A Prospective Study of High Dose-Rate Brachytherapy or Stereotactic Body Radiotherapy of Intra-Prostatic Recurrence: Toxicity and Long Term Clinical Outcome

Una Ryg; Therese Seierstad; Line Brennhaug Nilsen; Taran Paulsen Hellebust; Linda Holth Djupvik; Hilde Gustafson; Jørgen Hydal; Amar U Kishan; Knut Håkon Hole; Wolfgang Lilleby

doi:10.3389/fonc.2022.861127

A Prospective Study of High Dose-Rate Brachytherapy or Stereotactic Body Radiotherapy of Intra-Prostatic Recurrence: Toxicity and Long Term Clinical Outcome

Front Oncol. 2022 Apr 5:12:861127. doi: 10.3389/fonc.2022.861127. eCollection 2022.

Authors

Affiliations

¹ Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
² Department of Medical Physics, Oslo University Hospital, Oslo, Norway.
³ Department of Physics, University of Oslo, Oslo, Norway.
⁴ Department of Oncology, Oslo University Hospital, Oslo, Norway.
⁵ Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, United States.
⁶ Department of Urology, University of California, Los Angeles, Los Angeles, CA, United States.
⁷ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Abstract

Background: Up to half of patients with localized prostate cancer experience biochemical relapse within 10 years after definitive radiotherapy. The aim of this prospective study was to investigate the toxicity, dose to the organs at risk (OARs), and efficacy of dose-intensified focal salvage radiotherapy.

Methods and material: Thirty-three patients (median age 68.8 years) with histologically confirmed relapse after primary definitive radiotherapy were enrolled between 2012 and 2019. No patients had metastases at imaging or in bone marrow aspiration. Twenty-three patients were treated with high dose-rate brachytherapy to the recurrent tumor, defined at multiparametric MRI, with 3 fractions of 10 Gy with two weeks interval, and 10 patients by stereotactic body radiotherapy with 35 Gy to the local recurrence and 25 Gy to the whole prostate in 5 fractions. We used the RTOG-scoring system to grade genitourinary (GU) and gastrointestinal toxicity (GI) at three months (acute), and at 12, 24, and 36 months (late). Dose-volume histogram parameters to the local recurrence and the OARs were obtained and 2 Gy equivalent (EQD2) total dose was calculated using the linear-quadratic model with α/β = 3 Gy. Efficacy was assessed by the progression-free interval and overall survival.

Results: Median follow-up time was 81 months (range 21-115). The cumulative moderate to severe GI and GU toxicities were 3.0% (1/33) and 15.2% (5/33). Six patients had grade 1 acute GI toxicity, none had grade 2 or 3. One patient had grade 3 acute GU toxicity, two had grade 2, and fourteen had grade 1. One patient had late GI toxicity grade 2 and eight had grade 1. Four patients had late GU toxicity grade 2 and eight had grade 1. No patients had grade 3 late toxicity. The mean total D90 to the recurrent tumor was 77.7 ± 17.0 Gy. The mean total rectum D2cc was 17.0 ± 7.9 Gy and the mean total urethra D0.1cc was 29.1 ± 8.2 Gy. Twenty-eight patients had re-irradiation without androgen deprivation therapy (ADT). Nine of these are still relapse-free and 10 had a recurrence-free interval longer than 2 years.

Conclusion: The toxicity of salvage radiotherapy was mild to moderate. One-third of the patients achieved long-term stable disease without ADT and one-third had a recurrence-free interval longer than 2 years. Some patients progressed rapidly and probably did not benefit from re-irradiation.

Keywords: image-guided radiotherapy; prostatic neoplasms; radiation dose hypofractionation; re-irradiation; toxicity; treatment outcome.