Abstract
Purpose
The aim of the present retrospective study is to evaluate toxicity and early clinical outcomes of interstitial hyperthermia (IHT) combined with high-dose rate (HDR) brachytherapy as a salvage treatment in patients with biopsy-confirmed local recurrence of prostate cancer after previous external beam radiotherapy.
Patients and methods
Between September 2008 and March 2013, 25 patients with local recurrence of previously irradiated prostate cancer were treated. The main eligibility criteria for salvage prostate HDR brachytherapy combined with interstitial hyperthermia were biopsy confirmed local recurrence and absence of nodal and distant metastases. All patients were treated with a dose of 30 Gy in 3 fractions at 21-day intervals. We performed 62 hyperthermia procedures out of 75 planned (83 %). The aim of the hyperthermia treatment was to heat the prostate to 41–43 °C for 60 min. Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, v. 4.03). Determination of subsequent biochemical failure was based on the Phoenix definition (nadir + 2 ng/ml).
Results
The median age was 71 years (range 62–83 years), the median initial PSA level was 16.3 ng/ml (range 6.37–64 ng/ml), and the median salvage PSA level was 2.8 ng/ml (1.044–25.346 ng/ml). The median follow-up was 13 months (range 4–48 months). The combination of HDR brachytherapy and IHT was well tolerated. The most frequent complications were nocturia, weak urine stream, urinary frequency, hematuria, and urgency. Grade 2 rectal hemorrhage was observed in 1 patient. No grade 3 or higher complications were observed. The 2-year Kaplan–Meier estimate of biochemical control after salvage treatment was 74 %. The PSA in 20 patients decreased below the presalvage level, while 11 patients achieved a PSA nadir < 0.5 ng/ml. All patients are still alive. Of the 7 patients who experienced biochemical failure, bone metastases were found in 2 patients.
Conclusion
IHT in combination with salvage HDR brachytherapy is a well tolerated and effective treatment.
Zusammenfassung
Ziel
Die vorliegende retrospektive Studie bewertet die Toxizität und die frühen klinischen Ergebnisse der interstitiellen Hyperthermie (IHT) in Kombination mit HDR-Brachytherapie (Brachytherapie mit hoher Dosisrate, „high-dose rate“) als Salvage-Verfahren bei Patienten mit histologisch gesichertem Lokalrezidiv eines Prostatakarzinoms nach früherer externer Strahlentherapie.
Patienten und Methoden
Zwischen September 2008 und März 2013 wurden 25 Patienten mit Lokalrezidiv eines zuvor perkutan bestrahlten Prostatakarzinoms behandelt. Die Hauptselektionskriterien für das kombinierte Salvage-Verfahren einer HDR-Brachytherapie in Verbindung mit interstitieller Hyperthermie waren: histologische Sicherung eines Lokalrezidivs durch Biopsie und Abwesenheit von Lymphknoten- bzw. Fernmetastasen. Alle Patienten wurden mit der Dosis von 30 Gy in 3 Fraktionen in Abständen von 21 Tagen behandelt. Von den geplanten 75 wurden 62 Hyperthermieverfahren (83 %) durchgeführt. Das Ziel der Hyperthermiebehandlung war die Erwärmung der Prostata auf 41–43 °C für die Dauer von 60 min. Die Toxizität für die Organe des Harn- und Geschlechtssystems sowie des Mastdarms wurde anhand der Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03 bewertet. Die Bestimmung der nachfolgenden biochemischen Tumorkontrolle basierte auf der Phoenix-Definition (Nadir + 2 ng/ml).
Ergebnisse
Das Alter betrug im Median 71 Jahre (62–83 Jahre), der mediane prätherapeutische PSA-Wert 16,3 ng/ml (6,37–64 ng/ml) und der mediane PSA- Wert zum Zeitpunkt der Salvage-Behandlung 2,8 ng/ml (1,044–25,346 ng/ml). Die mediane Nachbeobachtungszeit lag bei 11 Monaten (4–48 Monate). Die Kombination der HDR-Brachytherapie mit IHT wurde gut vertragen. Die häufigsten Komplikationen waren: Nykturie, schwacher Harnstrahl, häufiges Wasserlassen, Hämaturie und Harndrang. Bei einem Patienten wurde eine rektale Grad-2-Blutung beobachtet. Es traten keine Komplikationen 3. Grades oder höher auf. Die Kaplan-Meier-2-Jahres-Schätzung der biochemischen Kontrolle nach der Salvage-Therapie betrug 74 %. Bei 20 Patienten fiel der PSA unter die Werte vor Salvage-Behandlung, 11 Patienten erreichten einen PSA-Nadir von 0,5 ng/ml. Alle Patienten überlebten. Einen biochemischen Rückfall erlitten 7 Patienten – bei 2 von ihnen wurden Knochenmetastasen gefunden.
Schlussfolgerung
Die Kombination aus IHT und Salvage-HDR-Brachytherapie ist eine gut verträgliche und effektive Therapieform.
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Compliance with ethical guidelines
Conflict of interest. A.M. Kukiełka, M. Hetnał, T. Dąbrowski, T. Walasek, P. Brandys, D. Nahajowski, R. Kudzia, D. Dybek, and M. Reinfuss state that there are no conflicts of interest.
All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance 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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Kukiełka, A., Hetnał, M., Dąbrowski, T. et al. Salvage prostate HDR brachytherapy combined with interstitial hyperthermia for local recurrence after radiation therapy failure. Strahlenther Onkol 190, 165–170 (2014). https://doi.org/10.1007/s00066-013-0486-z
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DOI: https://doi.org/10.1007/s00066-013-0486-z