Long-Term Outcomes of Stereotactic Body Radiotherapy (SBRT) for Intraprostatic Relapse after Definitive Radiotherapy for Prostate Cancer: Patterns of Failure and Association between Volume of Irradiation and Late Toxicity

Abstract

The aim of this retrospective study was to assess the adverse effects and outcomes of salvage re-irradiation with stereotactic body radiotherapy (sSBRT) for local recurrence of prostate cancer (PCa) after definitive radiotherapy (RT). The study was focused on the adverse effects and prognostic factors for treatment toxicity, followed by an analysis of patterns of failure and survival. Patients treated with sSBRT between 2012 and 2020 at a tertiary institution were included. The exclusion criteria were a primary or salvage radical prostatectomy or a palliative sSBRT dose. Patients with oligorecurrence were eligible if all metastatic lesions were treated locally with curative intent. The Kaplan–Meier method was used to estimate time to grade ≥ 3 toxicity, local control (LC), freedom from distant metastases (FFDM), progression-free survival (PFS), biochemical control (BC) and overall survival (OS). The differences between groups (focal vs. whole-gland sSBRT) were compared using the log-rank test. The Cox proportional hazards model was used to assess prognostic factors for the listed endpoints. A total of 56 patients with a median age of 70.9 years and a median follow-up of 38.6 months were included in the analysis. The majority of them received local sSBRT only (45; 80.4%), while the rest were simultaneously treated for oligometastases (11; 19.6%). Overall, 18 (32.1%) patients experienced any grade ≥ 3 toxicity, including 1 (6.7%) patient who received focal sSBRT, and 17 (41.5%) patients treated with whole-gland sSBRT. The Planning Target Volume (per cc; HR 1.01; 95% CI 1–1.02; p = 0.025) and use of ADT (yes vs. no; HR 0.35; 95%CI 0.13–0.93; p = 0.035) were independent prognostic factors for the risk of grade ≥ 3 toxicity. The estimated rate of grade ≥3 adverse events was significantly higher (7.1% vs. 43.8% at 2 years; p = 0.006), and there was no improvement in the LC (92.9% vs. 85.3% at 2 years; p = 0.759) in patients treated with focal sSBRT compared to whole-gland sSBRT. The 2- and 5-year LC were 87.6% and 47.9%, respectively; the 2- and 5-year FFDM were 72.7% and 42.8%, respectively; and the 2- and 5-year PFS were 67.9% and 28.7%, respectively. The primary pattern of failure was distant metastasis. The sSBRT for local recurrence of PCa after definitive RT was associated with a high risk of severe grade ≥ 3 toxicity, which significantly increased with the volume and extent of re-irradiation.

Re-irradiation to the Prostate using stereotactic body radiotherapy (SBRT) after initial definitive Radiotherapy – A systematic review and Meta-analysis of recent trials

“…There however seems to be higher reported toxicity rates for whole gland re-irradiation versus focal irradiation, especially for GI (0 - 4.7% for focal vs. 0 – 25% for whole gland). PTV size was one of the factors associated with the risk of G3+ toxicity reported by Miszczyk et al (42). However, a large retrospective analysis of the GETUG including 100 patients found no differences in toxicity depending on the treated volume (whole-prostate vs partial SBRT) or PTV (67).…”

“…Toxicity scoring was done using the RTOG/EORTC toxicity scoring system in two publications (23, 29) and the CTCAE scoring system (versions 3 to 5) in nine publications (25-28, 31, 33, 40-42). In two publications, CTCAE was used for acute toxicity while RTOG was used for late toxicity (24, 32).…”

“…Only few studies reported on factors associated with the occurrence of toxicity. Miszsczyk et al found an association with G3+ toxicity for PTV size, the extent of salvage radiotherapy (focal vs. whole prostate) and the use of ADT in the univariate analysis of which PTV size and ADT remained significant in the multivariate analysis (42). For G3+ GU toxicity, Fuller et al found a significant difference for patients receiving EBRT as first radiotherapy versus more intensive first therapies (41).…”

“…SBRT as salvage therapy for radiorecurrent prostate cancer has been used for more than 15 years (9, 10, 12). Early case series were usually done with a Cyberknife treatment machine whereas newer studies included cohorts treated with C-arm Linacs or MR Linacs (10, 12-17, 19, 22-33, 40-42, 57-63). Of the 14 studies included in this meta-analysis, only three included patients that were exclusively treated on a Cyberknife (40-42).…”

“…As for the efficacy of SBRT in the re-irradiation setting of radiorecurrent prostate cancer, the 2-year bRFS rates reported in the ten studies included in the meta-analysis range from 48% to 91% (23-25, 27, 29, 31, 32, 40-42). In the random effects model the 2-year bRFS was 72 % (95% CI 64 – 92%).…”