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Semelhante a Bladder cancer Dr abeer Elsayed
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Bladder cancer Dr abeer Elsayed
- 1. Bladder Cancer By Dr.Abeer Elsayed Aly Associate prof. of Medical Oncology and hematological malignancies South Egypt Cancer Institute 07/02/2017 Medical Oncology and hematological malignancy department South Egypt Cancer Institute Asuit Egypt
- 2. Bladder Cancer Demographics • Estimated Worldwide Annual Incidence: – 261,000 new cases – 115,000 deaths • Peak incidence in the 7th decade • Male to Female ratio of 3:1
- 3. Bladder Cancer Histology (worldwide) • 90%-95% transitional cell carcinoma (TCC) • 3%-7% squamous, • 1%-2% adenocarcinoma, • Other less common histologies are small cell, carcinosarcoma and sarcoma
- 4. Nonurothelial bladder tumor • Small cell carcinoma . (must evaluate for SCC of the lung or prostate) poor prognosis. • Carcinosarcoma. –contains malignant mesenchymal and epithelial elements –poor prognosis even with cystectomy, rads and/or chemo • Metastatic Carcinoma .
- 5. Nonepithelial bladder tumours (1-5%). –neurofibroma –pheochromocytoma • partial cystectomy is treatment of choice • TURBT is contraindicated –primary lymphoma –plasmacytoma –sarcomas: angiosarcoma, hemangioma, leiomyosarcoma in adult , rhabdomyosarcoma in
- 6. Bladder Cancer Risk • Risk factors for transitional cell carcinoma: • Smoking • Arylamines,Amides and Azodyes • Water chlorination byproducts • Arsenic • Chemotherapies (Cyclophoshamide, Ifosphamide) • Chronic inflamation • Radiation
- 7. Bladder Cancer and Parasitic Schistosomiasis • S. Haematobium causes chronic inflammation which can lead to bladder cancer – 60% to 90% of cancers are Squamous Cell – 5% to 15% are adenocarcinoma – A small proportion are transitional cell carcinoma
- 9. Work up
- 13. Photodynamic Diagnosis• Improves detection of tumours – Detects approx 17% extra tumours over WL alone1. – CIS: PPD detection 91-97%, WL alone 23-68% 2. • Improves Recurrence free survival – Denzinger et.al.3 301 pts randomised to WL or PDD TURBT • Median follow up 84 months • Tumor recurrences WL: 44% PDD: 16% – Babjuk et.al.4 122 pts randomised to WL or PDD • 12wk recurrence: WL:27% PDD: 8% • 2 yr recurrence: WL: 72% PDD:60% • QoL or Economic impact unproven • Possible roles – Resection of all new tumours, – Follow-up of CIS – Positive UC, but negative CE White Blue Tumour 1 . Stenzl et.al EAU 2009, 2 . Bunce et.al. BJUI 2010 105, supp 2: 2 3. Denzinger et.al. Urology 2007; 69:675 4. Babjuk et.al BJUI 2005;96:798
- 14. •TNM STAGING
- 16. Ta Papillary, epithelium confined Ti Flat carcinoma in situ T1 Lamina propria invasion T2a Superficial muscularis propria invasion T2b Deep muscularis propria invasion T3a Microscopic extension into perivesical fat T3b Macroscopic extension into perivesical fat T4a Cancer invading pelvic viscera (e.g., prostatic stroma, vaginal wall, rectum, uterus) T4b Extension to pelvic or abdominal walls, or bony pelvis
- 20. Superficial Bladder Cancer • 70% of bladder tumors present as superficial lesions • 10-20% of these progress to muscle-invasive lesions • 70% of superficial lesions present as Ta • 20% of superficial lesions present as T1 • 10% of superficial lesions present as CIS
- 21. Ta • Stage Ta tumors are usually low grade. • Only 6.9% are high grade. • Recurrence is common---- Progression is rare. • Their most important risk factor for progression is grade, not stage. • So, high-grade Ta tumors should be followed as high risk.
- 22. CIS. • Poorly differentiated, flat, urothelial carcinoma confined to the urothelium (no invasion of lamina propria). • It is NOT “premalignant”.…it is highly malignant. Urine cytology: positive in 80% to 90%. • Cystoscopically: velvety patch of erythematous mucosa, or quite often invisible. 40% to 83% progress to muscle-invasive. • Present in 20% to 75% of high-grade muscle- invasive cancers.
- 23. T1 • T1 tumors are usually papillary. • Nodular or sessile appearance suggests deeper invasion. • Increases the risk of recurrence and progression. • Lymphovascular invasion increases the risk as well.
- 24. Low Risk Patients High Risk Patients Appearance: <3 lesions <3 cm Papillary on fine stalk >3 lesions >3 cm Papillary on a thick stalk or sessile or nadular Stage: Ta T1 Carcinoma in situ , diffuse or in association with papillary tumors Grade: Well or moderately differentiated Poorly differentiated Complete resection Incomplete resection due to diffuse disease or inaccessible location Long interval between tumor recurrence Multiple superficial recurrence within short time period
- 25. Risk Tumor status Low Solitary Ta G1 intermediate Multiple TaG1 Large tumor Recurrence at 3 mo high Any high grade (incl. CIS(
- 28. Goals of Treatment • Eradicating existing disease • Preventing tumor recurrence • Preventing tumor progression
- 29. Initial management is complete transurethral resection of bladder tumor (TURBT(.
- 30. Immunotherapy • Bacille Calmette Guerin. Attenuated mycobacterium used as a vaccine for TB • Reconstituted in 50cc NS, administered 2-4 weeks post-TURBT, administer under gravity and remain for 2 hrs • Always not given perioperative.
- 31. BCG Mechanism of Action Bladder TumorBladder Tumor Cell ExpressingCell Expressing Activation MarkersActivation Markers and BCGand BCG AntigensAntigens TTHH11 IL-2IL-2 IFN-IFN-γγ TTHH00 IL-12IL-12 TNF-TNF-αα IL 12IL 12 (+((+( (+((+( ActivatedActivated MacrophageMacrophage IFN-IFN-αα ((++(( BCG CTLCTL
- 32. The Indications For BCG • primary treatment of CIS • treatment of residual papillary lesion when resection not possible(60% response) • prophylaxis for T1 and high- grade/multiple/recurrent Ta lesions (decreased recurrence by 40% vs. TUR alone) • carcinoma of the mucosa or superficial ducts of the prostate
- 33. patients after BCG should be considered for cystectomy • Those who have recurrent T1 lesion at 3 months after 6 week course of BCG • Those who have persistent Cis after 2 x 6week courses of BCG • These pts are more likely to progress to muscle invasive cancer
- 34. Interferon • Interferon as a solitary agent is more expensive and less effective than BCG or chemotherapy in eradication residual disease preventing recurrence of pappillary disease and treating CIS may be combined with BCG • some evidence for improved efficacy
- 35. Intravesical chemotherapy • Potentially destroying viable tumor cells that remain following TURBT • Preventing tumor implantation
- 36. Mitomycin C • mitomycin C. • cross-linking agent that inhibits DNA synthesis • sensitive in G1 phase, overall non-cell-cycle specific How is mitomycin C delivered • instilled weekly for 6-8 weeks at 20-60mg Doxorubicin Epirubicin Thiotepa Ethoglucid
- 37. • TUR alone < 1 immediate dose mitomycin C (within 6 hours of TUR( < mitomycin C immediate and x 5 weeks q3 month
- 38. Low risk
- 40. High risk
- 41. Follow-up involves: • History (voiding symptoms and hematuria) • Urinalysis • Urine cytology • Cystoscopy • Periodic upper tract imaging (especially for high- risk patients) • Tumor markers (investigational)
- 42. Risk Tumor status Cystoscopy Schedule Upper Tract Imaging Low Solitary Ta G1 3mo after initial resection Not necessary unless hematuria Annually beginning 9 mo after initial surveillance if no recurrence Consider cessation at 5 or more yr. Consider cytology or tumor markers intermediate Multiple TaG1 Every 3 mo for 1-2yr Consider imaging, especially for recurrence Large tumor Semiannual or annual after 2yr Imaging for hematuria Recurrence at 3 mo Consider cytology or tumor markers Restart clock with each recurrence high Any high grade (incl. CIS( Every 3 mo for 2yr Imaging annually for 2yr; then consider lengthening interval. Semiannual for 2yr Annually for lifetime Cytology at same schedule Consider tumor markers. Restart clock with each recurrence
- 43. Treatment of muscle invasive bladder cancer
- 44. Indications for radical cystectomy • Infiltrating muscle-invasive bladder cancer without evidence of metastasis or with low-volume, resectable locoregional metastases (stage T2-T3b) • Superficial bladder tumors characterized by any of the following: – Refractory to cystoscopic resection and intravesical chemotherapy or immunotherapy – Extensive disease not amenable to cystoscopic resection – Invasive prostatic urethral involvement • Stage-pT1, grade-3 tumors unresponsive to intravesical BCG vaccine therapy • CIS refractory to intravesical immunotherapy or chemotherapy • Palliation for pain, bleeding, or urinary frequency • Primary adenocarcinoma, SCC, or sarcoma
- 45. Modern Radical Cystectomy • Radical Cystectomy – Removal of bladder with surrounding fat – Prostate/seminal vesicles (males) – Uterus/fallopian tubes/ovaries/cervix (females) – + Urethrectomy • Pelvic Lymphadenectomy – More is better • Urinary Diversion – Ileal conduit – Continent cutaneous reservoir – Orthotopic neobladder
- 46. Impact of Surgical Technique on Outcomes • More extended lymph nodes dissection = better outcomes • Lower positive margin rate = better outcomes • More experienced surgeons = better outcomes
- 47. Standard LNDStandard LND ExtendedExtended LND Pelvic Lymphadenectomy
- 48. Modifications in technique • Nerve sparing for potency • Prostate sparing • Gynecologic organ sparing • Anterior vaginal wall sparing • Urethral sparing in women • Urethral sparing in men
- 51. Bladder-sparing protocol Transurthral resection Induction Therapy: Radiation + chemotherapy )cisplatin, paclitacel( Cystoscopy after 1 month no tumor tumor Consolidation: RT + CT cystectomy
- 55. Bladder Cancer Neoadjuvant Chemotherapy • Treatment of micrometastases to improveTreatment of micrometastases to improve overall survivaloverall survival • Treatment of local tumour permitting organTreatment of local tumour permitting organ preservationpreservation • Determination of chemosensitivity in vivoDetermination of chemosensitivity in vivo • More efficient & higher drug deliveryMore efficient & higher drug delivery • Problems : Progression of diseaseProblems : Progression of disease Delay in curative local therapiesDelay in curative local therapies Toxicity of chemoToxicity of chemo Accurate staging not obtainedAccurate staging not obtained
- 56. Neoadjuvant Chemotherapy in invasive bladder cancer • Meta-analysis of 2688 pts data from 10 RCTs • Platinum based combination chemo showed significant benefit in OAS • 13% reduction in death • 5% absolute benefit at 5 years (45% to 50%) • Benefit mainly in patients with p0 disease • Effect irrespective of type of local therapy • Trend towards better survival with single agent cisplat but combination significantly better than single agent cisplat (ABC Meta-analysis Collaboration Lancet 2003)
- 59. Cutaneous Ureterostomy… •One kidney drainage, with short-live prognosis •Complications (infection, stone, stenosis(
- 61. Complications of ileal conduit • Wound infection • Wound dehiscence • Urinary leakage • Ureteral obstruction • Small bowel obstruction • Ileus • Stomal gangrene • Narrowing of the stoma • Pyelonephritis • Renal calculi
- 62. Continent Urinary Diversions • Continent Ileal Urinary Reservoir Indiana Pouch • Most common continent urinary diversion • Periodically catheterized Koch Pouch Ureterosigmoidostomy • Voiding occurs from rectum
- 77. Prognostic factor for second line metastatic
- 89. Evolution of Systemic Therapy for Urothelial Cancer 2016 Today 1997 1999 2001 2003 2005 2007 2009 2011 2013 2015 Docetaxel Standard MVAC 1989 Gemcitabine + cisplatin Accelerated MVAC Paclitaxel Vinflunine Atezolizumab Cisplatin FDA approved 1978 Gemcitabine EMA approved Vinflunine EMA approved Atezolizumab FDA approved 5/18/2016 Durvalumab breakthrough therapy designation 2/17/2016 Slide credit:clinicaloptions.com Sternberg CN, Yagoda A, et al. Cancer 1989;64:2448-2458. McCaffrey JA, et al. J Clin Oncol 1997;15:1853-1857. von der Maase H, et al. J Clin Oncol 2005;23:4602-4608. Sternberg CN, et al. J Clin Oncol 2001;19:2638-2646. Vaughn DJ, et al. J Clin Oncol 2002;20:937-940. Bellmunt J, et al. J Clin Oncol 2009;27:4454-4461. Rosenberg JE, et al. Lancet. 2016;387:1909-1920. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. http://www.ema.europa.eu/ema/
- 94. Thank you
Notas do Editor
- Hematuria is the most common sign of bladder cancer, with about 80% of transitional cell carcinomas (TCCs) being diagnosed with either gross or microscopic hematuria. Otherwise, bladder cancer is usually asymptomatic. Some patients, particularly those with carcinoma in situ (CIS) will have symptoms of bladder irritability, including urinary frequency, urgency, and dysuria.1 Reference 1. Amling CL. Diagnosis and management of superficial bladder cancer. Curr Probl Cancer. 2001;25:219-278.
- Urine cytology is a standard, noninvasive, tumor-specific marker test used as an adjunct to cystoscopy. Positive urine cytology is highly predictive of transitional cell carcinoma, even in patients with normal cystoscopy findings because malignant cells may appear in the urine before lesions become visible. The major role of urine cytology is in detecting high-grade tumors and carcinoma in situ, the latter of which is often difficult to visualize cystoscopically. Cytologic criteria for malignant cells include an increased nuclear to cytoplasmic ratio and prominent nucleoli. Urine cytology requires a trained cytopathologist, and even so, there is often significant variability in interpretation.
- Voided urine cytology has a sensitivity of 38% to 60% and a specificity of 95% to 100%.1 Sensitivity can be improved when three voided specimens are obtained on three separate days. Urine cytology is most accurate in high-grade tumors, but has poor sensitivity in detecting low-grade tumors, the cells of which more closely resemble normal urothelium with fewer malignant cellular changes. It is therefore most helpful in diagnosis and follow-up of carcinoma in situ or high-grade T1 or Ta tumors. Use of bladder wash specimens, rather than voided urine specimens, increases the number of exfoliated cells, but is invasive and not cost-effective. Reference 1.Raitanen MP, Aine R, Rintala E, et al. Differences between local and review urinary cytology in diagnosis of bladder cancer. An interobserver multicenter analysis. Eur Urol. 2002;41:284-289. 2.Amling CL. Diagnosis and management of superficial bladder cancer. Curr Probl Cancer. 2001;25:219-278 3.Ramakumar S, Bhuiyan J, Besse JA, et al. Comparison of screening methods in the detection of bladder cancer. J Urol. 1999;161:388-394.
- Cystoscopy is the gold standard for diagnosis of bladder cancer since it allows complete visualization of the urethral and bladder mucosa. Any lesions visualized during cystoscopy are biopsied and/or resected. Resection has therapeutic value, and also allows for staging and provides pathologic information. Disadvantages of rigid cystoscopy include its invasiveness, requirement for anesthesia, and postoperative discomfort. With fiberoptic flexible instruments, outpatient cystoscopy with minimal patient discomfort using topical intraurethral anesthesia can be performed. The standard schedule for cystoscopic surveillance (ie, every 3–4 months) has not been clinically validated. Cystoscopy is 73% sensitive and 68.5% specific in diagnosing bladder cancer. Investigational studies have suggested that sensitivity can be improved to 97% with intravesical instillation of 5-aminolevulinic acid, which induces porphyrin fluorescence, prior to cystoscopy, and use of a violet light from a krypton ion laser (wavelength 406.7 nm).1 However, this is not widely available and is in the developmental stages. Reference 1. Kriegmair M, Baumgartner R, Knuchel R, Stepp H, Hofstadter F, Hofstetter A. Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence. J Urol. 1996;155:105-110.
- A number of different systems have been proposed for grading papillary tumors.1-4 This slide indicates the different grading categories suggested for each system and how they correspond with each other. The original system, developed by the World Health Organization (WHO) in 1973,1 classified tumors as grade I (those with the least anaplasia), grade III (those with the most anaplasia), or grade II (those in between). A system described by Murphy et al2 at the Armed Forces Institute of Pathology (AFIP) in 1994 classified malignant tumors as either low grade (equivalent to WHO grade I) or high grade (equivalent to WHO grades II and III). More recently, it has become obvious that many tumors diagnosed as grade I papillary carcinomas did not progress to invasion and metastases. Some subsequent revisions of the system attempted to address this by adding a category called “low malignant potential” (LMP). Under the most recent grading system, the World Health Organization/International Society of Urological Pathology (WHO/ISUP) system,3 urothelial neoplasms are grouped into the following four categories: •Urothelial papillomas: discrete papillary growth with a central fibrovascular core lined by urothelium of normalthickness and cytology; no architectural or cytologic atypia) •Papillary urothelial neoplasm of LMP: orderly arrangement of cells within papillae, with minimal architectural or nuclear atypia, irrespective of cell thickness; lesions are generally thick with enlarged nuclei; mitoses are infrequent and limited to basal layer •Papillary urothelial carcinoma, low grade: overall orderly appearance with moderately altered architectural/cytologic features; definite cytologic atypia; mitoses are infrequent, usually occur in lower half, and may be observed at any level of urothelium •Papillary urothelial carcinoma, high grade: totally disorderly appearance at low magnification; marked architectural and cytologic abnormalities; mitoses frequently seen at all levels of urothelium References Mostofi FK, Sobin LH, Torloni H. Histological typing of urinary bladder tumours. International Classification of tumours. No. 10. Geneva, Switzerland: World Health Organization; 1973. Murphy WM, Beckwith JB, Farrow GM. Tumours of the kidney, bladder, and related urinary structures. Fasicle 11. Atlas of Tumour Pathology, 3rd ed. Washington, DC: Armed Forces Institute of Pathology 1994. Epstein JI, Amin MB, Reuter VR, Mostofi FK. The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol. 1998;22:1435-1448. Mostofi FK, Davis CJ, Sesterhenn IA, Sobin LH. Histological Typing of Urinary Bladder Tumors, 2nd ed. Heidelburg, Germany: Springer Verlag; 1998.
- Treatment options for superficial bladder cancer include transurethral resection, cystectomy, laser therapy, photodynamic therapy, intravesical therapy with either chemotherapy or immunotherapies such as bacillus Calmette-Guérin (BCG) and/or interferon.
- The mechanism of action of intravesical bacillus Calmette-Guérin (BCG) plus interferon alfa in patients with bladder cancer is illustrated here. BCG antigens are taken up by macrophages and other antigen-presenting cells and presented to T cells, which stimulate a cellular immune response. The BCG-activated macrophages produce cytokines, including interleukin (IL)-12 and tumor necrosis factor alpha (TNF-). IL-12 plays a dominant role in the induction of interferon gamma (IFN-) production,1 whereas TNF- has direct antitumor activity. Activated T helper type 1 (TH1) cells produce IL-2 and IFN-, both of which have been shown to correlate with clinical response.2,3 Exogenous intravesical interferon alfa augments the production of IFN- by TH1 cells, which in turn enhances BCG antigen presentation and further amplifies the cellular immune response. Intravesical interferon alfa also upregulates human leukocyte antigen and Fas expression on the bladder cancer cells, which increases presentation of BCG antigens by tumor cells and enhances tumor cell lysis by activated CTLs.4 The end result is an effective anticancer immune response. References 1.O&apos;Donnell MA, Luo Y, Chen X, et al. Role of IL-12 in the induction and potentiation of IFN-gamma in response to bacillus Calmette-Guerin. J Immunol. 1999;163:4246-4252. 2.Kaempfer R, Gerez L, Farbstein H, et al. Prediction of response to treatment in superficial bladder carcinoma through pattern of interleukin-2 gene expression. J Clin Oncol. 1996;14:1778-1786. 3.Saint F, Patard JJ, Hoznek A, et al. Prognosis value of a Th1 urinary cytokine response following intravesical BCG treatment. J Urol. 1997;157(suppl):386. Abstract 1511. 4.Lattime EC, Gomella LG, McCue PA. Murine bladder carcinoma cells present antigen to BCG-specific CD4+ T-cells. Cancer Res. 1992;52:4286-4290.
- Surgery for bladder cancer can really be divided into 3 main components: First, the radical cystectomy which is removal of the bladder with its surrounding fat. In males that also routinely includes the prostate and seminal vesicles, and in women, the uterus, cervix, tubes, and ovaries. Depending on the stage of disease, the urethra may also need to be removed. The removal of the pelvic lymph nodes is also a critical component to the completeness of the surgical resection. And finally, the urinary diversion which typically has the most direct impact on the patient’s quality of life.
- One of the current controversies in the Urologic community is what is the optimal extent of the lymph node dissection. For a long time, the standard dissection would include only the lower pelvic nodes directly around the bladder. Several studies have recently supported a more extended dissection to include the nodes around the lower portions of the aorta and inferior vena cava.
- EMA, European Medicines Agency; MVAC, methotrexate, vinblastine, doxorubicin, and cisplatin.