Bladder Cancer 2019

Roger WATSON , Consultant Urologist, Director of Urology/ GynaeOncology, Mater Hospitals Brisbane

Special interest Urological Cancer and Robotic Urological Surgery

Pathology upper and lower tract urothelial cancer

• Transitional cell carcinoma TCC – 2 different molecular subtypes

• Other primary tumours – SCC, adeno, neuroendocrine

• Rare – involvement of colon, rectum, uterus, cervix, prostate

• Metastases melanoma, breast, renal

Urothelial Cancer – Bladder and Upper Tract

• Remains the most expensive of all malignancies to treat

• High mortality with high risk/ metastatic disease

• Increasing issue with aging population – very complex multidisciplinary evaluation and management issues

• Improvements in pathological risk evaluation (high risk subtypes), perioperative surgical management and systemic therapy (all at significant cost)

Investigation of urinary bleeding

• History, examination

• Urine micro – assess protein, leucocytes, culture

• Quantify red cell count

• Urine cytology

• Imaging – ultrasound vs CT (prefer with iv contrast)

• Cystoscopy – outpatient flexible vs GA

• Urology referral, unless <40yrs with clear benign diagnosis

Role of the urologist in the bladder cancer multidisciplinary team• Diagnosis

• Endoscopic evaluation and treatment

• MDT discussion with pathological review

• Intravesical therapy

• Followup for bladder preservation low and high grade tumour

• Surgery with cystectomy

• Followup of urinary diversion

• Upper urinary tract tumour

Pathogenesis

• Cigarette exposure

• Chemical exposure

• Medication – cyclophosphamide

• Radiation – pelvic treatment – cervix, rectum, prostate

• Genetic- Lynch syndrome

Australia’s aging population and disease burden

Survivorship with Bladder Cancer in Australia

Smoking prevalence Australia – by age & sex (source ABS, 2018)

Evaluation and initial management

• History, examination, urine micro,

• Urine cytology

• Imaging – ultrasound, CT (urography), occass MRI, PET

• Cystoscopy – diagnostic flex cysto

• Cysto with TUR tumour – diagnostic for histopath and therapeutic

• Role of single dose intravesical chemotherapy

Enbloc TUR bladder tumour

Vs TUR tumour with ‘cut and spray’

Risk stratification with consideration to treatment and followup

• Early stage low risk ‘low risk’ followup

• Early stage high grade high risk options focused on bladder preservation

• Locally advanced high risk combination local and systemic treatment

• Advanced/ metastatic disease systemic treatment options with chemo and immunotherapy

Low risk urothelial bladder cancer

• Recurrence rate can vary and progression to high risk disease rare -plan monitoring with low risk protocol over 5+ years

• Recurrent low grade bladder cancer• Endoscopic treatment

• Single dose or 6 dose induction intravesical chemotherapy

• Tailored follow with flex cystoscopy

• LA outpatient cysto diathermy an option

• Rarely invasive treatment

Early stage high grade/ high risk

• Pathological stratification – high grade, early invasion, high risk path subtypes (micropapillary, nested, plasmacytoid, neuroendocrine,), failed intravesical therapy

• Accurately stage – careful cysto/TUR with relook if necessary, MRI, FDG PET, molecular subtyping

• Bladder preservation – intraves immunotherapy (BCG, interferon alpha), PDL1 agents (clinical trials)

• (early) cystectomy with urinary reconstruction and sexual preservation, usually without chemotherapy

Urinary markers- urine cytology &FISH dna hybridisation

Enhanced cystoscopy – bladder cancer

Storz Bluelight cystoscopy with intravesical Hexvix tumour highlighting

Locally advanced bladder cancer

• Muscle invasive, pelvic confined

• Accurate staging with FDG PET, recognising limitations

• Role of systemic therapy – conventionally neoadjuvant gemcitabine, cisplatin 4 cycles - trial options to include PDL1 agents (NIAGARA)

• Limited role for chemoradiation – concerns re local recurrence, monitoring, sexual and urinary function

• Cystectomy with detailed consideration of urinary diversion and sexual function

Surgery for Bladder Cancer

• WhenAt dx for high risk cancerAfter failed bladder preservation (immunotherapy, chemotherapy, radiation)

At progression if initially low risk cancer

Preparation

Counselling with urology, with MDT input, stomal therapy nurse specialist

Where, by whoPreparation diet exercise smoking ‘prehabilitation’Preop chemotherapyConsideration for diversionSexual function

Surgery for Bladder Cancer

• Removal of the (complete) bladder (and prostate)

• +/_ urethra

• +/- vaginal wall/ uterus

• Pelvic lymph node dissection

• Urinary diversion

• Rarely partial bladder removal

Technical aspects of Cystectomy

• Decisions influenced by:1) Preference of urinary diversion

2) Pathological stage

3) Potential U & PU & BN involvement

4) Potential ureteric involvement

5) Sexual function pre-surgery and expectationsFemales: potential preservation of vaginal wall with neurovascular bundles and pelvic floor support with and without uterus and ovaries

Males: potential preservation of neurovascular bundles; dissection of prostate, prostate apex and membranous urethra

Female cystectomy

Cystectomy with vaginal preservation

Contemporary urinary diversion following cystectomy for bladder cancer

• Cutaneous conduit diversion

• (orthotopic) continent urethral diversion

• Continent (catheterisable) cutaneous diversion

Choice of diversion

• Patient preference (with informed realistic expectations)

• Pathological risk incl need for adjuvant therapy

• Access to followup medical and nursing services

• Renal function

• Age

• Potential for parastomal hernia (obesity)

• Potential need for CIC and night time continence aids

Urinary diversion

• Cutaneous conduit has become the most popular diversion, based on acceptable predictable postop recovery, defined but acceptable long term outcomes

• Continent diversion has evolved through many stages with multiple technical developments and variants

• Continent cutaneous diversion has the recognised highest re-operation rate (40%)

• Orthotopic diversion has become a feasible option to be offered selectively, recognising• Issues if renal impairment

• Night time continence

• Upper tract (endoscopic) surveillance

Studer orthotopic ileal urinary reservoir

Department of Urology

Radboud University Nijmegen Medical Centre

The Netherlands

Neobladder as an option for urinary diversion (used selectively)

Sexual function following cystectomy

• Females – consideration for vaginal preservation, based on premorbid function and disease extent

• Males – plan nervesparing (erection sparing ) cystoprostatectomysimilar to prostate cancer outcomes, including posttreatment rehabilitation, usually with PDE5 agents

• Urinary diversion can have a variable, although sometimes minimal impact on sexual function

Survivorship with Bladder Cancer

• Life After Bladder Cancer Surgery• Physical activity, travel

• Sexual function

• Urinary stoma issues

• Cancer followup and survivorship

• Patient and Family support networks

Role of Adjuvant Chemotherapy

• Neoadjuvant vs adjuvant

• MVAC vs Gem Cis vs Immunological agents (PDL1)

• Under-utilisaton• Academic 47% community 14%

• Major concern • Delay to surgical treatment (particularly non-responders)

• Over treatment in some (potential long term morbidity and cost)

• No negative impact on surgical management and outcome (although surgery can impact chemo outcome if as adjuvant treatment)

Urothelial Bladder Cancer - Developments

• Urinary Diagnostics - urine cytology with FISH

• Digital flexible cystoscopy with narrow band imaging

• Blue light cystoscopy with Hexvix (enhanced cystoscopy)

• (TUR) histopathology with immunohistochemistry for prognostication (to define the role of bladder preservation)

• Contemporary chemoradiation, incl new (expensive) drugs

• Contemporary cystectomy with Urinary diversion• ?preserving sexual function ? Type of diversion ? Use of robotics

• Cost benefit in setting of high volume unit

Summary : Bladder Cancer

Investigate ALL urinary bleeding

Precise TUR of tumour with detailed histopathological review (with immunohistochemistry and MDT case review if high risk)

• Aim for bladder (and sexual function) preservation

• Selective use of intravesical chemo and immune therapy

• Selective role for cystectomy (currently without robotics) with tailored continent or incontinent diversion

• Selective role for adjuvant (preferably neoadjuvant) systemic chemotherapy