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Toxicity and risk factors after combined high-dose-rate brachytherapy and external beam radiation therapy in men ≥75 years with localized prostate cancer

Toxizität und Risikofaktoren nach kombinierter Hochdosis-Brachytherapie und perkutaner Bestrahlung bei Männern ≥75 Jahren mit lokalisiertem Prostatakarzinom

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Abstract

Purpose

Combined high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) is a favorable treatment option in non-metastatic prostate cancer. However, reports on toxicity and outcome have mainly focused on younger patients. We aimed to determine toxicity and biochemical control rates after combined HDR-BT and EBRT in men ≥75 years.

Methods

From 1999 to 2015, 134 patients aged ≥75 years (median 76 years; 75–82 years) were identified. Patients received 18 Gy of HDR-BT (9 Gy/fraction on days 1 and 8) with an iridium-192 source. After 1 week, supplemental EBRT with a target dose of 50.4 Gy was started (delivered in 1.8 Gy fractions).

Results

Median follow-up time was 25 months (0–127 months). No severe (grade 4) gastrointestinal (GIT) or genitourinary (GUT) toxicities were observed. In 76 patients (56.7%), 3D conformal radiation therapy (CRT) and in 34.3% intensity-modulated radiotherapy (IMRT) was applied. CRT-treated patients were at a 2.17-times higher risk (hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.31–3.57, p = 0.002) of experiencing GUT. GIT risks could be reduced by 78% using IMRT (HR: 0.22, 95% CI: 0.07–0.75, p = 0.015). Patients with a higher T stage (T2c–3a/b) were less likely to experience GIT or GUT (HR: 0.49, 95% CI: 0.29–0.85, p = 0.011 and HR: 0.5, 95% CI: 0.3–0.81, p = 0.005, respectively).

Conclusion

HDR-BT/EBRT is a well-tolerated treatment option for elderly men ≥75 years with a limited number of comorbidities and localized intermediate- or high-risk prostate cancer. IMRT should be favored since side effects were significantly reduced in IMRT-treated patients.

Zusammenfassung

Hintergrund

Die Kombination aus HDR-(high-dose-rate)-Brachytherapie (BT) und externe Strahlentherapie (ERBT) ist eine vorteilhafte Behandlungsoption beim nichtmetastasierten Prostatakarzinom. Die Berichte über die Nebenwirkungen und den Therapieausgang beschäftigen sich zumeist mit jüngeren Patientenkollektiven. Ziel der Analyse war die Evaluation der Toxizität und der biochemischen Kontrollrate bei Patienten ≥75 Jahren, die sich einer kombinierten HDR-BT/EBRT unterzogen haben.

Methoden

Von 1999–2015 wurden 134 Patienten ≥75 Jahren (Median 76 Jahre; 75–82 Jahre) identifiziert. Die Patienten erhielten 18 Gy einer HDR-BT (9 Gy/Fraktion an Tag 1 und 8) einer Iridium-192-Quelle. Die EBRT mit einer Zieldosis von 50,4 Gy (Einzeldosis von 1,8 Gy) begann nach einer Woche.

Ergebnisse

Das mediane Follow-up betrug 25 Monate (Spanne 0–127 Monate). Es bestanden keine schwerwiegenden akuten (Grad 4) gastrointestinalen (GIT) oder urogenitalen (GUT) Nebenwirkungen. Bei 76 Patienten (56,7 %) kam die 3‑D-konformale Bestrahlung (CRT) und in 34,3 % die intensitätsmodulierte Radiatio (IMRT) zum Einsatz. Bei CRT-behandelten Patienten bestand ein 2,17-fach erhöhtes Risiko (Hazard-Ratio [HR]: 2,17; 95 %-Konfidenzintervall [KI]: 1,31–3,57; p = 0,002) für GUT. Das GIT-Risiko konnte um 78 % bei der IMRT reduziert werden (HR: 0,22; 95 %-KI: 0,07–0,75; p = 0,015). Bei Patienten mit einem höheren T‑Stadium (T2c–3a/b) bestand eine geringere Wahrscheinlichkeit GIT oder GUT zu erleben (HR: 0,49; 95 %-KI: 0,29–0,85; p = 0,011 bzw. HR: 0,5; 95 %-KI: 0,3–0,81; p = 0,005).

Schlussfolgerung

Die kombinierte HDR-BT/EBRT ist eine sichere und gut verträgliche Behandlungsoption für ältere Männer ≥75 Jahren, die wenige Komorbiditäten und ein lokal begrenztes, mittel- bis hochgradiges Prostatakarzinom aufweisen. IMRT-Techniken sollten bevorzugt werden, da sich hierdurch die Nebenwirkungen signifikant reduzierten lassen.

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Authors and Affiliations

  1. Department of Radiotherapy and Radiooncology, Outpatient Center, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Anastassia Löser, Cedric Oliver Carl, Thorsten Frenzel, Andreas Krüll & Rudolf Schwarz

  2. Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Burkhard Beyer, Yamini Nagaraj & Markus Graefen

  3. Department of Anaesthesiology, Center of Anaesthesiology and Intensive Care Medicine, University Medicine Rostock, Schillingallee 35, 18057, Rostock, Germany

    Benjamin Löser

  4. Department of Radiotherapy and Radiooncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Cordula Petersen

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  1. Anastassia Löser
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Correspondence to Anastassia Löser.

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A. Löser, B. Beyer, C.O. Carl, B. Löser, Y. Nagaraj, T. Frenzel, C. Petersen, A. Krüll, M. Graefen, and R. Schwarz declare that they have no competing interests.

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Löser, A., Beyer, B., Carl, C.O. et al. Toxicity and risk factors after combined high-dose-rate brachytherapy and external beam radiation therapy in men ≥75 years with localized prostate cancer. Strahlenther Onkol 195, 374–382 (2019). https://doi.org/10.1007/s00066-018-1380-5

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