Real-world experience with 5-aminolevulinic acid for photodynamic diagnosis of bladder cancer (2nd report): Reduced bladder recurrence after PDD-TURBT

Fukuhara, Hideo; Yamamoto, Shinkuro; Lai, Hung Wei; Karashima, Takashi; Kurabayashi, Atsushi; Furihata, Mutsuo; Inoue, Keiji

doi:10.1016/j.pdpdt.2022.102757

Cited by 18 publications

(12 citation statements)

References 20 publications

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“…Moreover, several recent systematic reviews revealed that TURBT with PDD could reduce BC recurrence and resulted in a progression risk reduction compared to conventional TURBT with WL (13)(14)(15). This retrospective study found that FL had significantly higher sensitivity and lower specificity than WL, similar to previous reports (5,16). PDD sensitivity was more than 50% higher than that of WL in diagnostic accuracy for CIS, reflecting ALA-PDD strength.…”

Section: Discussionsupporting

confidence: 86%

Poor Prognosis With Intravesical Bacillus Calmette-Guérin History After Photodynamic Diagnosis-assisted Transurethral Resection Using 5-Aminolevulinic Acid

Makino

Ofude

Kawahara

et al. 2022

In Vivo

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Background/Aim: Diagnostic efficacy and treatment outcome of orally administered 5 aminolevulinic acid (ALA) assessment for photodynamic diagnosis (PDD) in transurethral resection for non-muscle-invasive bladder cancer (NMIBC) in clinical practice. Patients and Methods: A retrospective analysis was performed of 105 patients who underwent PDD transurethral resection using orally administered ALA and were pathologically diagnosed with Ta, T1, or Tis at the Ishikawa Prefectural Central Hospital from December 2018 to May 2022. Results: Fluorescent light had a significantly higher sensitivity but a lower specificity in detecting carcinoma compared to white light (91.7% vs. 77.1%; p<0.05 and 43.0% vs. 85.2%; p<0.05, respectively), as well as in detecting carcinoma in situ lesions (80.4% vs. 28.6%; p<0.05 and 23.3% vs. 84.5%; p<0.05, respectively). The cumulative frequency of recurrence and progression 1 year after treatment were 26.3% and 12.3%, respectively. Multivariate analyses indicated that a Bacillus Calmette-Guérin (BCG) history instillation was an independent predictive factor for intravesical recurrence (hazard ratio=4.439; p=0.002) and disease progression (hazard ratio=8.534; p=0.005). The 1-year cumulative recurrence rates were 66.2% and 16.5%, respectively (p<0.001), and progression rates for patients with and without prior BCG intravesical instillation were 50.4% and 3.5%, respectively (p<0.001). Conclusion: Sufficient diagnostic accuracy and relatively good treatment outcome was shown in PDDtransurethral resection using ALA. However, prior BCG intravesical instillation for NMIBC patients was a poor prognostic factor of cancer recurrence and progression, and may be useful for clinicians in their postoperative follow-up.Transurethral resection of bladder tumor (TURBT) by intraoperative cancer detection under white light (WL) (1) is the standard therapy for non-muscle-invasive bladder cancer (NMIBC) in clinical practice, which accounts for approximately 70% of bladder cancers (BCs). However, about 50% of NMIBCs recur, and BC invades the muscle layer in the recurrence process in 15%-30% of cases (2). Therefore, improving TURBT quality and increasing the complete tumor resection rate is essential to reduce the recurrence risk. The protoporphyrin IX precursor called 5aminolevulinic acid (ALA) is attracting attention as a new generation photosensitive material for photodynamic diagnosis (PDD). PDD assisted TURBT using orally administered ALA has demonstrated clear advantages in Japan in terms of increased tumor detection and improved oncological outcome (3-7). Clinical data originating from Japan are not yet sufficient, although ALA was made available under the Japanese public medical insurance system in 2017.Recently, the Bacillus Calmette-Guérin (BCG) unresponsive disease concept was advocated; a group of diseases that recur despite adequate BCG intravesical therapy and are considered ineffective for reintroduction of BCG intravesical therapy (8, 9). However, it is unclear how prior BCG intravesical treatme...

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Section: Discussionsupporting

confidence: 86%

Poor Prognosis With Intravesical Bacillus Calmette-Guérin History After Photodynamic Diagnosis-assisted Transurethral Resection Using 5-Aminolevulinic Acid

Makino

Ofude

Kawahara

et al. 2022

In Vivo

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“…We and another research group reported that PDD assistance reduced not only the rate of the first bladder recurrence but also that of subsequent repeated bladder recurrence. In our two previous studies, 11,20 the person‐time method with 10 000 person‐follow‐up days revealed a 63% reduction of recurrence, from 10.5 (WL‐TURBT) to 3.9 (PDD‐TURBT) and a 65% reduction, from 12.8 to 5.8. Similar result was observed in this large‐scale study (Table 1).…”

Section: Discussionmentioning

confidence: 77%

“…The beneficial effect of PDD-TURBT on the BC recurrence rate in NMIBC patients has been proven in several randomized control trials (RCTs), retrospective studies, and systematic reviews and meta-analyses. [4][5][6][7]11,12,[20][21][22] In contrast, evidence regarding the positive effect of this treatment on c-progression and related mortality is limited.…”

Section: Discussionmentioning

confidence: 99%

“…The beneficial effect of PDD‐TURBT on the BC recurrence rate in NMIBC patients has been proven in several randomized control trials (RCTs), retrospective studies, and systematic reviews and meta‐analyses. 4 , 5 , 6 , 7 , 11 , 12 , 20 , 21 , 22 In contrast, evidence regarding the positive effect of this treatment on c‐progression and related mortality is limited. One RCT demonstrated a reduction in both bladder recurrence and c‐progression risk with PDD‐TURBT as compared to with WL‐TURBT (HR 0.56, 95% CI 0.39–0.80, P = 0.001 and HR 0.33, 95% CI 0.12–0.91, P = 0.031, respectively), whereas the OS and cancer‐specific survival rates remained similar.…”

Section: Discussionmentioning

confidence: 99%

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Additional oncological benefit of photodynamic diagnosis with blue light cystoscopy in transurethral resection for primary non‐muscle‐invasive bladder cancer: A comparative study from experienced institutes

et al. 2023

Self Cite

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Objectives: The objective of this work is to evaluate the additional oncological benefit of photodynamic diagnosis (PDD) using blue-light cystoscopy in transurethral resection (TURBT) for primary non-muscle-invasive bladder cancer (NMIBC) based on the International Bladder Cancer Group (IBCG)-defined progression and the subsequent pathological pathways.Patients and Methods: We reviewed 1578 consecutive primary NMIBC patients undergoing white-light TURBT (WL-TURBT) or PDD-TURBT during 2006-2020.One-to-one propensity score-matching was performed using multivariable logistic regression to obtain balanced groups. IBCG-defined progression of NMIBC included stage-up and grade-up as well as conventional definitions such as the development of muscle-invasive BC or metastatic disease. Nine oncological endpoints were evaluated. Sankey diagrams were generated to visualize follow-up pathological pathways after the initial TURBT.Results: Comparison of event-free survival between the matched groups revealed that PDD use decreased the bladder cancer recurrence risk and IBCG-defined progression risk, whereas no significant difference was noted in conventionally defined

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“…However, the specificity of the former was lower than that of the latter (80.6% vs. 95.5%) [ 73 ]. Taken together, 5-ALA-PDD significantly improves the diagnostic accuracy of non-muscular invasive bladder cancer, especially the CIS detection rate, and improves recurrence-free survival with PDD-TURBT [ 6 , 74 , 75 , 76 , 77 ].…”

Section: 5-ala-pddmentioning

confidence: 99%

5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Imaging for Tumor Detection: Recent Advances and Challenges

Harada

Murayama

Takamatsu

et al. 2022

IJMS

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5-Aminolevulinic acid (5-ALA) is a natural amino acid and a precursor of heme and chlorophyll. Exogenously administered 5-ALA is metabolized into protoporphyrin IX (PpIX). PpIX accumulates in cancer cells because of the low activity of ferrochelatase, an enzyme that metabolizes PpIX to heme. High expression of 5-ALA influx transporters, such as peptide transporters 1/2, in cancer cells also enhances PpIX production. Because PpIX radiates red fluorescence when excited with blue/violet light, 5-ALA has been used for the visualization of various tumors. 5-ALA photodynamic diagnosis (PDD) has been shown to improve the tumor removal rate in high-grade gliomas and non-muscular invasive bladder cancers. However, 5-ALA PDD remains a challenge as a diagnostic method because tissue autofluorescence interferes with PpIX signals in cases where tumors emit only weak signals, and non-tumorous lesions, such as inflammatory sites, tend to emit PpIX fluorescence. Here, we review the current outline of 5-ALA PDD and strategies for improving its diagnostic applicability for tumor detection, focusing on optical techniques and 5-ALA metabolic pathways in both viable and necrotic tumor tissues.

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Real-world experience with 5-aminolevulinic acid for photodynamic diagnosis of bladder cancer (2nd report): Reduced bladder recurrence after PDD-TURBT

Cited by 18 publications

References 20 publications

Poor Prognosis With Intravesical Bacillus Calmette-Guérin History After Photodynamic Diagnosis-assisted Transurethral Resection Using 5-Aminolevulinic Acid

Poor Prognosis With Intravesical Bacillus Calmette-Guérin History After Photodynamic Diagnosis-assisted Transurethral Resection Using 5-Aminolevulinic Acid

Additional oncological benefit of photodynamic diagnosis with blue light cystoscopy in transurethral resection for primary non‐muscle‐invasive bladder cancer: A comparative study from experienced institutes

5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Imaging for Tumor Detection: Recent Advances and Challenges

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