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Non Muscle Invasive Bladder Cancer Treatment

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Nmibc Biomarkers And Clinical Impact

EAU Reading Non-Muscle-Invasive Bladder Cancer (TaT1 and Carsinoma In Situ/CIS)

To date, existing non-invasive commercial biomarkers are not embedded in routine clinical practice due to poor sensitivity, specificity and lack of evidence. Several research bodies have recognised the lack of clinically useful biomarkers for bladder cancer. Fit for purpose sample resources accessible to high-throughput omic technologies will afford the greatest opportunity to generate translational hypotheses and ensure clinical validity and utility of putative candidate markers/signatures. Robust, future-proof, longitudinal serial sample archives providing critical insights of the natural history of bladder cancer correlated with clinical detail for retrospective translational biomarker discovery are lacking.

Treatments For Bladder Cancer

If you have bladder cancer, your healthcare team will create a treatment plan just for you. It will be based on your health and specific information about the cancer. When deciding which treatments to offer for bladder cancer, your healthcare team will consider:

  • stage
  • other medical problems you have
  • what you prefer or want

Surgical And Technical Aspects Of Tumour Resection

5.10.2.1.Surgical strategy of resection

A complete resection, performed by either fractioned or en-bloc technique, is essential to achieve a goodprognosis .

  • Piecemeal resection in fractions provides goodinformation about the vertical and horizontal extent of the tumour .
  • En-bloc resection using monopolar or bipolarcurrent, Thulium-YAG or Holmium-YAG laser is feasible in selected exophytic tumours. Itprovides high-quality resected specimens with the presence of detrusor muscle in 96-100%of cases .

The technique selected is dependent on the size and location of the tumourand experience of the surgeon.

5.10.2.2.Evaluation of resection quality

The absence of detrusor muscle in the specimenis associated with a significantly higher risk of residual disease, early recurrence andtumour under-staging . The presence of detrusormuscle in the specimen is considered as the surrogate criterion of the resection qualityand is required .

It has been shown that surgical experience can improveTURB results, which supports the role of teaching programmes .Virtual training on simulators is an emerging approach . Itsrole in the teaching process still needs to be established .

5.10.2.3.Monopolar and bipolar resection

Compared to monopolar resection, bipolar resection has been introduced toreduce the risk of complications and to produce better specimens. Currently, the results remain controversial.

5.10.2.4.Office-based fulguration and laservaporisation

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Strategy Of The Procedure

The goal of TURB in TaT1 BC is to make the correct diagnosis and completelyremove all visible lesions. It is a crucial procedure in the management of BC. Transurethralresection of the bladder should be performed systematically in individual steps .

The operative steps necessary to achieve a successful TURB includeidentifying the factors required to assign disease risk , clinical stage , adequacy of the resection , and presence of complications . To measure the size of thelargest tumour, one can use the end of cutting loop, which is approximately 1 cm wide as areference. The characteristics of the tumour are described as sessile, nodular, papillary orflat.

Palliative Or Supportive Care

Bladder Cancer Treatment Advancement Roundup

If your cancer is at an advanced stage and can’t be cured, your medical team should discuss how the cancer will progress and which treatments are available to ease the symptoms.

You can be referred to a palliative care team, who can provide support and practical help, including pain relief.

Page last reviewed: 01 July 2021 Next review due: 01 July 2024

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Relevance Of The International Bcg Shortage To The Aua Guidelines

The global shortages in TICE BCG that occurred in 2014 and 2019 led the AUA to recommend several management strategies to maintain high quality care for patients with NMIBC. These recommendations may supersede the guideline statements below. In particular, the BCG shortage impacts guideline statements 17, 20, and 21. The AUA Statement on the BCG Shortage is available at .

Who Can Use Bcg

BCG is a treatment for early-stage bladder cancer that has not yet invaded the muscle of the bladder wall. Called non-muscle invasive bladder cancers or in situ bladder cancers, these account for about half of all bladder cancers.

For 2021, it was estimated that about 83,730 new cases of bladder cancer would be diagnosed in the United States, and about 17,200 American bladder cancer patients would die from the disease.

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B Searching For The Evidence: Literature Search Strategies For Identification Of Relevant Studies To Answer The Key Questions

Publication Date Range

Searches will begin in January 1990, a date early enough to capture all relevant published studies of current treatments for bladder cancer.

Library searches will be updated while the draft report is posted for public comment and peer review to capture any new publications. Literature identified during the update search will be assessed by following the same process of dual review as all other studies considered for inclusion in the report. If any pertinent new literature is identified for inclusion in the report, it will be incorporated before the final submission of the report.

Literature Databases

Ovid MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Health Technology Assessment, National Health Sciences Economic Evaluation Database, and Database of Abstracts of Reviews of Effects will be searched to capture both published and grey literature. See Appendix A for the primary Ovid MEDLINE search strategy.

Scientific Information Packets

Manufacturers of currently available and FDA approved diagnostic biomarkers for diagnosis and surveillance of bladder cancer, and treatments for Non-MIBC will be invited to provide SIPs.

Hand Searching

Reference lists of included articles will also be reviewed for includable literature. Searches will also be supplemented by suggestions from the TEP.

Contacting Authors

Process for Selecting Studies

Exploration Of Patients After Haematuria Or Other Symptoms Suggestive Of Bladder Cancer

Non Muscle Invasive Bladder Cancer Market

It is generally accepted that none of the currently available tests canreplace cystoscopy. However, urinary cytology or biomarkers can be used as an adjunct tocystoscopy to detect missed tumours, particularly CIS. In this setting, sensitivity forhigh-grade tumours and specificity are particularly important.

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Health Economics Of Nmibc

NMIBC is one of the most costly cancers to manage on a per-patient basis because of its high prevalence, high recurrence rate, need for adjuvant treatments and the requirement for long-term cystoscopic surveillance. The total cost of treatment and 5-year follow-up of patients with NMIBC diagnosed in the UK has increased from £73million to £213million from 2001 to 2012 . From a patient perspective, there often are considerable anxieties about recurrences, transurethral resection and progression, requiring additional therapies with potential mortality and long-term morbidity . Transurethral resection itself is associated with reduced quality of life, including both mental and physical health domains, although these effects are usually transient. Substantial effects on health-related quality of life are most likely to come from adjuvant intravesical treatments and radical or palliative treatments for progression. The cost-effectiveness of NMIBC treatment strategies has not been widely studied.

Summary Of Evidence And Guidelines Fortransurethral Resection Of The Bladder Biopsies And Pathology Report

Summary of evidence

Transurethral resection of the bladder tumour followed by pathology investigation of the obtained specimen is an essentialstep in the management of NMIBC.

The absence of detrusor muscle in the specimen isassociated with a significantly higher risk of residual disease and tumourunder-staging .

In patients with a history of small Ta LG/G1 tumours,fulguration of small papillary recurrences on an outpatient basis is feasibleand safe.

A second TURB can detect residual tumours and tumourunder-staging, increase recurrence-free survival, improve outcomes after BCGtreatment and provide prognostic information.

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Clinicalapplication Of Histological Grading Systems

  • Two classification systems the WHO 1973 and the WHO 2004/2016, are currently availablefor routine clinical application.
  • The most important parameters, which must be considered for clinical application of anygrading system are its interobserver reproducibility and prognostic value .
  • To facilitate the clinical utilisation in daily practice, these guidelines providerecommendations for tumours classified based on both classification systems.

Table 4.2: WHO classification in 1973 and in 2004/2016

1973 WHO classification system

2004/2016 WHO classification system

Papillary urothelial neoplasm of low malignantpotential

Low-grade papillary urothelial carcinoma

High-grade papillary urothelial carcinoma

Figure 4.1: Stratification of tumoursaccording to grade in the WHO 1973 and 2004/2016 classifications *

*1973 WHO Grade 1 carcinomas have beenreassigned to papillary urothelial neoplasm of low malignant potential and low-grade carcinomas in the 2004 WHO classification, and Grade 2carcinomas to LG and high-grade carcinomas. All 1973 WHO Grade 3 carcinomashave been reassigned to HG carcinomas .

PUNLMP is a non-invasive neoplasm and thereforeconsidered stage pTa in the AJCC/UICC staging systems.

Table 4.3: WHO 2004 histological classification for flat lesions

Non-malignant lesions

Urothelial CIS is always high grade.

Transurethral Resection Of Bladder Tumour

BCG Unresponsive High

TURBT is the surgical removal of bladder tumours. This procedure is both diagnostic and therapeutic. It is diagnostic because the surgeon removes the tumour and all additional tissue necessary for examination under a microscope . TURBT is also therapeutic because complete removal of all visible tumours is the treatment for this cancer. Complete and correct TURBT is essential for good prognosis. In some cases, a second surgery is required after several weeks.

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Screening Of The Population At Risk Of Bladdercancer

The application of haematuria dipstick, followed by FGFR3, NMP22® orUroVysion tests if dipstick is positive has been reported in BC screening in high-riskpopulations . The low incidence ofBC in the general population and the short lead-time impair feasibility andcost-effectiveness . Routinescreening for BC is not recommended .

Role Of Cystectomy In Nmibc

Guideline Statement 27

27. In a patient with Ta low- or intermediate-risk disease, a clinician should not perform radical cystectomy until bladder-sparing modalities have failed.

Discussion

Low-grade, noninvasive tumors very rarely metastasize, and even large-volume, multifocal cancers can usually be managed with techniques, such as staged resection. Patients with low-grade recurrences can be successfully managed with intravesical chemotherapy 225 or BCG. 177,226,227 In addition, small, multifocal recurrences despite intravesical therapy can usually be treated effectively with office fulguration, repeat TURBT or even surveillance, in select cases. 64-67

Guideline Statement 28

28. In a high-risk patient who is fit for surgery with persistent high-grade T1 disease on repeat resection, or T1 tumors with associated CIS, LVI, or variant histologies, a clinician should consider offering initial radical cystectomy.

Discussion

Guideline Statement 29

29. In a high-risk patient with persistent or recurrent disease within one year following treatment with two induction cycles of BCG or BCG maintenance, a clinician should offer radical cystectomy.

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Summary Of Evidence And Guidelines Forfollow

Summary of evidence

The first cystoscopy after transurethral resection ofthe bladder at 3 months is an important prognostic indicator for recurrence andprogression.

Patients with intermediate-risk Ta tumours shouldhave an in-between follow-up scheme using cystoscopy.

Weak

Regular upper tract imaging is recommended for high-riskand very high-risk tumours.

Weak

Endoscopy under anaesthesia and bladder biopsiesshould be performed when office cystoscopy shows suspicious findings or ifurinary cytology is positive.

Strong

During follow-up in patients with positive cytologyand no visible tumour in the bladder, mapping biopsies or PDD-guided biopsies and investigation of extravesical locations are recommended.

Strong

In patients initially diagnosed with TaLG/G1-2bladder cancer, use ultrasound of the bladder during surveillance in casecystoscopy is not possible or refused by the patient.

Weak

Theimpact Of Second Resection On Treatment Outcomes

Barriers to Clinical Trials for Non-Muscle Invasive Bladder Cancer

A second TURB can increase recurrence-free survival , improve outcomes afterBCG treatment and provide prognostic information .

In a retrospective evaluation of a largemulti-institutional cohort of 2,451 patients with BCG-treated T1G3/HG tumours , the second resection improved RFS,progression-free survival and overall survival only in patients without detrusormuscle in the specimen of the initial resection .

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Treatment Of Bcg Unresponsive Tumours Late Bcg

Patients with BCG unresponsive disease are unlikely to respond to furtherBCG therapy RC is therefore the standard and preferred option. Currently, several bladderpreservation strategies are being investigated such as cytotoxic intravesical therapies , device assisted instillations intravesical immunotherapy , systemic immunotherapy or gene therapy .

A phase III RCT including predominantly high-risk NMIBC patients failing atleast a previous induction course of BCG, MMC combined with microwave-induced hyperthermiaprovided 35% overall DFS at 2 years as compared to 41% in the control arm . In the pre-planned sub-analysis, MMC and microwave-induced thermotherapyshowed lower response rates in CIS recurrences but higher DFS in non-CIS papillary tumours . Recently, the systemic immunotherapeutic drugpembrolizumab was granted FDA approval based on currently unpublished data . Promising data from a phase III multicentre RCT withintravesical nadofaragene firadenovec were published recently showing a complete response in53.4% in patients with BCG-unresponsive CIS .

At the present time, treatments other than RC are considered oncologicallyinferior in patients with BCG unresponsive disease . Various studies suggestthat repeat-BCG therapy is appropriate for non-high-grade and even for some high-graderecurrent tumours namely those relapsing beyond one year after BCG exposure .

What To Expect During Bcg Treatment

First, make sure you havent had any fluids for four hours before the treatment. Right before you go into the treatment room your doctor or nurse will have you empty your bladder.

Youll lie on your back, and the medical professional will insert a catheter into your urethra and into your bladder, likely using some local numbing, and use this tube to infuse the treatment.

Once the treatment is infused, your doctor or nurse will remove the catheter. Theyll have you lie on your back, each side, and your stomach for 15 minutes each. The BCG mycobacteria needs to touch the bladder cancer cells to activate the immune system. Youll then be free to go but will need to hold off on peeing for another hour.

Verywell / Alex Dos Diaz

For at least six hours after your infusion, youll need to disinfect your pee to ensure none of the mycobacteria spread to anyone else. Pour an equal amount of bleach into the toilet after you pee and let it sit for 15 minutes before flushing.

Also, people with a penis who undergo BCG treatment should avoid sex for 48 hours to ensure they dont pass the mycobacteria to their partners.

You will likely need multiple BCG treatments. They may be given weekly for a few weeks, then less often for months or years to prevent cancer from coming back.

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Treating Stage I Bladder Cancer

Stage I bladder cancers have grown into the connective tissue layer of the bladder wall , but have not reached the muscle layer.

Transurethral resection with fulguration is usually the first treatment for these cancers. But it’s done to help determine the extent of the cancer rather than to try to cure it. If no other treatment is given, many people will later get a new bladder cancer, which often will be more advanced. This is more likely to happen if the first cancer is high-grade .

Even if the cancer is found to be low grade , a second TURBT is often recommended several weeks later. If the doctor then feels that all of the cancer has been removed, intravesical BCG or intravesical chemo is usually given. If all of the cancer wasn’t removed, options are intravesical BCG or cystectomy .

If the cancer is high grade, if many tumors are present, or if the tumor is very large when it’s first found, radical cystectomy may be recommended.

For people who arent healthy enough for a cystectomy, radiation therapy might be an option, but the chances for cure are not as good.

Types Of Adjuvant Therapy

Any new treatment/medication is being developed ?

Adjuvant treatment is any agent administered after complete TURBT aimed at reducing the risks of NMIBC recurrence and progression. Traditionally, only intravesical agents have been used in this setting, but emerging data on the use of systemic checkpoint inhibitor immunotherapies either as a monotherapy or combined with intravesical agents may radically change this treatment paradigm. Current adjuvant intravesical treatments can be defined by the timing and sequence of their administration: perioperatively, usually within 24h of TURBT, induction, as an initial course for that particular agent, or maintenance, subsequent courses in the setting of no evidence of disease after TURBT and induction treatment.

Standard intravesical therapies can also be categorized as either chemotherapy or immunotherapy agents. The most used contemporary chemotherapy agents are mitomycin C, gemcitabine, epirubicin, and docetaxel. These are given individually or in combination depending on the indication. Historically, agents such as doxorubicin, valrubicin, cisplatin, and thiotepa, among others, were also frequently studied and used. The gold standard intravesical immunotherapy is BCG, an attenuated mycobacterium strain first described for use in bladder cancer in 1976. Interferon has also been studied, but contemporary use is limited.

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Treatment Of Bladder Cancer By Stage

Most of the time, treatment of bladder cancer is based on the tumors clinical stage when it’s first diagnosed. This includes how deep it’s thought to have grown into the bladder wall and whether it has spread beyond the bladder. Other factors, such as the size of the tumor, how fast the cancer cells are growing , and a persons overall health and preferences, also affect treatment options.

The Prognosis For Non

Non-muscle invasive bladder cancer can be treated effectively in many people, and it is quite rare for people to die from this type of bladder cancer after they have gone through treatment.1

However, it is not uncommon for this type of bladder cancer to recur later in a personâs life. This is why it is important to maintain regular check-ups after treatment. If this type of bladder cancer does recur, it usually occurs in the same place .

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