SABR for High-Risk Prostate Cancer: A Prospective Multilevel MRI-Based Dose Escalation Trial.

Area of Science:

• Radiation Oncology
• Urologic Oncology
• Medical Physics

Background:

• High-risk prostate cancer (HR-PCa) outcomes improve with intensified radiation doses.
• Stereotactic ablative radiotherapy (SABR) is a promising approach for HR-PCa.
• Multilevel magnetic resonance imaging (MRI)-based dose painting allows precise radiation targeting.

Purpose of the Study:

• To determine the safety, feasibility, and maximal tolerated dose (MTD) of a 5-fraction MRI-based SABR regimen in patients with HR-PCa.
• To establish dose-escalation limits for prostate, intraprostatic lesions, and pelvic lymph nodes.
• To evaluate acute and delayed toxicities associated with escalated SABR doses.

Main Methods:

• A prospective phase I dose-escalation trial enrolled patients with HR-PCa.
• Patients were assigned to 4 dose-escalation cohorts, receiving escalating doses of SABR.
• Dose-limiting toxicity (DLT) was assessed within 90 days, defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) grade ≥3.
• All patients received a hydrogel spacer, fiducial markers, and androgen deprivation therapy.

Main Results:

• Dose escalation was successfully completed across all 4 cohorts without reaching the MTD.
• Fifty-five patients were analyzed, with a median follow-up of 18 months.
• Acute and late grade 2 genitourinary (GU) toxicities were observed in 25% and 20% of patients, respectively.
• Acute and late grade 2 gastrointestinal (GI) toxicities were observed in 13% and 7% of patients, respectively.
• No late grade 3 GU or GI toxicities were reported.

Conclusions:

• Multilevel MRI-based SABR for HR-PCa can be safely escalated to doses of 47.5 Gy to the prostate, 55 Gy to intraprostatic lesions, and 25 Gy to pelvic nodes in 5 fractions.
• This dose escalation demonstrated an acceptable toxicity profile.
• Further follow-up is necessary to fully assess long-term toxicity and efficacy.