This document discusses bladder cancer including incidence, risk factors, histology, staging, and treatment approaches. Some key points:
- Bladder cancer is the 4th most common cancer in Egypt and the 6th-7th most common in the USA. Risk factors include occupational exposures, Schistosomiasis, smoking, and certain drugs.
- Treatment depends on stage and grade. Non-muscle invasive cancers are treated with transurethral resection and intravesical therapies. Muscle invasive cancers require radical cystectomy, chemotherapy, or chemoradiation.
- Egyptian bladder cancers have higher rates of squamous cell carcinoma compared to the USA due to higher Schistosomiasis rates
urinary bladder malignancy
incidence
risk factors and pathogenesis
staging of the disease
histopathology
transitional and non transitional cell carcinomas
clinical features
laboratory findings
imaging
molecular markers
treatment options
chemotherapy
radiotherapy
surgery
Target audience : Oncology fellows and Oncologists.
Four challenging cases of Bladder cancer and managing decisions including latest management principles are discussed here.
Bladder Cancer Diagnostic-Initial Team ProjectSagar Desai
A mini-project to find biomarkers for bladder cancer diagnosis. We narrowed down our list of viable candidates down to three that could be used in combination to provide sensitivity and specificity values greater than 94%. Furthermore, we calculated long-term monitoring and payor costs as well as potential profit.
intravesical Gemcitabine in High risk non muscle invasive bladder cancerDr Mayank Mohan Agarwal
Gemcitabine, in conjunction with cisplatin, is well established chemotherapeutic agent for systemic treatment of advanced bladder cancer (urothelial carcinoma). however, its role in high risk NMIBC is controversial.
This presentation describes the chemical properties of gemcitabine (which make it the ideal molecule for intravesical therapy), discusses the role in primary NMIBC, recurrent NMIBC (high risk) and compares its safety and efficacy with intravesical BCG.
This is a powerpoint on Bladder Cancer. Sources are on the last slide of the powepoint! No copy right intended! Enjoy! I hope you learn a lot and I hope you live your life Bladder Cancer free! Also the red words are what I would say during the presentation, basically extra details! So keep that in mind!
-Shelby
urinary bladder malignancy
incidence
risk factors and pathogenesis
staging of the disease
histopathology
transitional and non transitional cell carcinomas
clinical features
laboratory findings
imaging
molecular markers
treatment options
chemotherapy
radiotherapy
surgery
Target audience : Oncology fellows and Oncologists.
Four challenging cases of Bladder cancer and managing decisions including latest management principles are discussed here.
Bladder Cancer Diagnostic-Initial Team ProjectSagar Desai
A mini-project to find biomarkers for bladder cancer diagnosis. We narrowed down our list of viable candidates down to three that could be used in combination to provide sensitivity and specificity values greater than 94%. Furthermore, we calculated long-term monitoring and payor costs as well as potential profit.
intravesical Gemcitabine in High risk non muscle invasive bladder cancerDr Mayank Mohan Agarwal
Gemcitabine, in conjunction with cisplatin, is well established chemotherapeutic agent for systemic treatment of advanced bladder cancer (urothelial carcinoma). however, its role in high risk NMIBC is controversial.
This presentation describes the chemical properties of gemcitabine (which make it the ideal molecule for intravesical therapy), discusses the role in primary NMIBC, recurrent NMIBC (high risk) and compares its safety and efficacy with intravesical BCG.
This is a powerpoint on Bladder Cancer. Sources are on the last slide of the powepoint! No copy right intended! Enjoy! I hope you learn a lot and I hope you live your life Bladder Cancer free! Also the red words are what I would say during the presentation, basically extra details! So keep that in mind!
-Shelby
This is an overview of the adjuvant Tx of pancreatic CA. A Lecture that was given in the annual conference of NCI Egypt: 45 years against cancer in Egypt. Cairo, April, 2013
Principios generales del tratamiento de cáncer del pulmón de células no pequeñas. Incorporando los avances recientes con inmunoterapia, y en terapia dirigida.
This presentation covers the guidelines for follow up of patients with Hodgkin's lymphoma after they achieve complete remission and complete their therapy.
8. HISTOLOGY
US EGY
¢ TCC: 90% ¢ TCC: 63%
¢ SCC: 6-8% ¢ SCC: 27%
¢ Adeno: 2% ¢ Adeno: 3%
¢ Small cell: 1% ¢ Undifferentiated: 2%
systemic chemotherapy regimens used to treat TCC
are ineffective in pure SCC or Adeno
If mixed tumor only TCC responds
10. TNM STAGING 2010
URINARY BLADDER
¢ T0: non-invasive
— Ta: Noninvasive papillary carcinoma
— Tis: Carcinoma in situ “flat tumor”
¢ T1: mucosa or submucosa
¢ T2: muscle
— T2a: inner half
— T2b: outer half
¢ T3: outside muscle (adventitia)
— T3a: microscopic (histology, no
masses
— T3b: macroscopic (mass)
¢ T4: surroiundings
— T4a: prostate, uterus, vagina
— T4b: pelvic or abdominal
T T T T4 T4 M1
¢ N1: regional LN+
1 2 3 a b — N1: Pelvic LNs (1)
— N2 : pelvic LNS (>1)
N0 I II III III IV IV — N3: common iliac LN
N1- IV IV IV IV IV IV
M1: Distant mets
SIMPLIFICATION
3
¢
-I: T1 -II: T2
-III: T3/T4 a -IV: T4b OR LN+
OR M1
11. STAGING
T0: non-invasive
Ta: Noninvasive papillary carcinoma
Tis: Carcinoma in situ “flat tumor”
T1: sub-epithelial connective tissue
T2: Tumor invades muscle
T2a: inner half
T2b: outer half
T3: Tumor invades perivesical tissue
T3a: Microscopically
T3b: Macroscopically (extravesical mass)
T4: surroundings
T4a: prostate, uterus, vagina
T4b: pelvic wall, abdominal wall
N1: 1 pelvic LN
N2: > 1 pelvic LN
Tis/0 T1 T2 T3 T4 M1=IV
N3: common iliac LN
N0 0 I II III T4a: T4b: IV
M1: distant mets III IV
N1-3 IV
12. MANAGEMENT OF BLADDER CA
¢ Cystoscopy and biopsy:
— See lesions
— Biopsy and muscle should be included
— We will reach to a conclusion:
— MUSCLE IS INVADED OR NOT
¢ Not invaded àTURB
¢ Upper UT imaging
¢ CT if sessile or high grade T is suspected
¢ Invaded à CT:
¢ LN small (negative): T2,T3, T4a: cyatectomy
¢ LN large: biopsy: negative
— Positive:
13. NON MUSCLE INVASIVE
Grade Cyctectomy TURB IVsT+ Cystectomy
Tis High No Yes BCG Resistent
/relapsed
Ta Low No Yes May (chemo, mito) //
Once
? After 6ms
Ta high No Yes BCG > Chemo //
T1 Low No Yes BCG* If residual
Mito** //
T1 high May Yes BCG* if residual
Mito** //
+ not if extensive TURB or perforation
* Whether residual or no residual
** chemotherapy only if no residaul
14. INTRAVESICAL CHMOTHERAPY
¢ Drugs
— Chemotherapy
¢ Alkylating agents: thiotepa, mitomycin C (40mg in 20 cc st
Water),
¢ Anthracyclines: doxorubicin (50 mg in 25 cc St water),
epirubicin, valrubicin
¢ Value:
— Acts by diffusion
— Prevent seeding and Reduce recurrence by 6%
— No reduction in disease progression or mortality
— Within 6 Hrs post TUR, Not if extensive TURB or
perforation
— Overnight fast, empty bladder before
— Keep for .5 hr (post TUR) or 2Hrs, supine and prone (air
bubble)
— Alkalanize urine with mitomycin
15. INTRAVESICLA IMMUNOTHERAPY
— Immunotherapy
¢ BCG (81 mg for TheraCys and 50 mg for TICE, both in 50 cc
physiologic saline)
— Value:
¢ Acts by enhancing immune response, drawing lymphocytes
and macrophages to the bladder and stimulating a cellular
(TH1) immune response
¢ Not immediate (at least 1-2 wks post TUR)
¢ Weekly x 6 w
¢ Maintenance
¢ (3 app x q 3ms)
¢ 3 weekly at 2, 6, 12, 18, 24, 30, 36 ms XXXX?
¢ NOT WITH CIPRO
16. MUSCLE INVASIVE
N Cystectomy Chemotherapy Radiotherapy
N- T2* Radical Neoadj or adjuvant No
Partial Neoadj or adjuvant May be used instead of CT
No CRT CRT
N- T3* Radical Neoadj or adjuvant No
No CRT CRT
N- T4a If possible CRT or chemo CRT or chemo
1st or after (Neoadj or adj) (Neoadj or adj)
Neoadj
N- T4b If possible CRT or chemo CRT or chemo
after Neoadj (Neoadj or adj) (Neoadj or adj)
N+ If possible CRT or chemo CRT or chemo
after Neoadj (Neoadj or adj) (Neoadj or adj)
M1 No Yes may
17. PROGNOSTIC FACTORS
¢ Stage :
— depth of invasion
¢ Grade:
— Low grade: 1-2
— High grade: 3-4
19. TREATMENT MODALITIES
¢ Resection:
— TURBT: ONLY FOR non-muscle invasive
— Cystectomy:
¢ Partial cystectomy : selected cases of muscle invasion
¢ Radical cystectomy: standard treatment of muscle invasive
tumors and as salvage therapy
¢ Drug therapy:
— Local (intravesical): ONLY FOR non-muscle invasive
¢ Immunotherapy: BCG or INF
¢ Chemotherapy: MMC, Doxorubicin or Valrubicin, thiotepa
— Systemic (IV) chemotherapy: ONLY for muscle
invasive
¢ Radiotherapy: ONLY for muscle invasive
20. TREATMENT: NON-MUSCLE INVASIVE
¢ Includes: Ta, Tis, T1
¢ Tx:
— Repeated TURB
— Post TURB intravesical therapy:
¢ depends on grade and depth of invasion that determines:
¢ Bladder recurrence risk
¢ Progression to muscle invasion risk
¢ Modes:
¢ Adjuvant: to prevent bladder recurrence: MAINLY
¢ Complementary: to eradicate residual disease: RARELY
— Cystectomy: rare
21. TREATMENT: NON-MUSCLE INVASIVE
¢ Tis (CIS), always high grade
¢ Tx:
— TURB
— Post TURB intravesical BCG
therapy Weekly x 6
— Follow up: cystectoscopy +
cytology + imaging of upper
Urinary tract q3 m x 24m,
then increase intervals
— Recurrence:
¢ TURB +
¢ Adjuvant intravesical therapy
according to grade and
depth of invasion
¢ Follow up: cystectoscopy q3
m
22. TREATMENT: NON-MUSCLE INVASIVE
¢ Ta (papilloma), low grade ¢ Ta (papilloma), high grade
¢ Tx: ¢ Tx:
— TURB — TURB
— Post TURB intravesical therapy: — Post TURB intravesical therapy:
¢ None ¢ None
¢ Adjuvant intravesical ¢ Adjuvant intravesical BCG:
chemotherapy (Mitomycin C): ¢ Adjuvant intravesical
¢ Single chemotherapy (Mitomycin C):
¢ Within 24 Hours form TURB ¢ Single
— Follow up: cystectoscopy + ¢ Within 24 Hours form TURB
cytology q3 m x 12 m, then — Follow up: cystectoscopy +
increase intervals cytology + imaging of upper
Urinary tract q3 m x 24m, then
— Recurrence: increase intervals
¢ TURB + — Recurrence:
¢ Adjuvant intravesical therapy ¢ TURB +
according to grade and depth of ¢ Adjuvant intravesical therapy
invasion according to grade and depth of
¢ Follow up: cystectoscopy q3 m invasion
¢ Follow up: cystectoscopy q3 m
23. TREATMENT: NON-MUSCLE INVASIVE
¢ Persistent or recurrent Ta and Tis
— TURB+/- IVTà recurrence/persistence at W12à TURB+IVT à still recurrence or
persistence at W 24
¢ Tx:
— Cystectomy is the first option
— TURB and Post TURB intravesical therapy may be considered to avoid cyctectomy
¢ Use different agents
¢ Chemo: MMC, Valrubicin
¢ BCG + INF a
¢ Follow up: cystectoscopy + cytology + imaging of upper Urinary tract q3 m x 24m, then q 6m x 24
m
¢ Recurrence/persistence: cystectomy
¢ Another scenario:
— TURB+/- IVTà recurrence/persistence at W12à TURB+IVT à CR:
— Maintenance BCG
— Follow up: cystectoscopy + cytology + imaging of upper Urinary tract q3 m x
24m, then q 6m x 24 m
¢ Recurrence/persistence: TRUB + different IVT or cystectomy
24. TREATMENT: NON-MUSCLE INVASIVE
¢ T1 , low risk ¢ T1, high risk
— No high risk features — multifocal lesions,
— vascular invasion,
— recurrence after BCG
¢ Tx:
— High grade.
— TURB
— Post TURB intravesical therapy: ¢ Tx:
¢ Adjuvant intravesical BCG: — TURB
¢ Adjuvant intravesical chemotherapy — Post TURB intravesical therapy:
(Mitomycin C): ¢ Adjuvant intravesical BCG:
¢ Single ¢ Adjuvant intravesical chemotherapy
¢ Within 24 Hours form TURB (Mitomycin C):
— Follow up: cystectoscopy + cytology ¢ Single
q3 m x 12 m, then increase intervals ¢ Within 24 Hours form TURB
— Cystectomy
— Recurrence: — Follow up: cystectoscopy + cytology
¢ TURB + + imaging of upper Urinary tract q3
¢ Adjuvant intravesical therapy m x 24m, then increase intervals
according to grade and depth of — Persistence after conservative
invasion management :
¢ Follow up: cystectoscopy q3 m ¢ Cystectomy
25. FOLLOW UP
¢ Low risk lesion: high risk lesions+
Cystoscopy and cytology Cystoscopy and cytology
¢ imaging upper tract
¢ q3 m x 12 q3 m x24
¢ Then increasing q 6m x 24
26. TREATMENT: MUSCLE INVASIVE DISEASE
¢ Workup:
— Lab: CBC, chemistry, Alk phos
— Cystoscopy, EAU/TRUBT
— Imaging:
¢ Chest Xray
¢ CT/MRI of abdomen and pelvis
¢ +/- Bone scan
¢ Aim:
Tis/0 T1 T2 T3 T4 M1=IV
— Organ confined T2, N0, M0 N0 0 I II III T4a: T4b: IV
III IV
— Non-organ confined T3, T4, N1, M0
N1-3 IV
— Metastatic disease M1
27. ORGAN CONFINED (T2) DISEASE
¢ Surgery (cyctectomy):
— Primary Tx
— radical : standard particularly in recurrence
— Partial (segmental)
¢ More in dome and solitary
¢ Less in neck, trigone and multiple or associated Tis
¢ Chemotherapy:
— Cisplatin-based
¢ Neoadjuvant: in T3 or T2 or
¢ Adjuvant : pT3 and pT4 and LN+
¢ RT:
¢ Adjuvant: pT3 and pT4, LN+, SM+ or high grade
¢ Concurrent chemoradiotherapy (CCRT):
— Preoperative: in advanced disease
— Definitive: in severe comorbidities and poor PS
— If CCRT is not tolerable: chemo or radio can be given alone
32. CYSTECTOMY
¢ Radical cystectomy: standard
— Male:
¢ removes bladder, prostate, seminal vesicles
— Females:
¢ Removes bladder and maybe uterus, ovaries and tubes
— Pelvic LND:
¢ decreases recurrence and
¢ increase OS
— Urinary diversion or neobladder
¢ Partial systectomy: selective
— More in dome and solitary
— Less in neck, trigone and multiple or associated Tis
— Recurrence after partial cystectomy:
¢ Consider as new cancer
¢ Non-M invasive: TURB and IVT
¢ M invasive: as usual but do not consider conservation
again
33. NEOADJUVANT CHEMO
¢ Cisplatin-based
— MVAC
— CMV
— Cis-Gem
— Cis-adia
— Cis-Mtx
¢ 3 cycles
¢ In T3 (category 1) or T2 (category 2A)
34. NEOADJUVANT M-VAC CHEMO
¢ Grossman et al, N Engl J Med. 2003;349(9):859-66.
¢ MVAC x 3 q 28d
— Mtx: 30 mg sm d1, 15, 22
— Vinblastine: 3 mg sm d2, 15, 22
— Adrai: 30 mg sm d2
— Cisplatin: 70 mg sm d2
¢ T2-T4a
¢ Pathological CR: 38%
37. Figure 1. Survival
among Patients
Randomly Assigned
to Receive
Methotrexate,
Vinblastine,
Doxorubicin, and
Cisplatin (M-VAC)
Followed by
Cystectomy or
Cystectomy Alone,
According to an
Intention-to-Treat
Analysis.
40. NEOADJ CIS-ADRIA OR CIS-MTX
¢ Sherif et al, Eur Urol 2004;45:297–303.
¢ Combined analysis of 2 trials
¢ Regimens:
— Cis 70 mg/sm & A 30 mg/sm q 3w x2 + RT
— Cis 100mg/m & Mtx 250mg/sm q3w x 3 NO RT
¢ OS HR 0.80 (95% CI 0.64–0.99) in favor of neoadjuvant
treatment.
¢ 5 Y OS was 56% for neoadjuvant and 48% in the control
group,
¢ 8% reduction in risk of death.
43. NEOADJUVANT CHEMOTHERAPY FOR TRANSITIONAL CELL
CARCINOMA OF THE BLADDER:
A SYSTEMATIC REVIEW AND META-ANALYSIS.
¢ Winquist et al, J Urol. 2004 Feb;171(2 Pt 1):561-9.
¢ 11 trials (2,605 patients)
¢ Conducted between 1984 and 2002
¢ TCC stages II and III (T2-T4, Nx-N3, M0)
¢ Pooled HR of death was 0.90 (95% CI 0.82 to 0.99, p =
0.02).
¢ Absolute OS benefit of 6.5% (95% CI 2 to 11%) from
50% to 56.5%
¢ PFS benefit consistent with OS benefit
¢ CR rates: 14-38%, Major Pathological response: 43%
¢ Major pathological response was associated with
improved OS in 4 trials
46. CONCURRENT CHEMORADIOTHERAPY
¢ Improved local control of invasive bladder
cancer by concurrent cisplatin and
preoperative or definitive radiation. The
National Cancer Institute of Canada Clinical
Trials Group.
¢ Coppin et al, J Clin Oncol. 1996 Nov;14(11):2901-7.
¢ RCT in 99 patients
¢ T2 to T4b TCC
¢ Randomized to CCRT or RT
— (cisplatin 100 mg/m2 at 2-week intervals x 3 cycles
concurrent with pelvic radiation), or RT (radiation without
chemotherapy)
48. CCRT VS RT IN TCC OF BLADDER
¢ Pelvis relapse significantly lower in CCRT
¢ Distant relapse were similar
¢ PFS better with CCRT (P 0.08)
¢ 3 y OS rates 47% in CCRT and 33% in RT (P0.34)
50. ADJUVANT CHEMOTHERAPY
¢ Non-urothelial CA
— No data in any stage
¢ Urothelial CA
— Conflicting data
— Many trials showing benefit are not randomized
— Metaanalysis of 6 trails
¢ 25% mortality reduction
¢ But many limitations
¢ Regimens
¢ GC
¢ MVAC, MVEC
¢ CAP
¢ No. of cycles: at least 3
54. ADJ RT
¢ Dat are scarce
¢ Possible role in T3a, T3b, T4a
— Due to High recurrence (30% that increase to 60% if
SM+)
¢ May be given with concurrent cisplatin
¢ Adj chemotherapy is also indicated in these cases
¢ Adj RT and Adj CT are not give together
55. BLADDER PRESERVATION
¢ Partial cystectomy alone
¢ Chemotherapy then partial cystectomy
¢ TUR alone
¢ TUR followed by
— Chemotherapy and radiotherapy (BEST)
¢ Cisplatin w1, 4 +/-8
— Chemo only
— Radio only
¢ Indications
— Urothelial ca
— Unfit pts
— Refusing pts