Feasibility and safety of intraoperative photodynamic diagnosis using 5-aminolevulinic acid in breast cancer surgery

Abstract Purpose Intraoperative margin assessment remains a clinical challenge in breast cancer surgery. We conducted a prospective pilot study to evaluate the feasibility, safety, and diagnostic performance of 5-aminolevulinic acid (5-ALA)–based photodynamic diagnosis (PDD) using a commercially available imaging system in Japan. Methods Patients with primary breast cancer scheduled for mastectomy and tumor size > 2 cm received oral 5-ALA (20 mg/kg) 2–4 hours before surgery. Excised specimens were incised immediately after resection and examined under white light and blue-light PDD. Punch biopsies were obtained from areas classified by gross inspection and PDD findings. Pathology served as the reference standard. Primary endpoints were diagnostic odds ratio (DOR) and safety; secondary endpoints included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results Ten patients received 5-ALA. PDD visualization was feasible in 6 cases when specimens were examined within 2–5 minutes after excision. A total of 33 punch biopsies were analyzed. Compared with gross inspection alone (sensitivity 84.6%, specificity 85.0%, DOR 31.2), the addition of PDD improved sensitivity to 92.3% and increased DOR to 47.9, with specificity of 80.0%. PDD identified several grossly occult tumor foci. No adverse events related to 5-ALA were observed. Conclusions In this prospective pilot study, intraoperative 5-ALA–based PDD was feasible and safe in breast cancer specimens. The addition of fluorescence information improved diagnostic performance compared with gross assessment alone. Further studies are warranted to determine its clinical utility in breast-conserving surgery.