Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
Bladder Cancer
By
Dr.Abeer Elsayed Aly
Associate prof. of Medical Oncology and hematological
malignancies
South Egypt Canc...
Bladder Cancer Demographics
• Estimated Worldwide Annual Incidence:
– 261,000 new cases
– 115,000 deaths
• Peak incidence ...
Bladder Cancer Histology (worldwide)
• 90%-95% transitional cell carcinoma (TCC)
• 3%-7% squamous,
• 1%-2% adenocarcinoma,...
Nonurothelial bladder
tumor
• Small cell carcinoma .
(must evaluate for SCC of the lung or
prostate) poor prognosis.
• Car...
Nonepithelial bladder tumours
(1-5%).
–neurofibroma
–pheochromocytoma
• partial cystectomy is treatment of choice
• TURBT ...
Bladder Cancer Risk
• Risk factors for transitional cell carcinoma:
• Smoking
• Arylamines,Amides and Azodyes
• Water chlo...
Bladder Cancer
and Parasitic Schistosomiasis
• S. Haematobium causes chronic inflammation
which can lead to bladder cancer...
Work up
Photodynamic Diagnosis• Improves detection of tumours
– Detects approx 17% extra tumours over WL alone1.
– CIS: PPD detect...
•TNM STAGING
Ta Papillary, epithelium confined
Ti Flat carcinoma in situ
T1 Lamina propria invasion
T2a Superficial muscularis propria ...
Superficial bladder cancer
Superficial Bladder Cancer
• 70% of bladder tumors present as superficial
lesions
• 10-20% of these progress to muscle-inv...
Ta
• Stage Ta tumors are usually low grade.
• Only 6.9% are high grade.
• Recurrence is common---- Progression is rare.
• ...
CIS.
• Poorly differentiated, flat, urothelial
carcinoma confined to the urothelium (no
invasion of lamina propria).
• It ...
T1
• T1 tumors are usually papillary.
• Nodular or sessile appearance suggests deeper
invasion.
• Increases the risk of re...
Low Risk Patients High Risk Patients
Appearance: <3 lesions
<3 cm
Papillary on fine stalk
>3 lesions
>3 cm
Papillary on a ...
Risk Tumor status
Low Solitary Ta G1
intermediate Multiple TaG1
Large tumor
Recurrence at 3 mo
high Any high grade (incl. ...
Goals of Treatment
• Eradicating existing disease
• Preventing tumor recurrence
• Preventing tumor progression
Initial management is complete
transurethral resection of
bladder tumor (TURBT(.
Immunotherapy
• Bacille Calmette Guerin.
Attenuated mycobacterium used as a vaccine for
TB
• Reconstituted in 50cc NS, adm...
BCG
Mechanism of Action
Bladder TumorBladder Tumor
Cell ExpressingCell Expressing
Activation MarkersActivation Markers
and...
The Indications For BCG
• primary treatment of CIS
• treatment of residual papillary lesion when
resection not possible(60...
patients after BCG should be
considered for cystectomy
• Those who have recurrent T1 lesion at 3
months after 6 week cours...
Interferon
• Interferon as a solitary agent is more
expensive and less effective than BCG or
chemotherapy in eradication r...
Intravesical chemotherapy
• Potentially destroying viable tumor
cells that remain following TURBT
• Preventing tumor impla...
Mitomycin C
• mitomycin C.
• cross-linking agent that inhibits DNA synthesis
• sensitive in G1 phase, overall non-cell-cyc...
• TUR alone < 1 immediate dose
mitomycin C (within 6 hours of
TUR( < mitomycin C immediate and
x 5 weeks q3 month
Low risk
Intermediate
risk
High risk
Follow-up involves:
• History (voiding symptoms and hematuria)
• Urinalysis
• Urine cytology
• Cystoscopy
• Periodic upper...
Risk Tumor status Cystoscopy Schedule Upper Tract Imaging
Low Solitary Ta G1 3mo after initial resection Not necessary unl...
Treatment of muscle invasive
bladder cancer
Indications for radical
cystectomy
• Infiltrating muscle-invasive bladder cancer without evidence of
metastasis or with lo...
Modern Radical Cystectomy
• Radical Cystectomy
– Removal of bladder with surrounding fat
– Prostate/seminal vesicles (male...
Impact of Surgical Technique on
Outcomes
• More extended lymph nodes dissection =
better outcomes
• Lower positive margin ...
Standard LNDStandard LND ExtendedExtended
LND
Pelvic Lymphadenectomy
Modifications in technique
• Nerve sparing for potency
• Prostate sparing
• Gynecologic organ sparing
• Anterior vaginal w...
Bladder-sparing protocol
Transurthral resection
Induction Therapy: Radiation + chemotherapy
)cisplatin, paclitacel(
Cystos...
Neoadjuvant Treatment
Bladder Cancer
Neoadjuvant Chemotherapy
• Treatment of micrometastases to improveTreatment of micrometastases to improve
o...
Neoadjuvant Chemotherapy in invasive
bladder cancer
• Meta-analysis of 2688 pts data from 10 RCTs
• Platinum based combina...
Cutaneous
Ureterostomy…
•One kidney
drainage, with
short-live prognosis
•Complications
(infection, stone,
stenosis(
Complications of ileal conduit
• Wound infection
• Wound dehiscence
• Urinary leakage
• Ureteral obstruction
• Small bowel...
Continent Urinary Diversions
• Continent Ileal Urinary Reservoir
Indiana Pouch
• Most common continent urinary
diversion
•...
Uretero-
sigmoideostom
y
Bladder reconstruction
Metastatic bladder cancer
Prognostic factor for second line
metastatic
Immune check point
inhibitors
Evolution of Systemic Therapy
for Urothelial Cancer
2016
Today
1997 1999 2001 2003 2005 2007 2009 2011 2013 2015
Docetaxel...
Thank you
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Bladder cancer Dr abeer Elsayed
Upcoming SlideShare
Loading in …5
×

Bladder cancer Dr abeer Elsayed

Treatment of bladder Cancer

  • Be the first to comment

Bladder cancer Dr abeer Elsayed

  1. 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. 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. 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. 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. 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. 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. 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
  8. 8. Work up
  9. 9. 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
  10. 10. •TNM STAGING
  11. 11. 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
  12. 12. Superficial bladder cancer
  13. 13. 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
  14. 14. 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.
  15. 15. 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.
  16. 16. 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.
  17. 17. 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
  18. 18. Risk Tumor status Low Solitary Ta G1 intermediate Multiple TaG1 Large tumor Recurrence at 3 mo high Any high grade (incl. CIS(
  19. 19. Goals of Treatment • Eradicating existing disease • Preventing tumor recurrence • Preventing tumor progression
  20. 20. Initial management is complete transurethral resection of bladder tumor (TURBT(.
  21. 21. 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.
  22. 22. 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
  23. 23. 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
  24. 24. 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
  25. 25. 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
  26. 26. Intravesical chemotherapy • Potentially destroying viable tumor cells that remain following TURBT • Preventing tumor implantation
  27. 27. 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
  28. 28. • TUR alone < 1 immediate dose mitomycin C (within 6 hours of TUR( < mitomycin C immediate and x 5 weeks q3 month
  29. 29. Low risk
  30. 30. Intermediate risk
  31. 31. High risk
  32. 32. Follow-up involves: • History (voiding symptoms and hematuria) • Urinalysis • Urine cytology • Cystoscopy • Periodic upper tract imaging (especially for high- risk patients) • Tumor markers (investigational)
  33. 33. 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
  34. 34. Treatment of muscle invasive bladder cancer
  35. 35. 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
  36. 36. 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
  37. 37. Impact of Surgical Technique on Outcomes • More extended lymph nodes dissection = better outcomes • Lower positive margin rate = better outcomes • More experienced surgeons = better outcomes
  38. 38. Standard LNDStandard LND ExtendedExtended LND Pelvic Lymphadenectomy
  39. 39. Modifications in technique • Nerve sparing for potency • Prostate sparing • Gynecologic organ sparing • Anterior vaginal wall sparing • Urethral sparing in women • Urethral sparing in men
  40. 40. Bladder-sparing protocol Transurthral resection Induction Therapy: Radiation + chemotherapy )cisplatin, paclitacel( Cystoscopy after 1 month no tumor tumor Consolidation: RT + CT cystectomy
  41. 41. Neoadjuvant Treatment
  42. 42. 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
  43. 43. 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)
  44. 44. Cutaneous Ureterostomy… •One kidney drainage, with short-live prognosis •Complications (infection, stone, stenosis(
  45. 45. 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
  46. 46. Continent Urinary Diversions • Continent Ileal Urinary Reservoir Indiana Pouch • Most common continent urinary diversion • Periodically catheterized Koch Pouch Ureterosigmoidostomy • Voiding occurs from rectum
  47. 47. Uretero- sigmoideostom y
  48. 48. Bladder reconstruction
  49. 49. Metastatic bladder cancer
  50. 50. Prognostic factor for second line metastatic
  51. 51. Immune check point inhibitors
  52. 52. 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/
  53. 53. Thank you

    Be the first to comment

    Login to see the comments

  • AbeerIbrahim4

    Jul. 1, 2017
  • AmirDar5

    Jul. 13, 2017
  • AhmedFathy167

    Nov. 2, 2017
  • DHIRESHCHOURASIYA

    Nov. 25, 2017
  • JaiJoshiMD

    Feb. 16, 2018
  • DrMohamedMahmoud

    Feb. 20, 2018
  • AdonayYohans

    Feb. 20, 2018
  • EpandeRichard

    Oct. 9, 2018
  • abdulrazaknweir

    Feb. 4, 2019
  • droutray

    Aug. 1, 2020
  • NasirIsmail13

    Mar. 23, 2021

Treatment of bladder Cancer

Views

Total views

1,849

On Slideshare

0

From embeds

0

Number of embeds

1

Actions

Downloads

88

Shares

0

Comments

0

Likes

11

×