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

• Published in: International journal of radiation oncology, biology, physics Vol. 113; no. 2; pp. 290 - 301
• Main Authors: Hannan, Raquibul, Salamekh, Samer, Desai, Neil B., Garant, Aurelie, Folkert, Michael R., Costa, Daniel N., Mannala, Samantha, Ahn, Chul, Mohamad, Osama, Laine, Aaron, Kim, Dong W. Nathan, Dickinson, Tamara, Raj, Ganesh V., Shah, Rajal B., Wang, Jing, Jia, Xun, Choy, Hak, Roehrborn, Claus G., Lotan, Yair, Timmerman, Robert D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2022
• Subjects: Androgen Antagonists; Dose Fractionation, Radiation; HEALTH HAZARDS; Humans; Magnetic Resonance Imaging; Male; NEOPLASMS; NMR IMAGING; PATIENTS; Prospective Studies; PROSTATE; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - pathology; Prostatic Neoplasms - radiotherapy; RADIATION DOSES; RADIOLOGY AND NUCLEAR MEDICINE; Radiotherapy, Intensity-Modulated; SAFETY
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2021.10.137

Radiation dose intensification improves outcome in men with high-risk prostate cancer (HR-PCa). A prospective trial was conducted to determine safety, feasibility, and maximal tolerated dose of multilevel magnetic resonance imaging (MRI)-based 5-fraction SABR in patients with HR-PCa.
This phase I clinical trial enrolled patients with HR-PCa with grade group ≥4, prostate-specific antigen (PSA) ≥20 ng/mL, or radiographic ≥T3, and well-defined prostatic lesions on multiparametric MRI (mpMRI) into 4 dose-escalation cohorts. The initial cohort received 47.5 Gy to the prostate, 50 Gy to mpMRI-defined intraprostatic lesion(s), and 22.5 Gy to pelvic lymph nodes in 5 fractions. Radiation doses were escalated for pelvic nodes to 25 Gy and mpMRI lesion(s) to 52.5 Gy and then 55 Gy. Escalation was performed sequentially according to rule-based trial design with 7 to 15 patients per cohort and a 90-day observation period. All men received peri-rectal hydrogel spacer, intraprostatic fiducial placement, and 2 years of androgen deprivation. The primary endpoint was maximal tolerated dose according to a 90-day acute dose-limiting toxicity (DLT) rate <33%. DLT was defined as National Cancer Institute Common Toxicity Criteria for Adverse Events ≥grade 3 treatment-related toxicity. Secondary outcomes included acute and delayed gastrointestinal (GI)/genitourinary (GU) toxicity graded with Common Toxicity Criteria for Adverse Events.
Fifty-five of the 62 enrolled patients were included in the analysis. Dose was escalated through all 4 cohorts without observing any DLTs. Median overall follow-up was 18 months, with a median follow-up of 42, 24, 12, and 7.5 months for cohorts 1 to 4 respectively. Acute and late grade 2 GU toxicities were 25% and 20%, while GI were 13% and 7%, respectively. Late grade 3 GU and GI toxicities were 2% and 0%, respectively.
SABR dose for HR-PCa was safely escalated with multilevel dose painting of 47.5 Gy to prostate, 55 Gy to mpMRI-defined intraprostatic lesions, and 25 Gy to pelvic nodal region in 5 fractions. Longer and ongoing follow-up will be required to assess late toxicity.