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Bladder cancer and its surgical management Mr Charles Carey Core Surgical Trainee Learning objectives • Recognise the key presenting features and risk factors for bladder cancer • Understand the national haematuria referral guidelines • Recognise how bladder cancer appears on cystoscopy • Understand how bladder cancer is investigated following diagnosis • Understand how cancer staging and grading affects bladder cancer management • Understand the surgical options used to treat bladder cancer • Recognise some of the key post-operative complications following bladder cancer surgery Introduction • Bladder cancer is common and is associated with significant morbidity • Bladder cancer can be particularly challenging to treat • As such it has poorer outcomes than other forms of cancer • Staging and grading is key for deciding bladder cancer management • Surgery forms a key part of bladder cancer management • Certain population groups are at significantly higher risk than others Epidemiology • Bladder cancer is the UK's 11th most common cancer • Its incidence rate is around 10,500/year and it results in 5,555 deaths/year • It is more common in men than women o7th most common cancer in men and 17th most common cancer in women • Bladder cancer incidence rates have fallen by around 16% in the last 10 years oIncidence rates are predicted to continue to fall • Smoking is the biggest preventable case of bladder cancer in the UK o49% of cases are preventable Epidemiology • Bladder cancer is strongly linked with deprivation oThis link is particularly pronounced in women • Rates are higher in white ethnic groups than other groups • Bladder cancer is more likely to reoccur than other cancers o1-year recurrence rate = 15 – 61% o5-year recurrence rate = 31 – 78% • 5-year survival rate is around 78% Risk factors • Around half of all bladder cancer cases are caused by smoking oHeavy smoking oLong pack year history • Age and male gender significantly increase the risk. • Schistosomiasis – increases the risk of bladder SCC • Previous bladder XRT • Long termcatheters • Industrial exposure – rarer now in the UK Presenting features • Many cases are asymptomatic • Visible haematuria: 16.5 – 19.3% have bladder cancer (Cowan 2012) o No disease found: 52.5 – 72.2% • Non-visible haematuria: 3.7 – 4.8% have bladder cancer (Cowan 2012) o No disease found: 68.2 – 87.3% • LUTS • Retention • Weight loss/bone pain/headache/confusion Investigations • Classically occurs in haematuria clinic o Requires a 2 week wait referral to urology or acute review in hospital • All investigations should happen within 2 weeks of referral • History • Abdominal examination • Most centres employ a one-stop shop system • DRE in men and PV exam in females • Urine dip +/- MC&S • Flexible cystoscopy • CT-urogram o May be USS KUB • (Urine cystology) o 28 – 100% sensitivity Flexible cystoscopy • This is the gold standard investigation for bladder cancer • Allows for the direct visulalisation of the urethral and bladder mucosa • Also allows visualisation of some sections of the prostate • Bladder cancers appear as papillary tumours, solid tumours or red patches • May be very subtle and easy to miss • Bladder carcinoma in situ may not be possible to visualise • Narrow band imaging can help find tumours https://www.olympus-europahttps://radiologyassistant. l/abd men/bladder/bladder-cancer-vi-radsorming-the-World-of-Endoscopy.html CT-urogram • Serves to diagnose upper tract urothelial cancers • May also detect likely bladder tumours • Involves taking images at a delayed phase • This allows the contrast to pass from the blood, kidneys and into the collecting system and ureters Case 1 • A 65-year-old male patients attends haematuria clinic • He recalls having a few episodes of blood in his urine in the last month • Nil UTI symptoms and urine dip showed blood = +++, nitrites = neg, leucs = neg • His PMH includes HTN and asthma, his PS = 0 and he has a 20-pack year history • DRE reveals a smooth and mildly enlarged prostate and CT-urogram was normal • Flexible cystoscopy reveals 3 papillary lesions on the posterior wall, the right lateral wall and the anterior wall • What should happen next? TURBT • The patient should have a CT-TAP for staging and be counselled about TURBT • Patients may be given the BAUS leaflet regarding this procedure • Purposes of TURBT o Tumour resection– may be curative o Acquire tumour sample for staging andgrading • Risks include: o Dysuria (100%),infection,failure to cure (2 – 10%), bladder perforation, damage to local structures, urethral stricture, bleeding, anaesthetic risks, need for a catheter,need for addition.l surgery TURBT • Involves performing a rigid cystoscopy o Place the cystoscope through the urethral meatus and urethra. o Hold the penis vertically to aid centralisationof the lumen o Lower your hand as you enter the prostatic urethra to enter the bladder • Identify the ureteric orifices – these are your key anatomical landmarks • Perform a rigid cystoscopy, identify the tumour(s) and empty the bladder and • Load the resectoscope with the working element connected to bipolar diathermy • Resect the tumour superficially and up to the muscle layer TURBT • Surgery on the lateral bladder wall may stimulate the obturator nerve • This can lead to rapid legadduction (the obturator kick) • To mitigate this: o Perform the procedure with bipolar diathermy with a lower current o Discuss the need for paralysis at the theatre brief o Avoid over filling the bladder • It is important to read patients'clinic notes pre-op! • Ensure adequate haemostasis through cystodiathermy https://healthcare-in-europe.com/en/news/photodynamic-diagnosis-locates-the-smallest-tumours.html Intravesicle mitomycin • Mitomycin is a chemotherapy agent that can be given at the end of a TURBT • It can be given via a catheter in theatre and a bung is used to prevent it leaking out • Shown to decrease the risk of bladder cancer recurrence o Reduced 12month recurrence rate by up to 44% • Is recommended as standard practice following TURBT for new and recurrent cases • Ensures it is given quickly and in a safe environment • Used for non-muscle invasive cases/cases with unsure staging recurrence rate of recurrent superficial transitional cellon • Also given as a 6-week course after TURBT for non-muscle invasive cases Anticancer Res, 2001. 21: 765ults of a meta-analysis. Bladder cancer staging Non-muscle invasive • Carcinoma in situ (CIS) – not spread beyond the basement membrane • Ta – non-invasive beyond the innermost urothelium • T1 – invades into the lamina propria Muscle invasive • T2 – invades into the muscularis propria • T3 – invades into the tissue immediately surrounding the bladder • T4 – Invades directly into surrounding organs https://www.cxbladder.com/us/bladder-cancer/stages/ Bladder cancer staging • N0 – no LN mets • N1 – Single pelvic regional LN involvement • N2 – Multiple pelvic LN involvement • N3 – LN mets in the common iliac nodes • M0 – no distant mets • M1 – distant mets https://www.cxbladder.com/us/bladder-cancer/stages/ Tumour grading • 2 systems exist • Grades 1, 2 and 3 • Low vs high grade • All G1 cancers are low grade • All G3 cancers are high grade • G2 cancers may be either low or high grade • All carcinomas in situ are high grade Relook TURBT • Patients may require a 2nd TURBT if the risk of recurrence/incomplete resection is high • Bladder cancer is often multifocal and all tumours need resection • Recommended for: o All patientswith T1 disease o All patientswith grade 2or above grading o Incomplete resection o If no muscle is found on histology after the original procedure • Should occur within 6 weeks in low stage, high grade patients https://bladdercancercanada.org/en/staging-and-grading/ Why is this so necessary? • TURBT is not a massively effective operation... • Bladder cancer has high rates of tumour being left behind after TURBT o Local recurrence rate at 12months is 50% • Is it difficult to identify and resect all tumours • Re-look TURBT commonly leads to disease upstaging • Bladder carcinoma in situ has particularly high recurrence and progression rates o Often missed or mistaken for benign lesions o Often multifocal and may exist in or outside the bladder Leiblich A, Bryant R, McCormick R, muscle-invasive bladder cancer: A comparison of European and UK guidelines. Journal of Clinical Urology. 2018;11(2):144-148. doi:10.1177/2051415818757339 Risk stratification Post-operative management • Low risk – surveillance with flexi in 3 and 12 months • Intermediate risk – consider intravesicle BCG or mitomycin • High risk – intravesicle BCG OR radical cystectomy • Very high risk – radical cystectomy OR BCG if unfit or unwilling to have a cystectomy Intravesicle BCG • This is a form of immunotherapy – given in 6 rounds • Is a live attenuated form of M. bovis • Promotes the ability of the immune system to detect and kill cancer cells • Sylvester et al showed that it led to a 27% reduction in the relative risk of recurrence • Can lead to significant side effects, leading many to come off their course • Given after TURBT (but not too soon after) • Cannot be given with a UTI or bladder trauma https://www.saintlukeskc.org/health-library/treating-bladder-cancer-intravesical-therapy Case 2 • A 60-year-old lady presents to heamaturia clinic – performance status = 1 • Found to have a large, solid mass on the left posterolateral wall and 2 papillary tumours on the posterior wall • She undergoes a TURBT, which successfully resects the tumours and includes muscle • Her staging CT reveals no distant metastases • Her histology shows a G2 pT2b cancer • She is happy to undergo further treatment • What are her treatment options?Options for muscle invasive bladder cancer Radical Radiotherapy Palliative cystectomy care • Intravesicle treatments are not effective in muscle invasive bladder cancer • Radical cystectomy and XRT are combined with neoadjuvant chemotherapy • Neoadjuvant = before radial treatment and boosts cure rates Radical cystectomy • May be performed via the open or robotic approach • Removes tumour and surrounding organs, lymph nodes and urinary diversion • The operation in men is differentin men and women due to anatomical differences • In men: o Bladder Differs from a simple o Distal ureters cystectomy, which only o Prostate and prostatic urethra removes the bladder and creates urinary diversion o Seminal vesicles Aminoltejari K, Black PC. Radical cystectomy: a review of techniques, developments and controversies. Transl o Ejaculatory ducts Androl Urol. 2020 Dec;9(6):3073-3081. doi: 10.21037/tau.2020.03.23. PMID: 33457280; PMCID: PMC7807330. Radical cystectomy • RC in men often leads to damage to the neurovascular bundles that control erections • Nerve sparing techniques exist – shown to have equal effectiveness at preserving erections • These methods risk leaving positive tumour marginsing techniques https://www.uptodate.com/contents/radical-cystectomy#H4144827656 Radical cystectomy • In women: o Bladder o Distal ureter o Entire urethra o Regional LNs o The ovaries, fallopian tubes, uterus and anterior vagina may also be removed ▪Depends on the spread of the cancer and risk of organ involvement • Women with a FH of breastor ovarian cancer should undergo BSO https://www.uptodate.com/contents/radical-cystectomy#H4144827656 Aminoltejari K, Black PC.Radical cystectomy: a review of techniques, developments and controversies. Transl Androl Urol. 2020Dec;9(6):3073-3081.doi: 10.21037/tau.2020.03.23. PMID: 33457280; PMCID: PMC7807330. Urinary diversion options Continent urinary diversion Incontinent urinary diversion • Cutaneous ureterostomy • Continent cutaneous vs neobladder • Ileal conduit formation • Can lead to issues with water reabsorption o Uses 15cm of mid-ileum isolated on a vascular • Continent cutaneous pedicle o Forms a reservoir out of a bowel segment o The ureters are usually joined together o The ureters are anastomosed to the conduit o Requires ISC via astoma • Neobladder formation o The distal end is a spouted stoma o Intra vs extracorporeal o Creates abladder out of appendix o Stents are often placed to ensure patency o The bladder is connected to the urethra o Patients can void voluntarily o Catheter may be placed in the conduit https://www.uptodate.com/contents/radical-cystectomy#H4144827656 Complications following cystectomy • One of the longest and most complex urological operations – morbidity rate = 30% • General risks – bleeding, infection, unintentional damage, disease recurrence, AKI • Post-op ileus is common • Anastomotic leaks or strictures • Post-op collections • Stoma related o Hernia o Stenosis o Leakage o Skin irritation Enhanced recovery • Enhanced recovery after surgery (ERAS) is a pathway to optimise care • Most UK hospitals have these programs in place • Involves an MDT approach to pre, peri and post-op care • Key after major surgeries such as cystectomy • May involve dedicated ERAS teams • General principles include (but are not exclusive to): o Ensuring patientsare as fit and well educated as possible pre-op o Optimising post-op nutrition and physical activity o Optimising analgesia – may involve maximising opiate sparing options to promote bowel function o Optimising anti-emetics and fluid regimens https://muschealth.org/locations/florence-medical-center/services/eras-program Radiotherapy – a very brief note • XRT is not as effective as surgery • Can be given to patients who are notfitfor radical cystectomy • May have a palliative role – e.g. to stop bleeding Case 3 • An 88-year-old female patient attends a haematuria clinic • She had a previous diagnosis of non-muscle invasive bladder cancer • UnderwentTURBT 5 years ago– diagnosed with G1pTa bladder cancer • Has been cancer free on previous follow ups • She undergoes a flexible cystoscopy and 3 small areas of recurrence are shown • A general anaesthetic is considered high risk • What options are there for her? TULA • Transurethral laser ablation • Performed in the OP setting with a flexible cystoscopy • Effective for small, papillary, low risk recurrent tumours • Avoids the need for a GA • May be performed in multiple sittings • The laser has a haemostatic effect https://www.biolitec.com/en/press/press-releases/press-info-14032022.html Malde, S. et al. (2021) ‘728 A systematic review of the efficacy and safety of outpatient bladder tumour ablation’, British Journal of Surgery, 108(Supplement_6). doi:10.1093/bjs/znab259.935. Summary • The risk of bladder cancer is influenced by smoking, socioeconomic and demographic factors • Haematuria patients should undergo a flexible cystoscopy and CT-U within 2 weeks • Bladder cancer can be very challenging to manage • Bladder cancer has a high risk of recurrence • TURBT is an imperfect treatment method • Treatment and follow up heavily depend on staging and grading • Intravesicle therapies may reduce the risk of recurrence • T2 and above disease requires cystectomy or non-radical treatment