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Phase II trial of CyberKnife SBRT and androgen deprivation therapy in unfavorable intermediate- to high-risk localized prostate cancerSmall trial shows CyberKnife radiation plus hormone therapy is well tolerated for high-risk prostate cancer

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Key Takeaway
Consider CyberKnife SBRT with ADT for localized prostate cancer, noting 35% grade ≥2 GU toxicity at 2 years in this small trial.

This Phase II trial enrolled 20 patients with newly diagnosed, biopsy-proven unfavorable intermediate- to high-risk localized prostate cancer. Eligibility required at least one of the following: Gleason ≥ 4+3, MRI-defined T3a N0, or PSA ≥ 20, with ≤2 MRI-defined DILs. The intervention consisted of CyberKnife-based SBRT with a simultaneous integrated boost delivering 36.25 Gy to the prostate and a focal boost ≤47.5 Gy to DILs, combined with androgen deprivation therapy. No comparator was reported.

At 2 years, the cumulative rate of RTOG-assessed grade ≥2 genitourinary toxicity was 35% (95% CI, 15%-59%). The cumulative rate of RTOG-assessed grade ≥2 gastrointestinal toxicity was 5% (95% CI, 1%-25%). The prevalence of grade 2 genitourinary and grade 2 gastrointestinal toxicity was 0% at 2 years. No late grade 3 genitourinary or gastrointestinal toxicity was observed.

Quality of life assessments using EQ5D-5L, International Prostate Symptom Score, and urinary QOL scores showed no clinically significant worsening compared with baseline at 2 years. International Index of Erectile Function 5-Questionnaire scores for sexual function showed a reduction from baseline, with a median reduction of 10 (IQR, 5-18) from a baseline median of 18 (IQR, 6-22). One case of biochemical relapse was reported to date. The study was well tolerated at 2 years with no reported serious adverse events or discontinuations. The median follow-up was 54 months. Limitations include the small sample size and lack of a control group.

Men with high-risk prostate cancer often face tough choices about treatment. A new trial looked at a specific radiation technique called CyberKnife combined with hormone therapy. This approach targets the tumor precisely while sparing nearby healthy tissue. The study involved 20 patients with newly diagnosed unfavorable intermediate- to high-risk localized prostate cancer. These men had specific markers like a Gleason score of 4+3 or a PSA level of 20 or higher. They received a total of 36.25 Gy to the prostate with a focal boost to specific areas. They also took androgen deprivation therapy to lower hormone levels that fuel cancer growth.

After a median follow-up of 54 months, the team checked for late side effects. At two years, 35% of patients experienced grade 2 genitourinary toxicity. This means mild to moderate urinary issues like frequency or urgency. Only 5% had grade 2 gastrointestinal toxicity, such as mild bowel discomfort. No patients suffered grade 3 toxicity, which would indicate severe problems requiring hospital care. Quality of life scores for urinary function and overall health did not worsen significantly compared to the start of treatment.

Sexual function scores did drop from baseline. The median score fell from 18 to 10. This reduction is expected with this type of treatment and hormone therapy. One case of biochemical relapse was reported during the study. The team notes this is a small trial with only 20 participants. Larger studies are needed to confirm these findings. Still, the results suggest this method is well tolerated for this specific group of patients.

What this means for you:
A small trial found CyberKnife radiation plus hormone therapy was well tolerated with low severe side effects in high-risk prostate cancer patients.

Study Details

Study typePhase2
Sample sizen = 20
EvidenceLevel 3
Follow-up24.0 mo
PublishedMay 2026
View Original Abstract ↓
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.
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