Extended Follow-up from the Stereotactic Body Radiotherapy for High-risk Localized Carcinoma of the Prostate (SHARP) Consortium: Updated Analysis of 440 Patients

Abstract

Background and objective

Most patients with high-risk localized prostate cancer (HRLPC) do not undergo stereotactic body radiotherapy (SBRT) in part because of the limited evidence of long-term outcomes. We report long-term efficacy and toxicity outcomes for men treated with SBRT for HRLPC.

Methods

Individual patient data from ten prospective clinical studies evaluating SBRT for HRLPC across nine institutions were pooled in the Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate consortium. The Kaplan-Meier method was used to estimate 5-yr biochemical recurrence (BCR) and distant metastasis (DM), stratified by receipt of intensified treatment (≥12 mo of androgen deprivation therapy [ADT] with extremely dose-escalated [≥8 Gy/fraction] prostate-directed SBRT). The impact of intensified treatment on BCR-free survival and DM-free survival was evaluated using multivariable Cox proportional hazards models. Late Common Terminology Criteria for Adverse Events grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity was analyzed using time-to-event models.

Key findings and limitations

In 440 patients with a median follow-up time of 60.4 mo, 5-yr BCR and DM rates were 22% (95% confidence interval [CI] = 17–26%] and 9.2% (95% CI = 6.2–12%), respectively. In the 93 patients (21%) who received intensified treatment, 5-yr BCR and DM rates were 7.4% (95% CI = 1.7–13%) and 3.7% (95% CI = 0–7.9%), respectively. Receipt of intensified therapy was associated with a significant reduction in both BCR (hazard ratio [HR] = 0.38 [95% CI = 0.20–0.74], p = 0.005) and DM (HR = 0.43 [95% CI = 0.18–0.99], p = 0.049). For the overall cohort, 5-yr rates of grade ≥2 GU and GI toxicity were 23% (95% CI = 19–27%) and 10% (95% CI = 7–13%), respectively. Limitations include heterogeneous treatment techniques and the nonrandomized nature of the study.

Conclusions and clinical implications

The safety and efficacy profile of SBRT for HRLPC remains favorable at long-term follow-up, and SBRT should be integrated into shared decision-making for treatment of HRLPC.