Phase II trial of CyberKnife SBRT and androgen deprivation therapy in unfavorable intermediate- to high-risk localized prostate cancer

PURPOSE: Stereotactic body radiation therapy (SBRT) with focal boost to the dominant intraprostatic lesion (DIL) provides a strategy to enhance outcomes in high-risk localized prostate cancer while minimizing toxicity. This study assessed late toxicity and quality of life (QOL) following CyberKnife-based SBRT with a simultaneous integrated boost in localized prostate cancer. METHODS AND MATERIALS: Patients with newly diagnosed, biopsy-proven unfavorable intermediate- to high-risk localized prostate cancer (at least one of the following: Gleason ≥ 4+3, MRI-defined T3a N0, PSA ≥ 20) with ≤2 MRI-defined DILs were enrolled. Participants received 36.25 Gy in 5 fractions with a simultaneous focal boost ≤47.5 Gy delivered using CyberKnife. All participants received androgen deprivation therapy. The current analysis reports RTOG-assessed late genitourinary (GU) and gastrointestinal (GI) toxicity, late International Prostate Symptom Score and urinary QOL, late International Index of Erectile Function 5-Questionnaire assessed sexual function, late EQ5D-5L QOL, and biochemical outcomes at 2 years. RESULTS: Between 2013 and 2023, 20 participants were enrolled with a median follow-up of 54 months (IQR, 24-108 months). The median D95 dose delivered to the DIL was 47.43 Gy. At 2 years, the cumulative rate of RTOG-assessed grade ≥2 GU and GI toxicity was 35% (95% CI, 15%-59%) and 5% (95% CI, 1%-25%), respectively. The prevalence of grade 2 GU and GI toxicity at 2 years was 0% and there was no late grade 3 GU and GI toxicity. There was no clinically significant worsening of EQ5D-5L-assessed QOL, International Prostate Symptom Score score, and urinary QOL scores at 2 years compared with baseline. There was a reduction in International Index of Erectile Function 5-Questionnaire scores for sexual function at 2 years (median 10; IQR, 5-18) from baseline (median 18; IQR, 6-22). There is one case of biochemical relapse reported to date. CONCLUSIONS: CyberKnife-based SBRT delivering 36.25 Gy to the prostate with a simultaneous integrated boost ≤47.5 Gy is well tolerated at 2 years. The cumulative rates of grade ≥2 GU and GI toxicity were 35% and 5%, respectively, consistent with other contemporary SBRT trials with and without focal boost.