1.
Management of Urinary
Bladder
By
Dr Parneet Singh
Moderator-Dr Anirudh K. Punnakal

2.
Stage Wise Treatment

3.
Aim of Management of Bladder cancers- Stage wise
•Superficial bladder cancer- prevent recc and progression to muscle
invasive cancer.
•Muscle invasive bladder cancer- patient selection for cystectomy and for
bladder preservation protocol and for integrated systemic chemotherapeutic
approach.
•Metastatic bladder cancer- palliation and quality of life.
Urinary Bladder Cancer
Superficial cancer
(75%)
Musc. Invasive
cancer(20%)
Metastatic cancer (<5%)
Petrovich JCO 2001

4.
Superficial Bladder cancer

5.
Superficial Bladder Cancer
1. Non-invasive papillary tumor (Ta)
2. Tx invading lamina propria (T1)
3. High grade CIS (Tis)

6.
Risk Stratification on the basis of
prognostic factors
1. High grade or P.D tx.
2. Co-existant CIS or dysplasia in random mucosal biopsies.
3. Multiple or multicentric tumors.
4. Rapidly recc. Tumors.
5. Lamina propria invasion.
6. Ts>3cm. 7. Prostatic urethral involvement.
•Low risk- single, Ta, G1, <3cm in diameter.15% Recurrence Risk(RR)
• Intermediate Risk- Ta-1, G1-2, >3cm in dia.RR-38%
• High Risk- T1, G3, Multifocal or highly recurrent, CIS.RR-61%
Sylvester 2006 Eur Urol

7.
Treatment Options For Superficial
Bladder Cancers
1. TURBT
2. Intravesical Therapy
3. Laser
4. Photodynamic Therapy
5. Cystectomy.

8.
Trans Urethral Resection of Bladder
Tumor(TURBT)
• Under GA/Regional Anasthesia
• Remove all visible tumors
• Bimanual examination must before and after
• Ideal Method – 2 specimen to be collected
• First superficial portion of the tumour
• Deep portion along with underlying bladder muscle
The base of resection site is fulgrated

9.
TUR of Bladder Tumor (TURBT)

10.
Intravesical Therapy
• Indications:
1. Lamina propria invasion.
2. High grade Ta disease/Ta>3cm.
3. All cases of Carcinoma in situ.
4. Extravesical (Prostatic urethra inv)
5. Post resection cytology positive.
6. Multiple tx rec or rapidly rec.
All cases of superficial
bladder cancer except
low risk cases and all
cases of superficial
recurrences.
Increase Recurrence free interval by 38 %
Huncharek M JCE 2000
Perlis M 2013 Eur Urol

11.
Agents Used
1. BCG (Most common agent)
2. MMC
3. Doxorubicin/Epirubicin/Valrubicin.
4. Interferon
5. Thiotepa
6. Gemcitabine
Can be used Perioperatively or as adjuvant
therapy

12.
Administration of BCG
• Wait atleast for 10-14 days after invasive procedures.
• Avoid intake 4 hrs before instillation; empty bladder.
• Urethral catheter to drain bladder; abort procedure if traumatic.
• Recon. BCG suspension instilled slowly by gravity –don't force .
• Patient retains suspension upto 2 hrs
• Void in seated position to avoid splashing.
• For 6hrs after, disinfect voided urine with bleach.

13.
Schedule of BCG admsistration
• Usually started 2 weeks after invasive procedure
• Usually 2 inductions given without complete response
• If complete response then continued for 6 weeks
• Some suggest the benefit of maintenance therapy
• Dose reduction advised if local symptoms persist
NCCN 2015
Maintenance Therapy 3 week BCG course at Month
3rd 6th 12th 18th 24th 30th ,36th ,48th
,60th

14.
Toxicities
• Bladder irritability(dysuria,cystitis,urgency,frequency)(50-60%)
• Flu like symptoms-maliase,fever chills(45%)
• Hematuria (30-35%)
• Nausea &Anorexia(15-20%)
• Arthritis (20%)
• Headache
• BCG sepsis(1-3%)
• UTI(<5%)
• Contracted bladder(<5%) Rakesh K IJU 2008

15.
LASER
• Tumor ablation but no pathological analysis
• Hence mostly used for treating recurrences.
• Neodymium-Yittrium-Aluminium-Garnet Laser most
commonly used.
• Advantages over TUR:
1. Less bleeding
2. Less invasive (can use flexible cystoscope)
3. Less postoperative irritation.

16.
Photodynamic Therapy
• Combines non toxic photo sensitivity dyes + Visible light to destroy
cancer cells.
• Indication- CIS, Ta, T 1 tumour
• Photoforphyrin-II – 2 mg/kg body weight is given
• After 48 hrs –bladder illuminated with red light (630 mm)
• Cascade of photo chemical reaction- generate cytotoxic molecular
oxygen.
• Not routinely used

17.
Muscle invasive bladder cancer

18.
Modalities
• Surgery
• Radiation
• Chemo-radiation
• Chemotherapy

19.
Management of Muscle Invasive Bladder
Cancer
Radical Cystoprostatectomy +/-
urethrectomy- Males
Anterior Exenteration –Females
+ Bilateral Pelvic nodal dissection
Bladder Preservation
Approaches.

20.
Partial Cystectomy
• Indications
• Solitary lesion
• Bladder dome
• Less than 2 cm
• Complete excision can be done
• Possible with 2 cm margin
• Adequate bladder capacity
• No CIS
• Pt reliable for follow up
• B/L pelvic LN dissection also done till common illiac LN
NCCN 2015

21.
Radical Cystectomy
• Radical cystectomy is the gold standard for surgical management
of patients with muscle invasive bladder cancer.
• In males prostate is removed with bladder and is the equivalent of
an anterior exenteration with a pelvic lymphadectomy
• In women radical cystectomy for muscle invasive bladder cancer is
same as anterior exenteration with pelvic LN dissection.
• It includes removal of the uterus, fallopian tubes, ovaries, bladder,
urethra, and a segment of anterior vaginal wall with LN dissection

22.
Urinary diversion: Ileal Conduit
• Urine empties through
stoma
• No reservoir therefore
incontinent

23.
Urinary diversion: Ileal reservoir
• Kock’s pouch
• Reservoir created
from ascending
colon and terminal
ileus

24.
Urinary Diversion: Ureterostomy
• Ureterostomy
Divert urine directly to
skin opening
Must wear bag or pouch
after surgery

25.
Lymphadenectomy
• Pelvic lymphadenectomy done to asses the local extent of
disease.
• Usually pelvic LN-internal illiac,external, illiac,obturaor and
common illiac removed
• Extended lymph node dissection should include the distal
para-aortic and paracaval lymph nodes as well as the presacral
nodes
• Lymph nodes positive disease needs post op RT
• At least 15 nodes should be removed
Dhar 2008 J Urol
Leissner 2004 J Urol

26.
Bladder Preservation Approaches
1. Radical radiotherapy.
2. Concurrent chemoradiotherapy.( European approach)
3. Induction chemoradiotherapy f/b consolidation
chemoradiotherapy.(RTOG/MGH protocol)
4. Neoadjuvant chemotherapy f/b chemoradiotherapy.
5. Chemoradiotherapy f/b adjuvant chemotherapy.

27.
Radiotherapy
• Traditionally RT alone was given only for unfit/older pts.
• Definitive radiotherapy gives consistent and reproducible effects.
• It’s a viable option for bladder preservation.
• Results are better in younger, fitter and in those without extravesical
disease.
• Poor prognostic factors in Radical cystectomy hold true for radical
radiotherapy series also.

28.
Preoperative radiotherapy
• Tumor size reduction in locally advanced ,muscle invasive disease
• Downstaging of disease
• Decrease in incidence of local recurrence following radical cystectomy
• Decrease in incidence of distant metastasis
• Improvement of survival
• No increase in incidence of surgical complications.
• Disadvantage :
i) Possibility of problems in interpreting pathologic finding in
cystectomy & lymphadenectomy
ii) Possibility of side effects of operating on previously irradiated tissue
• Dose schedule - 40 - 50 Gy / 4 – 5 wks Rodel C JCO 2002
Efstathiou Eur Ural 2012

29.
Post operative radiotherapy
• Indications – i) Extravesical disease
ii) Positive resection margins
iii) Pelvic LN involvement
iv) Perinodal extension
• Advantage – Availability of pathologic staging
• Allows administration of adjuvant irradiation to those having
high probability of tumor recurrence
• Disadvantage- increased small intestine toxicity
• Dose schedule- 40-50 Gy/ 5-6 weeks @ 1.8-2Gy/ #
MIllikan JCO 2001

30.
Ideal candidate for definitive Radiotherapy
• Disease confined to the bladder
• With good bladder function
• cT2 tumor
• No associated CIS
• Willingness for prolonged course of therapy & regular follow
up
Cozzarini IJROBP 1999

31.
Ideal candidate for definitive Radiotherapy
• Disease confined to the bladder
• With good bladder function
• cT2 tumor
• No associated CIS
• Willingness for prolonged course of therapy & regular follow
up
Cozzarini IJROBP 1999

32.
Contraindications of pelvic Radiotherapy
• Pt with active inflammatory bowel disease
• Previous pelvic irradiation
• Pts with extensive bladder CIS are at high risk for tumor
recurrence after RT so cystectomy should be done

33.
Bladder : EMPTY or FULL
• Empty bladder –
• More reproducible
• More comfortable to patient
• Overall irradiated volume is smaller.
•
• Full bladder –
• Displaces small intestine & some part of rectum out of radiation
portals
• AT Max
• Urine voiding then treat after 15 min

34.
Conv. Radiation Portals
• ANTERIOR- POSTERIOR
FIELDS :
• Superiorly -L5-S1 interface,
• Inferiorly – Lower border of
obturator foramen
• Lateraly – 1.5- 2 cm outside
the bony pelvic wall
• Anterior field should not
include femoral heads &
neck.
• Upper corners can be
shielded to reduce small
bowel volume.

35.
In 4 field Tech. LATERAL FIELDS
• Superior and inferior
borders same
• Anterior border- 1.5-2
cm in front of anterior
bladder wall as seen on
imaging study
• Posterior border – 2.5 cm
posterior to the most
posterior aspect of the
bladder and falls within
the rectum

36.
Two phase approach
• Phase I -
• The whole pelvis
• The pelvic lymph nodes
 To include
• The whole Bladder
• Proximal urethra
• Any extravesical disease spread
• Any region deemed to be at risk of microscopic disease spread.

37.
Boost fields
• Phase II
• Either The whole bladder or
• Only the involved part of bladder with at least 2 cm
margin
• Techniques
1) 2 lateral fields
2) oblique fields

38.
Dose Fractionation Schedule
• 1.8- 2 Gy / #, to a total dose of 45 – 50 Gy to the whole pelvis
• Followed by a boost to smaller volume to a combined total
dose of 60-65 Gy

39.
• In expanding the CTV to the planning target volume (PTV),
accepted standard practice is to add isotropic margins of 1.5 to
2 cm uniformly around the bladder or bladder tumor in three
dimensions.
• Allow for organ motion and for errors in target delineation and
daily treatment set-up.
• ICRU 62 advocates subdivision of treatment margins into
• Internal margins (IM), to account for variations in the size,
shape, and position of the organ,
• Set-up margins (SM), to account for uncertainties in patient
positioning and beam arrangement

40.
Field at cranial End

41.
Mid Field

42.
Field at caudal End

43.
Palliative radiotherapy
• Rapid resolution of symptoms
• Severe gross hematuria
• Pelvic pain
• Ureteral obstruction.
• Dose schedule – 10 Gy / single fraction to pelvis.

44.
Patient Care During RT
• High fluid intake
• Skin care
• Diarrhea – oral medications, suspension of treatment
• Cystitis / urinary frequency- urine for bacteriological
examination

45.
Side effects
• ACUTE TOXICITY :
• Cystitis – frequency, urge incontinence, dysuria.(55-60%)
• Diarrhea(30-40%)
• Mild proctitis(25%)
• LATE SEQUELAE:
• Teleangiectasia of bladder mucosa
• Hematuria
• Rectal bleeding
• Contraction of bladder
• Reduced bladder capacity
NCCN 2015

46.
Comparsion cystectomy & bladder
presevation protocols.
Survival is equivalent

47.
Chemotherapy

48.
Chemotherapy
• NEOADJUVANT
• Down staging
• Inoperable
• Rx of micrometastasis
• CONCURRENT CHEMO
• ADJUVANT
• Some studies showed increased survival.

49.
Chemotherapy
FOUR – DRUG COMBINATION M-VAC
• Methotrexate 30 mg/m2 – 1,15 & 22
• Vinblastine 3 mg/m2- 2,15 & 22 Q28 days for 6 cycles
• Adriamycin 30 mg/m2 on day 2
• Cisplatin 70 mg/m2 on day 2
•
• Gemcitabine +cisplatin
• Gem-1000mg/m2-D1,8,15 Q28 days for 6 cycles
• Cisplatin-D1or2
• For concurrent inj Cisplatin 40mg/m2

50.
Chemotherapy for bladder cancer
Combination chemotherapy.
RR
MVAC 10-25%
Gem/ Cisplatin 40-50%
Gem/ Carboplatin 65%
Taxol / Carboplatin 40-60%
Von Dar Massse 2000
JCO

51.
Adjuvant Chemotherapy
• Local definitive treatment is not delayed.
• Better patient selection on surgical and pathological findings
• 5 RCT addressed this issue of adjuvant chemotherapy after local
therapy either after Sx or RT/RTCT
Author N Standard arm Adjuvant
arm
results
Skinner et al 91 cystectomy C+CAP Benefit
Stockle et al 49 cystectomy C+MVAC Benefit
Struder et al 77 cystectomy C+CDDP No benefit
Freiha et al 55 cystectomy C+CMV Benefit
Bono et al 83 cystectomy C+CM No benefit

52.
Follow up
NCCN 2015

53.
Thank You

54.
Prognostic Factors
• Tumor stage
• Tumor morphology
• Absence of concomitant Tis
• Presence of intravesical Vs extravesical tumor
• Completeness of TURB
• Solitary Vs multiple bladder tumors
• Presence of ureteric obstruction
• Presence of complete response after EBRT
• Radiation dose