >0,2 ng/ml für andere eine Untertherapie. In der vorliegenden Studie wird der optimale Zeitpunkt der SRT nach RP untersucht.

Patienten und Methodik

In der 1. Kohorte wurden 293 Männer mit einem PSA von 0,1–0,19 ng/ml nach RP auf die Endpunkte weiterer PSA-Progress sowie Metastasen untersucht. Die 2. Kohorte bildeten 198 Männer, welche mit einer SRT behandelt wurden und deren progressionsfreies Überleben in Abhängigkeit vom PSA vor SRT (0,03–0,19 vs. 0,2–0,499 ng/ml) untersucht wurde. Multivariable Cox-Regressionsanalysen wurden zur Vorhersage eines Progresses nach SRT durchgeführt.

Ergebnisse

In der 1. Kohorte hatten 281 Patienten (95,9 %) einen weiteren PSA-Progress ≥0,2 ng/ml und 27 Männer (9,2 %) entwickelten im medianen Follow-up von 74,3 Monaten Metastasen. In der 2. Kohorte zeigte sich eine bessere Progressionsfreiheit, wenn die SRT bereits bei niedrigerem PSA initiiert wurde (0,03–0,19 vs. 0,2–0,499 ng/ml: 69 vs. 53 %; log-rank p = 0,051). Zudem zeigte sich ein erhöhtes Progressionsrisiko, wenn der PSA vor SRT ≥0,2 ng/ml betrug (Hazard Ratio 1,8; p < 0,05).

Schlussfolgerung

Bei der überwiegenden Mehrheit der Patienten mit einem PSA ≥0,1 ng/ml nach RP wird dieser im weiteren Verlauf auf ≥0,2 ng/ml ansteigen. Zusätzlich könnte eine frühe SRT bei einem PSA <0,2 ng/ml nach RP das progressionsfreie Überleben verbessern. Als Konsequenz schlagen wir eine PSA-Grenze von 0,1 ng/ml für ein biochemische Rezidiv nach RP vor.

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Correspondence to Jonas Schiffmann MD.

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Conflict of interest

L. Budäus, J. Schiffmann, M. Graefen, H. Huland, P. Tennstedt, A. Siegmann, D. Böhmer, V. Budach, D. Bartkowiak, and T. Wiegel declare that they have no competing interests.

Ethical standards

This article does not contain any studies with human participants or animals performed by any of the authors. Consent was obtained from all patients identifiable from images or other information within the manuscript. In the case of underage patients, consent was obtained from a parent or legal guardian.

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L. Budäus and J. Schiffmann contributed equally to the manuscript.

Caption Electronic Supplementary Material

66_2017_1140_MOESM1_ESM.tif

Supplementary figure: Kaplan–Meier plot of freedom from progression, calculated from the time of prostatectomy to endpoint/censoring

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Budäus, L., Schiffmann, J., Graefen, M. et al. Defining biochemical recurrence after radical prostatectomy and timing of early salvage radiotherapy. Strahlenther Onkol 193, 692–699 (2017). https://doi.org/10.1007/s00066-017-1140-y

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  • DOI: https://doi.org/10.1007/s00066-017-1140-y

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