Endoscopic Gold Fiducial Marker Placement into the Bladder Wall to Optimize Radiotherapy Targeting for Bladder-Preserving Management of Muscle-Invasive Bladder Cancer: Feasibility and Initial Outcomes

Background&Aim: High grade non-muscle invasive bladder cancer (NMIBC) is common in urological practice. Most of these cancers are or become refractory to intravesical immunotherapy and chemotherapy. Here we evaluated the efficacy of combined local bladder hyperthermia and intravesical mitomycin-C (MMC) instillation in patients with high-risk recurrent NMIBC. Materials and methods: Between February 2014 and December 2015, 18 patients with high risk NMIBC were enrolled. Patients were treated in an outpatient basis with 6 weekly induction sessions followed by monthly maintenance sessions with intravesical MMC in local hyperthermia with bladder wall thermo-chemotherapy (BWT) system (PelvixTT system, Elmedical Ltd., Hod Hasharon, Israel). The follow-up regimen included cystoscopy after the induction cycle and thereafter with regular intervals. Time to disease recurrence was defined as time from the first intravesical treatment to endoscopic or histological documentation of a new bladder tumour. Adverse events were recorded according to CTC 4.0 (Common Toxicity Criteria) score system. Results: Mean age was 72 (32-87) years. 10 patients had multifocal disease, 9 had CIS, 6 had recurrent disease and 2 had highly recurrent disease (> 3 recurrences in a 24 months period). 6 patients underwent previous intravesical chemotherapy with MMC. The average number of maintenance sessions per patient was 7.6. After a mean follow-up of 433 days, 15 patients (83.3%) were recurrence-free. 3 patients had tumour recurrence after a mean period of 248 days without progression. Side effects were limited to grade 1 in 2 patients and grade 2 in 1 patient. Conclusions: BWT seems to be feasible and safe in high grade NMIBC. More studies are needed to identify the subgroup of patients who may benefit more from this treatment.

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The efficacy and safety of EN BLOC resection in non-muscle-invasive bladder cancer

Urology and andrology ◽

10.20953/2307-6631-2020-1-26-39 ◽

2020 ◽

Vol 8 (1) ◽

pp. 26-39

Author(s):

E.A. Laukhtina ◽

◽

A.D. Shpikina ◽

M.S. Taratkin ◽

D.V. Enikeev ◽

...

Keyword(s):

Bladder Cancer ◽

Bladder Wall ◽

En Bloc Resection ◽

Bloc Resection ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

En Bloc ◽

Invasive Tumour ◽

Operative Complications ◽

Muscle Invasive

In surgical treatment of non-muscle-invasive bladder cancer (BC) the en bloc resection technique – removal of tumour in a single piece with the subjacent muscle (detrusor) – is becoming more widely used. The objective of this review was to assess the oncological efficacy (relapse incidence) and safety (of peri- and post-operative complications) of this technique for various tumour sizes. This systematic review was written in accordance with the PRISMA criteria. The relevant literature published over the past 20 years was chosen in two databases (Medline and Scopus) with the use of the search query “en bloc” and “bladder cancer”. We selected publications that assessed the efficacy and safety of en bloc resection of the bladder wall with non-muscle-invasive tumour, and also publications comparing the efficacy of en bloc резекции resection with that of transurethral resection (TUR) of the bladder. Based on analysis of 18 studies (1592 patients after en bloc resection), the following conclusions were made: the incidence of BC relapses after en bloc resection of the bladder wall (with non-muscle-invasive tumour) is significantly lower than after conventional TUR of the bladder; a practically 100-percent presence of muscle fibers is found in the histological tumour specimen; the frequency of peri- and post-operative complications in en bloc resection is significantly lower as compared with classical TUR; the choice of a power source does not influence the oncological outcomes, but laser en bloc resection is safer than electrical; extraction of tumours with sizes up to 2-3 cm is possible in one piece; tumours of larger diameters should be preliminary fragmented in the bladder cavity; comparison of tumours of various diameters did not reveal any statistical differences between the oncological outcomes of patients. The technique of en bloc resection of the bladder wall with non-muscle-invasive tumour is effective and safe for removal of smaller tumours (~ to 2 cm); as some authors point out, it is also effective in larger tumours but there are no literature evidence sufficient for such an. Key words: systematic review, en bloc resection, non-muscle-invasive bladder cancer

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Bladder-preserving therapy using a real-time tumor-tracking radiotherapy system for muscle-invasive bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.364 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 364-364

Author(s):

Haruka Miyata ◽

Takahiro Osawa ◽

Jun Frumido ◽

Hiroshi Kikuchi ◽

Ryuji Matsumoto ◽

...

Keyword(s):

Bladder Cancer ◽

Real Time ◽

Primary Tumor ◽

Bladder Wall ◽

Univariate Analysis ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Tumor Bed ◽

Tumor Tracking ◽

Muscle Invasive

364 Background: Bladder-preserving therapy with a real-time tumor-tracking radiotherapy system (RTRT system) has been used for muscle-invasive bladder cancer (MIBC) since 1998 in our institution. We evaluate long term outcomes of this therapy. Methods: From 1998 to 2016, 38 patients with a T2-T4N0M0 bladder cancer who were clinically inoperable or refused surgery were enrolled. Transurethral tumor resection (TUR) and 40 Gy irradiation to the whole bladder was followed by TUR of the tumor bed (1st Evaluation) and endoscopic implantation of fiducial markers in the bladder wall around the primary tumor. Then, a boost of 25 Gy was made to the primary tumor using RTRT system. Protocol TUR of the tumor bed was performed 6 months later (2nd Evaluation). Patients with adequate renal function (CCR>45ml/min) received concurrent chemoradiotherapy with nedaplatin (cisplatin analog made in Japan, 70mg/m2 intravenously, day1, day22, day50). Results: Median follow-up for surviving patients was 6 yr. 5- and 10-yr OS were 55%, 40%, and 5- and 10-yr PFS were 55% and 39%, respectively. The CR rate at 1st evaluation was 66%, in those patients 5- and 10-yr OS rates were 70% and 61%. Among the patients with non-CR at 1st evaluation, CR rate at 2nd evaluation was 31%. Local recurrence occurred in 13 patients. One of them was performed cystectomy and 9 were performed TUR and/or bladder injection therapy. 11 patients experienced distant recurrence, 2 of those was performed chemotherapy. In univariate analysis, male (OS; HR: 0.33, 95% CI: 0.12-0.92, PFS; HR:0.25, 95% CI: 0.09-0.69) and PS0-1 (OS; HR: 0.26, 95% CI: 0.09-0.79, PFS; HR: 0.29, 95% CI: 0.10-0.85) were significantly associated with good OS and PFS (shown in Table). In multivariate analysis, the both of these covariates were also significantly associated with good OS and PFS (male; OS; HR: 0.31, 95% CI: 0.11-0.88, PFS; HR: 0.21, 95% CI: 0.07-0.62, PS0-1; OS; HR: 0.25, 95% CI: 0.08-0.76, PFS; HR: 0.24, 95%CI: 0.09-0.75). Conclusions: Bladder-preserving therapy is a considerable option in patients medically unfit for or not desiring cystectomy.

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Mitofusin-2 Down-Regulation Predicts Progression of Non-Muscle Invasive Bladder Cancer

Diagnostics ◽

10.3390/diagnostics11081500 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1500

Author(s):

Antonella Cormio ◽

Gian Maria Busetto ◽

Clara Musicco ◽

Francesca Sanguedolce ◽

Beppe Calò ◽

...

Keyword(s):

Bladder Cancer ◽

Disease Progression ◽

Bladder Tumor ◽

Bladder Wall ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Mitofusin 2 ◽

Clinical Issue ◽

Expression Levels ◽

Muscle Invasive

Identification of markers predicting disease outcome is a major clinical issue for non-muscle invasive bladder cancer (NMIBC). The present study aimed to determine the role of the mitochondrial proteins Mitofusin-2 (Mfn2) and caseinolytic protease P (ClpP) in predicting the outcome of NMIBC. The study population consisted of patients scheduled for transurethral resection of bladder tumor upon the clinical diagnosis of bladder cancer (BC). Samples of the main bladder tumor and healthy-looking bladder wall from patients classified as NMIBC were tested for Mfn2 and ClpP. The expression levels of these proteins were correlated to disease recurrence, progression. Mfn2 and ClpP expression levels were significantly higher in lesional than in non-lesional tissue. Low-risk NMIBC had significantly higher Mfn2 expression levels and significantly lower ClpP expression levels than high-risk NMIBC; there were no differences in non-lesional levels of the two proteins. Lesional Mfn2 expression levels were significantly lower in patients who progressed whereas ClpP levels had no impact on any survival outcome. Multivariable analysis adjusting for the EORTC scores showed that Mfn2 downregulation was significantly associated with disease progression. In conclusion, Mfn2 and ClpP proteins were found to be overexpressed in BC as compared to non-lesional bladder tissue and Mfn2 expression predicted disease progression.

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TECHNICAL ASPECTS OF LASER EN BLOC RESECTION OF THE BLADDER TUMOR FOR NON-MUSCLE-INVASIVE BLADDER CANCER

Surgical Practice ◽

10.38181/2223-2427-2020-1-53-58 ◽

2020 ◽

pp. 53-58

Author(s):

A. A. Kamalov ◽

N. I. Sorokin ◽

A. M. Dymov ◽

D. A. Kislyakov ◽

D. M. Kamalov ◽

...

Keyword(s):

Bladder Cancer ◽

Bladder Tumor ◽

Bladder Wall ◽

En Bloc Resection ◽

Bloc Resection ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

En Bloc ◽

Scientific Publications ◽

Muscle Invasive

Abstract: In recent decades bladder cancer has become one of the most topical problems of modern healthcare due to its widespread distribution. This makes it necessary to investigate new effective methods of surgical treatment.Objective: Assessment of the effectiveness of en bloc resection of the bladder with tumor by analyzing scientific publications on this matter.Materials and methods: We have analyzed current articles related to this topic on the databases Pubmed and Google Scholar. The search was performed using the keywords «Bladder Tumor», «En bloc resection of the bladder wall», «non-muscle-invasive bladder cancer».Results: Most studies confirm the advantages of laser en bloc resection over other methods in terms of such parameters as the frequency of recurrence, macrohematuria, and the quality of morphological material.Conclusions: Laser en bloc resection of a bladder tumor without invasion of the muscle layer is a safe and effective operation that has a number of advantages over classical transurethral resection, namely: no obturator syndrome, high-quality material for pathomorphological research, low recurrence rate.

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Quantification and correction of distortion in diffusion-weighted MRI at 1.5 and 3 T in a muscle-invasive bladder cancer phantom for radiotherapy planning

British Journal of Radiology ◽

10.1259/bjr.20190710 ◽

2020 ◽

Vol 93 (1114) ◽

pp. 20190710

Author(s):

Jane Rogers ◽

Victoria Sherwood ◽

Sarah C. Wayte ◽

Jonathan A. Duffy ◽

Spyros Manolopoulos

Keyword(s):

Bladder Cancer ◽

Dose Escalation ◽

Fiducial Marker ◽

Radiotherapy Planning ◽

Invasive Bladder Cancer ◽

Residual Tumour ◽

Diffusion Weighted Mri ◽

Muscle Invasive Bladder Cancer ◽

Diffusion Weighted ◽

Muscle Invasive

Objective: Limited visibility of post-resection muscle-invasive bladder cancer (MIBC) on CT hinders radiotherapy dose escalation of the residual tumour. Diffusion-weighted MRI (DW-MRI) visualises areas of high tumour burden and is increasingly used within diagnosis and as a biomarker for cancer. DW-MRI could, therefore, facilitate dose escalation, potentially via dose-painting and/or accommodating response. However, the distortion inherent in DW-MRI could limit geometric accuracy. Therefore, this study aims to quantify DW-MRI distortion via imaging of a bladder phantom. Methods: A phantom was designed to mimic MIBC and imaged using CT, DW-MRI and T2W-MRI. Fiducial marker locations were compared across modalities and publicly available software was assessed for correction of magnetic susceptibility-related distortion. Results: Fiducial marker locations on CT and T2W-MRI agreed within 1.2 mm at 3 T and 1.8 mm at 1.5 T. The greatest discrepancy between CT and apparent diffusion coefficient (ADC) maps was 6.3 mm at 3 T, reducing to 1.8 mm when corrected for distortion. At 1.5 T, these values were 3.9 mm and 1.7 mm, respectively. Conclusions: Geometric distortion in DW-MRI of a model bladder was initially >6 mm at 3 T and >3 mm at 1.5 T; however, established correction methods reduced this to <2 mm in both cases. Advances in knowledge: A phantom designed to mimic MIBC has been produced and used to show distortion in DW-MRI can be sufficiently mitigated for incorporation into the radiotherapy pathway. Further investigation is therefore warranted to enable individually adaptive image-guided radiotherapy of MIBC based upon DW-MRI.

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BioXmark® liquid fiducial markers for image-guided radiotherapy in muscle invasive bladder cancer: a safety and performance trial

British Journal of Radiology ◽

10.1259/bjr.20200241 ◽

2020 ◽

Vol 93 (1111) ◽

pp. 20200241

Author(s):

Mischa de Ridder ◽

Lara C Gerbrandy ◽

Theo M de Reijke ◽

Karel A Hinnen ◽

Maarten C.C.M. Hulshof

Keyword(s):

Bladder Cancer ◽

Learning Curve ◽

Fiducial Marker ◽

Invasive Bladder Cancer ◽

The Novel ◽

Muscle Invasive Bladder Cancer ◽

Image Guided Radiotherapy ◽

Promising Tool ◽

And Performance ◽

Muscle Invasive

Objective: This study evaluated the performance of the novel liquid fiducial marker (BioXmark®) in IGRT for bladder cancer. Methods: 20 patients with muscle invasive bladder cancer were entered in this prospective, single center, Phase I-II study. The novel BioXmark® liquid markers were injected around the tumor using a flexible cystoscopy. Visibility and stability of the markers were evaluated on planning-CT and CBCT. Prospectively defined threshold for success was set at a visibility of 75%. Results: In total, 76 markers were implanted in 20 patients. Of those, 60 (79% 95% CI ± 9%) were visible on CT scan. Due to the learning curve of the technique, the visibility improved in the last 75% of patients (86% visibility) compared to the first 25% of patients with 58% visibility. Concerning stability of the BioXmark® marker, all visible markers after CT acquisition were still detectable at the last CBCT without displacement. In 15/20 (75%) of the patients, three or more markers were visible on CT. No BioXmark® related adverse events were reported. Conclusion: The success rate of this novel fiducial marker was 79%, which is above the prospectively defined threshold rate. A distinct learning curve of the injection of the liquid marker was seen over the study period. The marker showed sustained visibility and positional stability during treatment phases and also appears to be safe and easy to inject. Advances in knowledge: This novel liquid BioXmark® marker seems to be a very promising tool in daily-adaptive IGRT for bladder preserving chemoradiotherapy in muscle invasive bladder cancer.

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