MUSCLE INVASIVE BLADDER CARCINOMA - UROLOGY

About a quarter of all people with bladder cancer have cancer in the muscle wall of the bladder (muscle invasive bladder cancer, or MIBC). This has a high risk of spread and presents an immediate threat to life. In about 20 to 25 out of 100 people with MIBC who have had surgery to remove the bladder (radical cystectomy), microscopic spread to the lymph nodes is found. This is therefore likely to be the case in people with MIBC who have radical radiotherapy. Spread to the lymph nodes usually reduces the chance of cure considerably. Treatment options for people with MIBC are therefore directed at both the cancer in the bladder and at possible unsuspected spread to lymph nodes. The options considered are chemotherapy, radical cystectomy and radical radiotherapy.

1. MUSCLE INVASIVE BLADDER CARCINOMA ALI IMRAN, UROLOGY HTAA

2. Content

3. Epidemiology Upto 30% of total Bladder Ca T2, T3, and T4 tumors That penetrate the muscularis propria Are more aggressive and have a strong tendency to metastasize Bladder cancer is the 7th most commonly diagnosed cancer in males, whilst it drops to 11th when both genders are considered

4. Staging and classification system

5. Diagnostic evaluation

6. Treatment failure of NMIBC In 2015 the European Organisation for Research and Treatment of Cancer (EORTC) group presented new nomograms based on two large phase III trials with a median follow-up of 7.4 years. These showed that with one to three years of maintenance bacillus Calmette-Guerin (BCG), the risk for progression at 5 years was 19.3% for T1G3 tumours . Meta-analyses have demonstrated that BCG therapy prevents the risk of tumour recurrence and the risk of tumour progression, but so far, no significant overall- or disease-specific survival advantages have been shown, as compared to no intravesical therapy.

7. Treatment failure of NMIBC

8. Neoadjuvant therapy The standard treatment for patients with urothelial MIBC and MIBC with variant histologies is RC. However, RC only provides 5-year survival in about 50% of patients. To improve these results, cisplatin-based NAC has been used since the 1980s. More modern chemotherapeutic regimens such as cisplatin/gemcitabine have shown similar pT0/pT1 rates as methotrexate, vinblastine, adriamycin plus cisplatin in retrospective series and pooled data analyses, but have not been assessed in RCTs. There seem to be differences in the outcomes of patients treated with NAC for primary or secondary MIBC. As an alternative to the standard dose of cisplatin-based NAC with 70 mg/m2 on day 1, split-dose modifications regimens are often used with 35 mg/m2 on days 1+8 or days 1+2.

9. Pre and post-operative radiotherapy

10. Radical surgery and urinary diversion Radical cystectomy is the standard treatment for localised MIBC in most Western countries. Performance status and life expectancy influence the choice of primary management, as well as the type of urinary diversion, with cystectomy being reserved for patients with a longer life expectancy without concomitant disease and a better PS.

11. Indication of radical cystectomy (RC) 1) MIBC T2-T4a, N0-Nx, M0 2) High-risk and recurrent superficial tumours 3) BCG-resistant Tis, T1G3 4) Extensive papillary disease that cannot be controlled with TURB and intravesical therapy alone.

12. Gold standard of treatment Different approaches have been described to improve voiding and sexual function in patients undergoing RC for BC. In men, standard RC includes removal of the bladder, prostate, seminal vesicles, distal ureters, and regional LNs. In women, standard RC includes removal of the bladder, entire urethra and adjacent vagina, uterus, distal ureters, and regional LNs.

13. Radical cystectomy in men Four main types of sexual-preserving techniques have been described: 1. sparing cystectomy: part of or the whole prostate is preserved including seminal vesicles, vas deferens and neurovascular bundles. 2. Capsule sparing cystectomy: the capsule or peripheral part of the prostate is preserved with adenoma (including prostatic urethra) removed by TURP or en bloc with the bladder. Seminal vesicles, vas deferens and neurovascular bundles are also preserved. 3. Seminal sparing cystectomy: seminal vesicles, vas deferens and neurovascular bundles are preserved. 4. Nerve-sparing cystectomy: the neurovascular bundles are the only tissue left in place.

14. Radical cystectomy in women Pelvic floor disorders, sexual and voiding dysfunction in female patients are prevalent after RC. As part of the pre-operative evaluation a gynaecological history should be obtained and patients should be counselled on the potential negative impact of RC on sexual function and/or vaginal prolapse. Most importantly, a history of cervical cancer screening, abnormal vaginal bleeding and a family history of breast and/or ovarian cancer should be recorded, as well as ruling out possible pelvic organ prolapse. Equally important is screening for sexual and urinary function and prolapse post-operatively.

15. PLND - 1962, Whitmore and Marshall described a standard template for bilateral PLND with the following limits: lateral, genitofemoral nerve; medial, bladder wall; distal, inguinal ligament; proximal, common iliac artery up to where the ureter crosses the vessel; inferior, pelvic floor and hypogastric vessels on both the medial and the lateral side. Others set the proximal border of their extended PLND above the level of the aortic bifurcation or as high as the inferior mesenteric artery, a so-called superextended PLND. A “standard” lymphadenectomy is more limited, with the cephalad extent generally beginning at the level of the common iliac bifurcation

16. Leissner et al - PLND significantly improved the prognosis of patients with invasive bladder cancer in both node-negative and node-positive patients when a greater number of lymph nodes was resected Significant increase in 5-year tumour free survival from 63% to 85% in patients with tumour confined to the bladder wall ( pTis , pT1, and pT2), from 40% to 55% in pT3 tumours , and from 25% to 53% in patients with at most five positive lymph nodes removed.

17. Ideal Urinary Diversion Undisturbed body image Natural micturation Continence Safe upper urinary tract Non-refluxing Low pressure

18. Selection of type of diversion Age/ life-expectancy Comorbidities Oncological extent of disease Renal and hepatic functional status Bowel condition Patient’s preference Available expertise

19. Ileal conduit Simplest type of conduit to perform and least complications. Procedure: 10-15cm of ileum selected 10-15cm away from IC valve. Ileal continuity re-established cranial to the segment. Mesenteric window closed Ileum in isoperistaltic orientation Isolated segment flushed with warm saline until clear Left ureter brought to RLQ beneath the sigmoid mesocolon (inferior to IMA) Ureteroenteric anastomosis Distal end of ideal segment fashioned as end ileostomy in RLQ

20. Ileal conduit Advantage: short segment use limits metabolic change suitable in renal and hepatic insufficiency Use when post-op radiation is necessary Contraindications: short bowel syndrome radiation to terminal ileum Ascites

21. Ileal conduit Complications : Ileus/ IO (10%) Leakage (2%) Sepsis Stomal stenosis/ retraction/ prolapse Parastomal hernia Dermatitis

22. Bladder-sparing treatment for localised disease

23. TURB alone should only be considered as a therapeutic option for muscle-invasive disease after radical TURB, when the patient is unfit for cystectomy, or refuses open surgery, or as part of a multimodality bladder-preserving approach. Transurethral resection of bladder tumour

24. External beam radiotherapy

25. Chemotherapy A bladder-conserving strategy with TURB and systemic cisplatin-based chemotherapy has been reported several years ago and could lead to long-term survival with intact bladder in a highly selected patient population

26. Multimodality treatment (MMT) or trimodality treatment What is Trimodal Bladder preservation? Principles Complete TURBT Radiation to bladder and pelvic LN (Fractionated in divided doses) Chemotherapy

27. Which Patient is suitable for this strategy Elderly (> 75 yrs )which not fit for surgery Patients who wish to preserve the bladder Motivated to follow strict follow up and willing to undergo RC if recurrence or progression Complete TURBT No HN due to tumour No CIS

28. Adjuvant chemotherapy Adjuvant chemotherapy after RC for patients with pT3/4 and/or LN positive (N+) disease without clinically detectable metastases (M0) is still under debate.