This document discusses bladder preservation as an alternative to radical cystectomy for muscle-invasive bladder cancer (MIBC). It outlines the trimodality approach of maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiation. Studies have shown 5-year bladder intact survival rates ranging from 36-66% with this approach. Complete response to induction chemoradiation may allow bladder preservation. Radical cystectomy is associated with significant morbidity while bladder preservation maintains quality of life. Long-term outcomes depend on patient selection and a multidisciplinary approach can maximize organ preservation while achieving high cure rates.

1. Bladder preservation in MIBC
THE SUCCESS STORY OF ORGAN PRESERVATION!

2. BLADDER PRESERVATION - Range
• TURBT alone
• TURBT f/b RT alone
• TURBT f/b chemotherapy
Trimodality treatment
Selective bladder preservation in form of partial cystectomy

3. Trimodality treatment
1. Maximal TURBT
2. Concurrent chemo- radiation
3. Intervel early cystoscopy at end of 40- 45 Gy or 2 – 3 month after
complete RT-CT
a. i.c.o CR- complete CTRT or close surveillance
b. i.c.o PR- immediate cystectomy
4. Close surveillance with cystoscopies there after!

4. Candidates
• T2 to T4a
• Unifocal lesion less than 5 cms
• Absence of extensive CIS
• No trigone involvement or hydroureteronephrosis
• Good bladder capacity prior to treatment
• Complete TURBT
• No contraindication to chemotherapy

5. Basics of choosing a therapeutic option
1. Cure rate and survival
2. Organ preservation
3. Quality of life

6. • Ultimate aim of cancer therapy---
CURE & SURVIVAL

8. NOT TO FORGET…
• All surgical series have pathological staging versus all Bladder
preservation studies are clinical staged.
• Many cystectomy studies are retrospective analysis and hence are not
analysed with ‘intention to treat’ approach.
• Radical cystectomy series include Tis Ta T1 in their study group and
hence the results and exclude inoperable tumors( bad risk group
patients).

9.  Only comparable study will be a randomized control trial that
have clinical staging for both groups and all are analysed with an
intention to treat.
WHICH DOES NOT EXIST!!!

10. • N = 348
• Clinical stages T2-T4a
• Treated on protocols 1986-2006
• Median age 66.3 years (range 27.3–88.6)
• Median FU for those alive 7.7 years
• Actuarial endpoints included: OS, DSS

12. `
• Highlighted the implication of a complete TURBT which is an
important part of Bladder preservation treatment.

13. Shipley et al- RTOG
Tester- RTOG 8512
Coppin- NCIC

14. Kaufman(1)- RTOG 9506 Hagan – RTOG 9706
Gogna - TTROG Kaufman RTOG9906

15. • Combined analysis, RTOG 9906 & 0233*
• 2014 Abstract: ASCO Genitourinary Cancers Symposium –
• "Long-term outcomes among patients who achieve complete or near-
complete responses after the induction phase of bladder-preserving
combined modality therapy for muscle-invasive bladder cancer: A pooled
analysis of RTOG 9906 and 0233." (Mitin T, J Clin Oncol 32, 2014 (suppl 4;
abstr 284))
• Conclusion: "There is no apparent difference in the bladder recurrence and
salvage cystectomy rates between complete and near-complete responders
as judged at the time of cystoscopic evaluation after induction phase of
bladder preserving CMT. It is appropriate to recommend that patients with
Ta or Tis after induction chemo-RT continue with bladder-sparing therapy."

16. Adds to benefit---
TECHNICAL ADVANCES
• Hyperfractionation
• Lipiodal IGRT

17. What happened to the bladders?
• Harvard- Five-, 10-, and 15-yr bladder-intact DSS rates were 60%, 45%, and
36%, respectively.
• RTOG 8802- 4-year bladder preservation 44% (60% in patients with full
course)
• RTOG 9506- 3 yr bladder preservation- 66%
• RTOG 9706- 3 yr bladder preservation- 48%
• RTOG 0233- Alive with bladder intact at 4 yrs: 73% vs 69%

18. Other modalities of bladder preservation
• Partial cystectomy
• Brachytherapy

19. • 104 patients with MIBC who underwent 3 cycles of MVAC chemotherapy
followed by
--- TURBT alone (n = 52)
--- partial cystectomy (n = 3)
--- radical cystectomy (n = 39) based on the response to neoadjuvant
chemotherapy.
• Of the 52 patients who underwent TURBT alone, 29 had either a
pathological complete response (pT0) or superficial disease after
chemotherapy.
• In addition, 44% maintained an intact bladder, with a 5-year OS rate of
67%
• Sternberg CN, Pansadoro V, Calabrò F, et al. Can patient selection for bladder preservation be based on response
to chemotherapy? Cancer. 2003;97(7):1644-1652.

20. • cT2 & cT3 disease- MVAC- TURBT
• 60 had pCR (pT0) on TURBT
• 43 had bladder-sparing surgery and 17 underwent radical cystectomy.
• The 10-year OS rate for 43 patients who underwent partial
cystectomy was 74% compared with 65% in the radical cystectomy
group.
--- Herr HW et al – JCO 98

21. • Pre op RT  surgical exploration +/- partial cystectomy  placement
of brachytherapy catheters intra-operatively.
• LRFS rate was 80% and 73% at 5 and 10 years, respectively.
• Salvage cystectomy-free survival at 5 and 10 years was 93% and 85%.
• 5- and 10-year overall survival rates were 65% and 46%.
• Cancer-specific survival at 5 and 10 years was 75% and 67%.

22. • Cases of TURBT F/B Ext RT f/b BT
• No difference in 5 yr, 10 yr OS, DSS
---- Nieuwenhuijzen et al- European urology 2005
---- Elzbieta Van Der Steen Banasik et al- Radiotherapy & oncology 2009

23. • Also very important,
TOXICITY & QUALITY OF LIFE

24. PELVIC TOXICITY
• Late pelvic toxicity with a bladder-sparing approach is low.
• On RTOG protocols 89-03, 95-06, 97-06, and 99-06, the incidence of –
-- late grade 3 genitourinary toxicities- 6%
-- gastrointestinal toxicities- 2%, respectively
(based on a median follow-up of 5 years)

25. Radical Cystectomy
• Surgical removal of the bladder, adjacent organs, and regional lymph
nodes
• In men, the bladder, prostate, seminal vesicles, proximal vas deferens,
and proximal urethra, with a margin of adipose tissue and
peritoneum, are resected en bloc.
• In women, the procedure involves an anterior pelvic exenteration to
remove the bladder, urethra, uterus, fallopian tubes, ovaries, anterior
vaginal wall, and surrounding fascia en bloc.
All this at an age of over 65 years!!

26. Diversions
• Orthotopic neobladder
• Ileal conduit (urostomy)
• Continent urinary diversion

27. • NO DIFFERENCE in the scores in any scale across these procedures.
---- Hara I et al- BJU Int 2002, Dutta SC et al J Urol 2002
• Using ileum causes malabsorption, renal acid regulation dysfunction(
hypokalemic- hypochloremic acidosis), increased oxalate abrorption,
osteoporosis, etc

28. • Erectile dysfunction-
49 sexually active men underwent radical cystectomy
33% nerve sparing procedure
Median f/u- 47 months,mean sexual health inventory scores decreased from 22
to 4 (P < .05),86% of men unable to perform vaginal penetration.
Zippe CD, Raina R, Massanyi EZ, et al. Sexual function after male
radical cystectomy in a sexually active population. Urology. 2004;64(4):682-
685; discussion 685-686

29. For bladder preservation
Massachusetts study of QOL and urodynamic studies on 71 patients with intact
bladders after chemoradiation therapy. Median follow-up of 6.3 years
• 75% of patients had normally functioning bladders based on urodynamic studies
• 85% reported no urgency or occasional urgency.
• 22% had a reduced bladder capacity
• 7 of the patients reporting significant symptoms.
• 50% had normal erectile function
Weiss et al who found that 4% of patients were dissatisfied with their bladder
function following chemoradiation therapy. (Strahlenther Onkol. 2005)

30. COMPARATIVE STUDY
Distressful symptoms and well-being after radical cystectomy and orthotopic
bladder substitution compared with a matched control population. Henningsohn L
et al. J Urol. 2002.
• 58- irradiated, 251- cystectomized, 310- general
• RT group- 74% reported little or no distress from symptoms from the urinary
tract, 38% had had intercourse the previous month and 57% (men) reported they
had ejaculated.
• Cystectomized patients, 13% had had intercourse and 0% (men) had ejaculated.
• Comparable GI toxicity
• After radical radiotherapy, 46% of the patients were willing to accept some risk
of decreased survival to become symptom-free.

31. • Quality of Life in Bladder Cancer Patients Treated with Radical
Cystectomy and Orthotopic Bladder Reconstruction versus Bladder
Preservation Protocol. Mohamed I El-Sayed et al. March 2013. J
Cancer Sci Ther
• Statistically significant difference in terms of bladder function, sexual
function and gi tract symptoms.

32. Option after recurrence exists !
• Salvage cystectomy is always an option later.
• The perioperative morbidity and mortality rates of salvage cystectomy
after previous bladder chemoradiation therapy were not very
different from primary cystectomy

33. Basics of choosing a therapeutic option
Cure rate and survival
Organ preservation
Quality of life

34. • 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.

35. • Thankyou