2. CASE
• 74y/M
• Presented with painless intermittent heamturia
• Chronic smoker
• Not known case of HTN/DM/TB/BA
• P.S-ECOG 2
• Registered in RT on 1/1/15 RT no. 24864/15
3. INVESTIGATIONS
• CECT abd/pelvis #63166/14 - Two lobulated heterogeneously enhancing intraluminal
lesion in anterosuperior wall -2.9X2.2X2.5 and 1.2X1.X1.1 cm
• TURBT- S-26721/2014- Tumor 1- High grade papillary urothelial carcinoma, NMIBC
Tumor 2 High grade papillary urothelial carcinoma, muscle invasive
• Bone scan- #68477/14; 11/12/14- No e/o mets
4. TREATMENT GIVEN
• Started on chemotherapy gemcitabine (1.2g/m2) + cisplatin(70mg/m2)
D1,D15- 4 cycles last on 22/4/15
• CECT chest/abdomen #20212/15 on 21/4/15- residual asymmetric mural
thickening – good response
• Patient given option of radical cystectomy and bladder preservation- opted
bladder preservation
7. • Post RT- #29369/15; 30/7/15- Mild asymmetric mural thickening ~1cm
involving anterior wall of urinary bladder close to dome, mild perivesical fat
stranding
• Patient planned for adjuvant chemotherapy but patient refused
• Kept on follow up
8. FOLLOW UP
• CECT chest/abdomen #39705/15 on 4/11/15 - 4.6 mm minimal asymmetry at
dome of bladder, no perivesical fat stranding
• CECT chest/abdomen #3576/15/16 on 19/2/16 - 16 mm asymmetric thickening
• CECT chest/abdomen #13282/16 on 15/6/16- mild ~7 mm asymmetric thickening
• CECT chest/abdomen #18859/16 on 14/9/16- no significant asymmetric
thickening
9. PRESENT STATUS
• No complaints, no urinary complaints
• G.C good/ECOG 1
• Cect chest/abdomen #9371/17 on25/4/17 - no e/o mural thickening in
urinary bladder, minimal perivesical stranding
• Cystoscopy done on 6/10/17- no mucosal growth
10. CASE SUMMARY
74y/M
T1N0M0
T3N0M0
NACT
Gem-Cis 4
cycles last on
22/4/15
CECT s/o
90%
resolution
Radical RT
EBRT 62
Gy/31# last
on 30/6/15
2.5 YEARS
FU
Both clinical
&
Radiological
NED
Status on
Last FU
6th Oct 17
NED with
intact &
functional
Bladder
12. INTRODUCTION
• M:F- 3:1*
• 4th MC cancer among men (7%)*
• 6th to 8th decade*
Cause
Chemical
exposure
Gene
abnormalties
Chronic
irritation
*Cancer Statistics, 2016
13. • 8th mc cause of death among men *
• Responsible for about 4% of all cancer deaths among men *
• Pathologic predictors for recurrence and survival are tumor stage and nodal status
• 20-30% are MIBC *
* Cancer Statistics, 2016
14. MIBC
• 5 Yr-Survival rates after radical cystectomy*
• Death after appropriate local therapy is typically the result of systemic
disease
• Non–local regional relapses are reflective of the presence of
micrometastatic disease at the time of diagnosis
* Stein et al, 2001
Madersbacher et al, 2003
Hautmann et al, 2006
Shariat et al, 2006
Ghoneim et al, 2008
Manoharan et al, 2009
pT2 70-81%
pT3 40-52%
pT4a,b 16-44%
N+ 21-35%
N- 62-72%
16. STANDARD TREATMENT
• Radical cystoprostatectomy with b/l pelvic lymphadenectomy
• Adequate pLND dissection- not defined
• Extended LND if CECT or frozen section shows paraortic spread
• Urinary diversion- incontinent or continent
17. PATTERN OF FAILURE AFTER CYSTECTOMY
Explanation
• Tumor cell spill in the pelvis during surgery
• Presence of tumor cells beyond the margins of surgical excision
• Dissemination of tumor cells to distant sites during surgical manipulation
RC
LOCAL
RECURRENCE
URETERAL
RECURRENCE
DISTANT
METS
5–31%
18. • 10 randomised trials, 2688 patients
• All platinum-based
• overall survival increased from 45% to 50%
• Update in 2005, confirmed the same
• Other trials showed similar results*
2003
*BA06 30894 trial
Nordic studies
a 5% absolute
improvement in
survival at 5
years
19. Neoadjuvant chemotherapy
• Delayed surgery
• Interferred with pathological aspect
Adjuvant chemotherapy
• Is administered after accurate pathological staging,
• Treatment in patients at low risk for micrometastases is avoided
• No delay in definitive surgical treatment
20. • Included 6 trials
• All had platinum based chemotherapy
• Absolute improvement OS of 9% and DFS of 12% in 3 years
• Update in 2013 showed HR 0f 0.66
• This disease-free survival benefit was more apparent among
those with positive nodal involvement
21. PRE-OPERATIVE AND POST OPERATIVE RADIOTHERAPY
• Metanalyses * six randomized trials indicated no benefit to preoperative
irradiation collectively
• Adjuvant radiotherapy for bladder cancer has succeeded in decreasing the
local recurrence to a great extent in prospective randomized trials *
• Fear of GI complications resulted in infrequent use of PORT *
• Modern radiotherapy has the capability of increasing the effective dose to the
tumor target and decreasing the dose to the surrounding organs at risk
• Need to revisit PORT
*Zaghloul MS et al 1992
*Huncharek et al 1998
*Reisinger S et al 1992
22. LIMITATIONS OF RADICAL CYSTECTOMY
• Significant risk of perioperative morbidity and mortality much improved now - 5.1-
8.1% 90 day mortality
• High morbidity – 90 day complication 28-64%
Acute gastrointestinal (29%), infection (25%), and wound-related complications (15%)
• High readmission rate
• Erectile dysfunction
• Urinary leakage/ incontinence
• Altered body image orthotopic diversion
• Medical contraindications
• Poor performance status – most bladder cancer patients are old
L. S. Hounsome et al 2015
A. S. Zakaria et al 2009
J. P. Stein et al 2001
R. E. Hautmann et al 2010
24. EVOLUTION OF DEFINITIVE ROLE OF RADIOTHERAPY
Prompted more generalized application in muscle-invasive bladder cancer
Apparent success in some instances and the efficacy of salvage cystectomy in others
First provided to patients who were not considered suitable surgical candidates
26. • No randomised prospective trial to compare radical cystectomy vs definitive
radiotherapy
• UK SPARE (Selective Bladder Preservation against Radical Excision) trial – phase I/II
trial
MIBC neoadjuvant chemotherapy
trial closed due to poor accrual
RC CHEMORT
27. • 20,822 cases of bladder carcinoma
diagnosed in Ontario between 1982 and
1994
28. • Multicenter, phase 3 trial
• Randomly assigned 360 patients with MIBC to undergo
RT with or without synchronous chemotherapy
• 5 yr OS 48% in chemoRT and 36% in RT alone
• grade ¾ toxicity 8.3% vs. 15.7%, P=0.07
32. PATTERN OF FAILURE AFTER CHEMORT
• A significant proportion of patients will experience local failure- trial BC2001
• Most recurrences will occur within the first two to three years after cystectomy
TURBT
INTRAVESICAL
CHEMO
SALVAGE CYSTECTOMY SYSTEMIC THERAPIES
PATIENT SELECTION
35. 46%
45%
48%
41%
5 YR OS 10 YR OS
OVERALL SURVIVAL
Intact Bladder Cystectomy
ARM 5 Yr OS 10 Yr OS
Intact Bladder 46% 45%
T2 57% 50%
T3-T4a 35% 34%
Cystectomy 48% 41%
T2 57% 39%
T3-T4a 42% 42%
overall 54% 36%
T2 62% 41%
T3-T4a 47% 31%No patient required cystectomy for a radiation complication
36. • 468 patients five phase II studies and one phase III study
• Evaluated bladder preserving combined-modality therapy (CMT) for muscle-
invasive bladder cancer (MIBC), reserving cystectomy for salvage treatment
• The 5- and 10-year OS rates were 57% and 36%, respectively, and the 5- and
10-year DSS rates were 71% and 65%, respectively
37. 221 patients, T2-4Nx-0M0 bladder cancer, Treated on protocols 1986-2000, median follow up : 6.3 years
Urodynamic study, QOL questionnaire
• 78% had compliant bladders with normal capacity and flow parameters
• 85% had no urgency or occasional urgency
• 25% had occasional to moderate bowel control symptoms
• 50% of men had normal erectile function
38. • 93 patients were given self made questionnaire to analyse urinary, sexual, social functions
• QOL after cystectomy, marked by stoma presence, was reduced by a lack of sexual activity
and a worsened physical condition, but social and recreational life were little affected
39. 157 patients with Bladder Preservation who survived 2 to 13 years (Median follow-up - 5.2 years)
22% - Grade 1
10% - Grade 2
7% - Grade 3 (5.7% GU, 1.9% GI)
0% - Grade 4
0% - Grade 5
Similar results
Trans Tasman Radiation Oncology Group. Radiother Oncol 81:9-
17, 2006
The European perspective. Semin Radiat Oncol 15:28-35, 2005
Grade $ 3 late RTOG Dmax <65 <6
40. IMPACT OF NEOADJUVANT CHEMOTHERAPY ON ORGAN PRESERVATION IN
MUSCLE INVASIVE URINARY BLADDER CARCINOMA
Chinna Babu, Narendra Kumar, Santosh Kumar
• 20 patients of MIBC
• After Neoadjuvant chemotherapy
Partial Response(PR) >50% -18(90%) patients, received radical radiation
PR <50%- 2 patients(10%) underwent radical cystectomy
• Post RT- Complete response in all 18 patients
• With median follow up of 14 months--
2 patients (10%) had bladder recurrence-underwent salvage cystectomy
1 patient developed distant failure
41. Those involved in the management of muscle invasive bladder cancer should “take a
leaf from the book” on sarcoma and breast cancer management, where
multidisciplinary collaborative approach with knowledge and respect for the benefits
and shortcomings of individual treatment modalities has led to a standard of organ
preservation.
42. CONCLUSION
Traditional thinking
In most instances tumor will persist or recur after definitive RT will
require salvage cystectomy
Radiation may compromise the suitability for appropriate surgery
But multiple studies have shown
Bladder preservation almost as good as radical cystectomy
Provides good bladder functioning
Not every case requires salvage cystectomy
Radiation does not hinder salvage cystectomy
For success of bladder preservation treatment
Better selection of patients and
Patient motivation for follow- up is must
No clots, blood in urine, increase in frequency, burning
4th mc after prostate, lung and colorectal
Genetic- alteration in chr 9, EGF, ki67, cyclin D1, MMP, TIMP, Rb/p53 gene
Chemical- aromatic amines, aniline dyes, nitrites, nitrates
Genetic polymorphism increases susceptibility
Smokers- 3 fold increase ex smokers-2 fold increase
Chronic irriatation –schistostoma hematobium, prolonged catheters, recurrent UTIs, indwelling catheters
Pelvic radiation-1.7
prostate cancer can be present in
upward of 23% to 54% of radical cystoprostatectomy
Should be done within 12 weeks of TUR (Sanchez-Ortiz and colleagues (2003))
In men- includes excision of the surrounding perivesical soft tissue, prostate, and seminal vesicles
In women- includes the ovaries, uterus with cervix, and anterior vagina
includes all lymphatic tissue around the common iliac, intercommon iliac, internal iliac, and obturator bilaterally
Ileal conduit or abdominal or orthotopic ileal neobladder or MAINZ pouch is made
Modern radiotherapy has the capability of increasing the effective dose to the tumor target and decreasing the dose to the surrounding organs at risk, thereby raising the therapeutic ratio both in the pre- and post-operative settings
Recurrence of disease often occurs within the first 2 years following
surgery, with median recurrence times of 7 to 18 months reported
in large series
In modern days, postoperative mortality following
RC is limited to the level of 1–4%.
orthotopic diversion
Remives cutaneous stoma, intermittent catherization
chemoRT- for bladder preservation should
have good baseline bladder function, have a complete resection of
all visible tumors endoscopically, have small solitary tumors with
limited CIS, and have no evidence of hydronephrosis
At 2 years, rates of locoregional disease–free survival
67% in the chemoradiotherapy group and 54% in the radiotherapy group
