Photodynamic Diagnosis-Assisted Transurethral Resection Using Oral 5-Aminolevulinic Acid Decreases the Risk of Repeated Recurrence in Non-Muscle-Invasive Bladder Cancer: A Cumulative Incidence Analysis by the Person-Time Method

Miyake, Makito; Nishimura, Nobutaka; Nakai, Yasushi; Fujii, Tomomi; Owari, Takuya; Morizawa, Yosuke; Gotoh, Daisuke; Anai, Satoshi; Torimoto, Kazumasa; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

doi:10.3390/diagnostics11020185

Cited by 19 publications

(22 citation statements)

References 23 publications

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“…Some studies have already described that TURBT resections using PDD are associated with improved recurrence-free survival [ 29 , 31 , 32 ]. However, differences exist between the various studies that are related to the treatment protocol (no adjuvant treatment: Miyake et al [ 32 ]) or the lack of available information about re-TURBT [ 31 ]. This complicates a direct comparison.…”

Section: Discussionmentioning

confidence: 99%

Reduced Recurrence Rates Are Associated with Photodynamic Diagnostics Compared to White Light after Extended Transurethral Resection of Bladder Tumors

Marquardt

Richterstetter

Täubert

et al. 2022

Life

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One pillar in treating non-muscle-invasive bladder cancer (NMIBC) is the complete and high-quality transurethral resection of the primary tumor (TURBT). However, even after a high-quality primary resection, the residual tumor risk is considerable, thus requiring a re-TURBT. Resections performed with the aid of a photodynamic diagnostics report improved recurrence-free survival rates and increased detection rates of carcinoma in situ (CIS). This monocentric retrospective study reports on patients treated with an extended TURBT procedure using conventional white-light cystoscopy or photodynamic diagnostics (PDD). Only patients undergoing a TURBT resection for their primary tumor were included in the statistical analysis. Recurrence-free survival and overall survival were the clinical endpoints. Mann–Whitney U tests and chi-squared tests were used for descriptive intergroup comparisons. The associations with overall survival and recurrence-free survival were determined by univariate and multivariate analyses. The test results were considered significant when p was < 0.05. In comparison to conventional white-light cystoscopy, PDD increased the detection rates of CIS (p = 0.004) and tumor multifocality (p = 0.005) and led to reduced residual tumor incidence at the primary resection site (p < 0.001). Likewise, tumor recurrence rates were reduced in the PDD cohort (p < 0.001). Patient age and the presence of residual tumor at the primary resection site were identified as independent predictors of overall survival. For recurrence-free survival, only the PDD resection method was an independent predictor (HR = 0.43; p < 0.001). In summary, we demonstrated that the utilization of PDD techniques was associated with improved detection rates of CIS and multifocal tumors and with reduced recurrence rates. The extended resection protocol allowed us to determine that PDD resections lead to a reduced residual tumor rate at the initial resection site. This residual tumor state at the resection site, determined by extended TURBT, became an independent predictor of long-term survival. On the other hand, the PDD technique was confirmed as the only independent predictor of recurrence-free survival.

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Section: Discussionmentioning

confidence: 99%

Reduced Recurrence Rates Are Associated with Photodynamic Diagnostics Compared to White Light after Extended Transurethral Resection of Bladder Tumors

Marquardt

Richterstetter

Täubert

et al. 2022

Life

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“…PDD-assisted TURBT using ALA is becoming increasingly popular in Japan, and its usefulness has been reported in several studies (3,4,6,7). 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).…”

Section: Discussionmentioning

confidence: 99%

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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“…Miyake and Nishimura [15] retrospectively analysed data from 100 patients that underwent TURBT for primary NMIBC with no subsequent repeated adjuvant treatment, 40 using WL vs. 60 PDD-assisted using 5-ALA. The goal was to compare the risk of cumulative recurrence.…”

Section: Other Recently Published Studiesmentioning

confidence: 99%

Transurethral resection of bladder cancer with or without fluorescence

Horňák

Brisuda

Babjuk

2023

Current Opinion in Urology

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Purpose of reviewTransurethral resection of bladder cancer (TURBT) is in its standard form an inherently imperfect technique. Fluorescence-guided photodynamic diagnosis (PDD) represents one way to improve the outcome by enhancing tumour detection. Fluorescence has been used in connection with bladder cancer since the 1970s, with a number of studies being published since then. However, the method is still not recommended as a standard part of TURBT mainly because of the limited level of evidence of concerned studies, questionable cost-effectiveness and even contradictory results. The review lists the latest articles covering this topic. Recent findingsSeveral recently published meta-analyses reviewed a series of randomized controlled trials (RCTs) concerning PDD assisted TURBT. Results were generally supporting the positive effect on reduction of recurrence rate. However, the mentioned meta-analyses are overlapping in terms of reviewed RCT that provide only a low level of evidence according to a recent Cochrane review. Supposed limitations of PDD (timing of the procedure, low specificity) and possible solutions are also covered.

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Photodynamic Diagnosis-Assisted Transurethral Resection Using Oral 5-Aminolevulinic Acid Decreases the Risk of Repeated Recurrence in Non-Muscle-Invasive Bladder Cancer: A Cumulative Incidence Analysis by the Person-Time Method

Cited by 19 publications

References 23 publications

Reduced Recurrence Rates Are Associated with Photodynamic Diagnostics Compared to White Light after Extended Transurethral Resection of Bladder Tumors

Reduced Recurrence Rates Are Associated with Photodynamic Diagnostics Compared to White Light after Extended Transurethral Resection of Bladder Tumors

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

Transurethral resection of bladder cancer with or without fluorescence

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