Robotic stereotactic body radiotherapy for localized prostate cancer: final analysis of the German HYPOSTAT trial

Abstract

Purpose: We report results of the first German prospective multicenter single-arm phase II trial (ARO 2013-06; NCT02635256) of hypofractionated robotic stereotactic body radiotherapy (SBRT) for patients with localized prostate cancer (HYPOSTAT).

Methods: Patients eligible for the HYPOSTAT study had localized prostate cancer (cT1‑3 cN0 cM0), Gleason score ≤ 7, prostate-specific antigen (PSA) ≤ 15 ng/ml, prostate volume ≤ 80 cm³, and an International Prostate Symptom Score (IPSS) ≤ 12. Initially, inclusion was limited to patients ≥ 75 years or patients 70-74 years with additional risk factors. The trial protocol was later amended to allow for enrolment of patients aged ≥ 60 years. The treatment consisted of 35 Gy delivered in 5 fractions to the prostate and for intermediate- or high-risk patients, also to the proximal seminal vesicles using the CyberKnife system (Accuray Inc., Sunnyvale, CA, USA). Primary endpoint was the rate of treatment-related gastrointestinal or genitourinary grade ≥ 2 toxicity based on the RTOG scale 12-15 months after treatment. Secondary endpoints were acute toxicity, late toxicity, urinary function, quality of life, and PSA response.

Results: From July 2016 through December 2018, 85 eligible patients were enrolled and received treatment, of whom 83 could be evaluated regarding the primary endpoint. Patients mostly had intermediate-risk disease with a median PSA value of 7.97 ng/ml and Gleason score of 7a and 7b in 43.5% and 25.9% of patients, respectively. At the final follow-up 12-15 months after treatment, no patient suffered from treatment-related gastrointestinal or genitourinary grade ≥ 2 toxicity. Acute toxicity was mostly mild, with three grade 3 events, and the cumulative rate of grade ≥ 2 genitourinary toxicity was 8.4% (95% CI 4.1-16.4%). There were no major changes in urinary function or quality of life. The median PSA value dropped to 1.18 ng/ml 12-15 months after treatment. There was one patient who developed distant metastases.

Conclusion: Robotic SBRT with 35 Gy in 5 fractions was associated with a favorable short-term toxicity profile. Recruitment for the HYPOSTAT‑2 trial (ARO-2018‑4; NCT03795337), which further analyses the late toxicity of this regimen with a planned sample size of 500 patients, is ongoing.

Keywords: Biochemical recurrence; CyberKnife; Hypofractionation; Quality of life; Radiation Oncology; Toxicity.

Fig. 1

CONSORT diagram

Fig. 2

Cumulative grade ≥ 2 genitourinary toxicity in the full analysis population. Patients with a study end are censored at the respective time point. 95% confidence intervals are provided (grey shading)

Fig. 3

Prostate-specific antigen (PSA) kinetics during the study in the full analysis set. Mean values (dashed line) and standard deviations (whiskers) are shown