High performance of 5‐aminolevulinic acid‐induced fluorescent selective upper tract urinary cytology

Abstract

Objectives To investigate the efficacy of selective upper tract urinary cytology using extracorporeal 5‐aminolevulinic acid for the diagnosis of upper urinary tract urothelial carcinoma. Methods We evaluated 104 patients who underwent radical nephroureterectomy and were diagnosed pathologically as having upper urinary tract urothelial carcinoma between March 2013 and May 2019 in Osaka Rosai Hospital. Preoperatively, we collected upper tract urinary cytology from both sides, and compared the sensitivity and specificity between conventional urine cytology and 5‐aminolevulinic acid‐induced fluorescent urine cytology. Results The sensitivity of 5‐aminolevulinic acid‐induced fluorescent selective upper tract urinary cytology was significantly higher than conventional cytology (90.4% vs 66.3%, P < 0.001), whereas the specificity was equally high (100% vs 98.2%, P = 1.0). In more detailed analysis, the sensitivity of 5‐aminolevulinic acid‐induced fluorescent selective upper tract urinary cytology was significantly higher than that of conventional cytology unrelated to patients’ age (<76 years: 90.2% vs 68.6%, P = 0.013; ≥76 years: 90.6% vs 64.2%, P = 0.021), sex (male: 89.2% vs 67.5%, P = 0.001; female: 95.2% vs 61.9%, P = 0.02) or pT stage (pT1 or less: 91.4% vs 69.0%, P = 0.005; pT2 or more: 89.1% vs 63.0%, P = 0.006), tumor grade (high grade: 91.0% vs 70.5%, P = 0.002; low grade: 88.5% vs 53.8%, P = 0.013), and tended to be more efficacious for tumors that could not be detected by imaging techniques (83.3% vs 50.0%, P = 0.075). Conclusions 5‐Aminolevulinic acid‐induced fluorescent selective upper tract urinary cytology is more sensitive than conventional cytology for the diagnosis of upper urinary tract urothelial carcinoma, regardless of pT stage and tumor grade.

Editorial Comment to High performance of 5‐aminolevulinic acid‐induced fluorescent selective upper tract urinary cytology

“…[3][4][5] Yamamichi et al reported the feasibility of selective upper tract urinary cytology by ALA-PDD. 6 The sensitivity and specificity of selective upper urinary cytology were statistically improved by using ALA-PDD. Tumor cells that biologically accumulated protoporphyrin IX in mitochondria show red fluorescence.…”

“…Yamamichi et al. reported the feasibility of selective upper tract urinary cytology by ALA‐PDD . The sensitivity and specificity of selective upper urinary cytology were statistically improved by using ALA‐PDD.…”

Shedding Light on Bladder Cancer Diagnosis in Urine

“…The sensitivity of ALA-induced fluorescence cytology (82%) was higher than conventional cytology (49%) in low-grade tumours and NMIB tumours. Recent studies by Yamamichi et al [69,81] compared 5-ALA guided fluorescent urine cytology to conventional cytology for bladder cancer detection in patient urine samples. They found overall sensitivity and similar specificity rates as the Fujimoto group (5-ALA vs. conventional urine cytology: sensitivity 86.9% to 90.4% vs. 66.3% to 69.4% and specificity 96.2% to 100% vs. 95.6% to 98.2% respectively).…”

Activity-Based Fluorescence Diagnostics for Cancer

“…Due to its ability to penetrate the blood brain barrier (BBB), 5-ALA has been used as a contrast probe especially for the visualization of glioma . In recent years, it has also proved effective for urological, endometrial, and gastrointestinal cancers. , 5-ALA hexyl ester, which shows enhanced PpIX production, has been utilized for the detection of bladder cancer . However, the question of whether 5-ALA is able to consistently detect all cancer cells is still under debate.…”