Stereotactic Body Radiotherapy for High-Risk Prostate Cancer: A Systematic Review

Background: Radiotherapy (RT) is an established, potentially curative treatment option for all risk constellations of localized prostate cancer (PCA). Androgen deprivation therapy (ADT) and dose-escalated RT can further improve outcome in high-risk (HR) PCA. In recent years, shorter RT schedules based on hypofractionated RT have shown equal outcome. Stereotactic body radiotherapy (SBRT) is a highly conformal RT technique enabling ultra-hypofractionation which has been shown to be safe and efficient in patients with low- and intermediate-risk PCA. There is a paucity of data on the role of SBRT in HR PCA. In particular, the need for pelvic elective nodal irradiation (ENI) needs to be addressed. Therefore, we conducted a systematic review to analyze the available data on observed toxicities, ADT prescription practice, and oncological outcome to shed more light on the value of SBRT in HR PCA.

Methods: We searched the PubMed and Embase electronic databases for the terms "prostate cancer" AND "stereotactic" AND "radiotherapy" in June 2020. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations.

Results: After a rigorous selection process, we identified 18 individual studies meeting all selection criteria for further analyses. Five additional studies were included because their content was judged as relevant. Three trials have reported on prostate SBRT including pelvic nodes; 2 with ENI and 1 with positive pelvic nodes only. The remaining studies investigated SBRT of the prostate only. Grade 2+ acute genitourinary (GU) toxicity was between 12% and 46.7% in the studies investigating pelvic nodes irradiation and ranged from 0% to 89% in the prostate only studies. Grade 2+ chronic GU toxicity was between 7% and 60% vs. 2% and 56.7%. Acute gastrointestinal (GI) grade 2+ toxicity was between 0% to 4% and 0% to 18% for studies with and without pelvic nodes irradiation, respectively. Chronic GI grade 2+ toxicity rates were between 4% and 50.1% vs. 0% and 40%. SBRT of prostate and positive pelvic nodes only showed similar toxicity rates as SBRT for the prostate only. Among the trials that reported on ADT use, the majority of HR PCA patients underwent ADT for at least 2 months; mostly neoadjuvant and concurrent. Biochemical control rates ranged from 82% to 100% after 2 years and 56% to 100% after 3 years. Only a few studies reported longer follow-up data.

Conclusion: At this point, SBRT with or without pelvic ENI cannot be considered the standard of care in HR PCA, due to missing level 1 evidence. Treatment may be offered to selected patients at specialized centers with access to high-precision RT. While concomitant ADT is the current standard of care, the necessary duration of ADT in combination with SBRT remains unclear. Ideally, all eligible patients should be enrolled in clinical trials.