Prospective Phase 2 Trial: Long-term results of a salvage brachytherapy combined with interstitial hyperthermia as Re-Irradiation for locally recurrent prostate Carcinoma.

[PURPOSE] This prospective Phase 2 trial investigates efficacy and side effects of ultrasound-guided salvage brachytherapy with interstitial hyperthermia in locally recurrent prostate cancer following previous radiation therapy.

[MATERIALS AND METHODS] Altogether 109 patients with locally recurrent prostate cancer after previous external beam radiation therapy were enrolled in this Phase 2, multicentric prospective trial between 2015 and 2020. Patients received either 30 Gy in three fractions 21 days apart (78.0 Gy, EQD2, α/ β = 3 Gy) using interstitial HDR-brachytherapy alone or 60 Gy in 2 sessions 28 days apart (71.5 Gy (EQD2, α/β = 3 Gy) using interstitial PDR-brachytherapy alone. We performed the interstitial brachytherapy in all patients with plastic needles. Additionally, interstitial hyperthermia treatment was executed within one hour before or during every brachytherapy fraction/series for a therapeutic time of 60 min and a target temperature of 40-41 °C, at least. The primary endpoint of this prospective phase 2 trial was rate of late Grade ≥ 3 gastrointestinal (GI) and genitourinary (GU) side effects. Treatment-related toxicity was evaluated according to the Common Toxicity Criteria for Adverse Events version 4.03 (CTCAE). Secondary endpoints were cumulative local recurrence rate, biochemical disease-free survival (bDFS), overall survival (OS), disease-free survival (DFS) and cancer-specific survival. This trial is registered with ClinicalTrials.gov number NCT03238066.

[RESULTS] Median follow-up was 64 months. Median time between previous radiation therapy and salvage brachytherapy was 77 months (range 20.4 - 244 months). Serious late toxicity was generally low. Importantly we did not register any grade ≥ 2 of late rectal toxicities. We observed Grade 3 urinary incontinence in 8/109 patients (7.3%), with further seven patients scoring urinary incontinence Grade 1 or 2 toxicity (7/109, 6.4%). All other late urogenital side effects were only grade 1 or 2: urinary retention by 8/109 (7.2%), urinary frequency 5/109 (4.6%) and urinary urgency in 2/109 patients (1.8%). The cumulative 5 years local recurrence rate (cLRR) and cumulative lymph-node recurrence rate (cLndRR) for all patients was 29% and 6.8%, respectively. Five years-biochemical disease-free survival estimates according Kaplan-Meier were 58.9%. Five years metastases-free survival, cancer specific survival and overall survival estimates according Kaplan-Meier were 77.7%, 92.7% and 85.5%, respectively.

[CONCLUSIONS] Salvage brachytherapy with interstitial hyperthermia in local recurrent, previously irradiated, prostate cancer is effective with very low late toxicity. Since there are no meaningful randomized comparative studies available, it remains unclear whether the additional use of interstitial hyperthermia can further improve the effectiveness of salvage brachytherapy alone.