Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer
1. Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer Jason A. Efstathiou, MD, DPhil Assistant Professor of Radiation Oncology Massachusetts General Hospital Harvard Medical School
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4. Radiation Alone with Salvage Cystectomy vs Preop RT and Immediate Cystectomy ( a) SD Cutler, National Cancer Institute, unpublished observations, 1983 5-year survival data from 4 randomized trials comparing preoperative radiation therapy (40-50Gy) with immediate cystectomy to radiation therapy alone (60Gy) with salvage cystectomy for recurrence Study No. of patients 5-year Survival with Pre-op RT and cystectomy % 5-year Survival with RT and salvage cystectomy % Statistical Significance Notes Urologic Cooperative Group, UK 189 39 28 None Danish National Cancer Group 183 29 23 None National Bladder Cancer Group (a) 72 27 40 None MD Anderson Cancer Center 67 45 22 Significant Large T3 tumors included
23. Meta-Analysis of Neoadjuvant Chemotherapy in Invasive Bladder Cancer Phase III series with RADIATION THERAPY ( A total of 526 patients ) European Urology 48: 202-206, 2005 P=0.334
24. What is the importance of an aggressive TURBT for “Cystectomy Avoidance”? “ The TURBT must be done with the determination to resect all visible tumor. Nothing less will suffice.” NM Heney et al NATURE Rev Clin Oncol 2009
25. All TURBT TURBT patients complete not complete p value Number 343 227 116 CR rate 72% 79% 57% <0.001 5 year outcomes Overall Survival 52% 57% 43% 0.003 DSS 64% 68% 56% 0.03 % undergoing cystectomy TOTAL 29% 22% 42% <0.001 Immediate (non-CR) 17% 11% 29% Salvage 12% 11% 13% Long-term MGH Experience 1986-2006 The value of complete TURBT Efstathiou et al Eur Urol 2011
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27. How does bladder preservation by combined modality therapy compare with radical cystectomy ?
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29. Survival after curative therapy Stage Number 5 year OS 10 year OS Cystectomy USC 2001 pT2-4a 633 48% 32% MSKCC 2001 pT2-4a 181 36% 27% SWOG 2003 cT2-3 303 49% - Chemo-RT RTOG 1998 cT2-4a 123 49% - Erlangen 2002 cT2-4 326 45% 29% MGH 2011 cT2-4a 348 52% 35%
32. MRC “SPARE” Bladder Protocol Life and death of spare (selective bladder preservation against radical excision): reflections on why the spare trial closed. Huddart et al BJU Int 2010
51. QoL due to urinary symptoms after TURBT and chemoRT If you were to spend the rest of your life with your urinary condition the way it is now, how would you feel about that? Weiss et al 2005 delighted pleased mostly satisfied mixed – about equally satisfied and dissatis- fied mostly dissatisfied unhappy terrible 18.5% 51.7% 17.2% 9.1 % 0.8% 2 % 0.7%
52. 2 comparative cross-sectional studies available: Trento, Italy 1996 Incontinent diversion vs chemo-RT Karolinska, Sweden 2002 Incont. and cont. diversions vs RT vs controls Quality of life after treatment of invasive bladder cancer: Cystectomy or organ-conserving therapy
53. QOL advantage to chemo-RT: psychologic adjustment physical well-being energy sexual function urinary function QOL equivalence chemo-RT vs surgery: Social functioning Bowel function Quality of life after treatment of invasive bladder cancer: Cystectomy or organ-conserving therapy
54. Henningsohn et al 2002 Urinary function : RT - 74% little or no urinary symptom distress Sexual function : RT - 38% intercourse previous month Cyst - 13% intercourse previous month Quality of life after treatment of invasive bladder cancer: Cystectomy or organ-conserving therapy
55. Henningsohn et al 2002 Bowel function : mod or much distress RT 32% Cystectomy 24% Controls 9% Sig NS Quality of life after treatment of invasive bladder cancer: Cystectomy or organ-conserving therapy
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57. Morbidity of primary radical cystectomy Donat et al 2009 1142 RCs at MSKCC 1995-2005 Prospectively captured morbidity data Reported complications within 90 days Graded 0-5 on modified Clavien Scale
58. Morbidity of primary radical cystectomy Donat et al 2009 64% More than 1 complication 13% Grade 3-5 26% Readmissions 2% 90 day mortality Donat et al Eur Urol, 2009
59. Grade Total <30 days <90 days MSKCC Morbidity of salvage radical cystectomy at the MGH Eswara et al J Urol 2011 (in press) 1 72 39% 53 48% 58 45% 26% 2 55 30% 42 38% 48 38% 62% 3 52 28% 11 10% 18 14% 11% 4 3 2% 2 2% 2 2% 0% 5 2 1% 2 2% 2 2% 2%
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66. Treatment/ Comparison Evidence Level of Evidence Grade of Recommendation RT alone vs 40Gy+Cystectomy 3 of 4 RCTs report similar survival 1b A ChemoRT vs RT alone 2 RCTs report significant improvement in bladder tumor eradication 1b A Neoadjuvant CT with RT or ChemoRT 3 RCTs and 1 meta-analysis report no benefit 1a A ChemoRT preserves good bladder function 3 QOL studies and RTOG protocols report good tolerance 2a B Complete TURBT with ChemoRT 3 reports (1 phase III, 2 phase II) show benefit 2a B Predictive Biomarkers of outcome after RT MRE 11 expression predicts improved CSS (1 study) 2b B Trimodality therapy vs immediate cystectomy Comparison of 3 contemporary series of each report similar 5- and 10-yr survival 3 C
Editor's Notes
A CR is significantly associated with DSS and thus offers a potential early endpoint for biomarker evaluations
Personalized medicine – apply to individuals in a patient centered way Large observational studies and databases and pooled trial results can be used to learn more about subgroups of patients who might benefit from certain therapies Need for surrogate markers for outcome and even incorporate metrics for patient preference (BCT)
In addition to up-date on late toxicity we wanted to assess QoL and therefor we used the Quality of life Question of the IPS Score Nothing can substitute the own bladder
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