Adjuvant Sandwich Chemotherapy and Radiation Versus Adjuvant Chemotherapy Alone for Locally Advanced Bladder Cancer

Adjuvant Sandwich Chemotherapy and Radiation Versus Adjuvant Chemotherapy Alone for Locally Advanced Bladder Cancer

S94 International Journal of Radiation Oncology  Biology  Physics Conclusion: From 2004-2013, approximately 14% of patients in the NCDB who potent...

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S94

International Journal of Radiation Oncology  Biology  Physics

Conclusion: From 2004-2013, approximately 14% of patients in the NCDB who potentially met BPCRT criteria underwent the procedure, and these patients were significantly older and had more comorbidities than those who underwent radical cystectomy with or without chemotherapy. When matched for measurable patient characteristics, patients who underwent BPCRT demonstrated similar survival outcomes compared to those treated with radical cystectomy with or without chemotherapy. In the absence of prospective randomized studies, these results may help guide decision-making for MIBC patients considering non-surgical management options. Author Disclosure: J. Zhong: None. J. Switchenko: None. N. Jegadeesh: None. T.W. Gillespie: None. V.A. Master: None. P. Nieh: None. M. Alemozaffar: None. O. Kucuk: None. B. Carthon: None. C.P. Filson: None. A. Jani: None.

year outcome estimates for each arm and adjusted hazard ratios are shown in Table 1. Sandwich chemotherapy plus RT was associated with a statistically significant improvement in LRFS and statistically marginal benefits in DFS and OS. Treatment was well-tolerated with late grade 3 GI toxicity of 7% and 2%, respectively. Conclusion: This is the first prospective study comparing adjuvant chemotherapy plus RT vs. adjuvant chemotherapy alone in locally advanced bladder cancer. While these results need to be interpreted cautiously, adjuvant chemotherapy plus radiation appears to be welltolerated and associated with favorable cancer control outcomes. Further studies of adjuvant RT regimens are warranted. Author Disclosure: M.S. Zaghloul: None. J.P. Christodouleas: None. A. Smith: None. A. Abdalla: None. H. William: None. H.M. Khaled: None. W. Hwang: None. B.C. Baumann: None.

212 Adjuvant Sandwich Chemotherapy and Radiation Versus Adjuvant Chemotherapy Alone for Locally Advanced Bladder Cancer M.S. Zaghloul,1 J.P. Christodouleas,2,3 A. Smith,4 A. Abdalla,1 H. William,5 H.M. Khaled,1 W.T. Hwang,4 and B.C. Baumann3; 1Egyptian National Cancer Institute, Cairo, Egypt, 2Elekta, Atlanta, GA, 3University of Pennsylvania, Department of Radiation Oncology, Philadelphia, PA, 4 University of Pennsylvania, Department of Biostatistics and Epidemiology, Philadelphia, PA, 5Ahmed Maher Teaching Hospital, Cairo, Egypt Purpose/Objective(s): Adjuvant radiation for locally advanced bladder cancer has no clearly defined role in Western countries but has been a standard of care in Egypt for decades. This study was initially designed to compare adjuvant radiation therapy (RT) alone vs. sandwich chemotherapy plus RT in Egypt, but a third arm using chemotherapy alone was added later to benchmark the original trial arms against an emerging standard. The purpose of this study was to estimate the benefits of adjuvant RT by comparing cancer control outcomes of the sandwich chemotherapy plus RT and chemotherapy alone arms. Materials/Methods: The trial included patients 70 years with ECOG PS 2 with locally advanced bladder cancer and 1 high risk features who underwent radical cystectomy (RC) with negative margins at the Egyptian National Cancer Institute. High risk features included stage pT3b, grade 3, or positive nodes. Sandwich chemotherapy plus RT included sequential treatment with 2 cycles of gemcitabine/cisplatin before and after RT. RT was to 45 Gy in 1.5 Gy/fx given BID with 3D-conformal RT. Chemotherapy alone included 4 cycles of gemcitabine/cisplatin. The sandwich chemotherapy plus RT arm accrued 75 patients between 2002 and 2008. The chemotherapy alone arm accrued 45 patients from 2007-2008 with a 4:1 randomization weighted toward chemotherapy alone. Endpoints for this secondary analysis were local recurrence-free survival (LRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), overall survival (OS), and toxicity. Comparisons were adjusted for covariates that were not balanced between the arms or were associated (P < 0.1) with the outcome of interest on univariate analysis. Results: Median age was 54 (range 27 e 69), and the M:F ratio was 4:1. 53% had urothelial carcinoma, and 47% had squamous cell carcinoma/ other. Median follow-up was 21 months and 17 months for the sandwich chemotherapy plus RT and chemotherapy alone arms, respectively. The two arms were balanced except for age (mean 52 and 55, respectively, P Z 0.04) and tumor size (mean 5 cm and 6 cm, respectively, P < 0.01). Three-

Abstract 212; Table 1 Survival Endpoint LRFS DFS DMFS OS

Sequential chemo plus RT - 3 year results

Chemo alone - 3 year results

96% 68% 73% 64%

69% 56% 79% 51%

Overall Adjusted HR (P value) 0.08 0.53 1.01 0.61

(P (P (P (P

< 0.01) [ 0.07 [ 0.99) [ 0.11)

213 Concurrent Chemotherapy Improves Overall Survival in MuscleInvasive Bladder Cancer Patients Undergoing Radiation Therapy: An Analysis of the National Cancer Data Base A.M. Block,1 M.M. Harkenrider,1 E. Henry,2 E.R. Gaynor,2 and A.A. Solanki1; 1Stritch School of Medicine, Loyola University Chicago, Maywood, IL, 2Loyola University Medical Center, Maywood, IL Purpose/Objective(s): Previously reported data from multicenter phase III randomized trials support a locoregional control benefit to concurrent chemoradiation (CRT) compared to radiation therapy alone (RT) in muscle invasive bladder cancer (MIBC). These trials demonstrate trends but non-statistically significant improvement in overall survival (OS) with CRT compared to RT. In order to elucidate this benefit, we analyzed the National Cancer Data Base (NCDB) comparing CRT versus RT in MIBC. Materials/Methods: Patients with cT2-4 N0-3 M0 transitional cell MIBC treated with RT or CRT were selected. The chi-squared test was used to compare clinical, treatment, and sociodemographic covariates between both groups. The Kaplan-Meier method was used to estimate OS, and univariate analysis (UVA) was performed using the log rank test to identify the impact of covariates on OS. Multivariable analysis (MVA) was performed using the Cox Proportional Hazards model, and included all covariates with P < 0.1 on UVA. Sensitivity analysis was performed using a propensity score-matched (PSM) population. Results: Eight hundred seventy-four patients treated with radiotherapy from 2008 to 2012 met eligibility criteria; 504 (58%) patients received RT, and 370 (42%) patients received CRT. Median age was 80. CRT patients were younger (P < 0.001) and were more likely to have Charlson-Deyo comorbidity score (CDCS) of 0 (P Z 0.024). Median follow-up was 16.4 months. The 2-year OS was 42% for the entire cohort. UVA revealed CRT (2-year OS 49% vs. 36%; P < 0.001), younger age (P Z 0.011), male sex (P Z 0.016), lower CDCS (P Z 0.041), lower T-stage (P < 0.001), and radiation dose 60 Gy (P < 0.001) were associated with improved OS. MVA revealed CRT (Hazard ratio [HR] Z 0.79; 95% confidence interval [CI] Z 0.66 to 0.94; P Z 0.007) and RT dose 60 Gy (HR Z 0.49; 95% CI Z 0.41 to 0.59; P < 0.001) were associated with improved OS. T4 disease (HR Z 1.82; 95% CI Z 1.45 to 2.29; P < 0.001) was associated with worse OS, while CDCS of 2 (HR Z 1.23; 95% CI Z 0.96 to 1.59; P Z 0.094) and increasing age (HR Z 1.01; 95% CI Z 1.00 to 1.02; P Z 0.087) had trends towards worse OS. The improved OS with CRT persisted after PSM analysis. Conclusion: While randomized studies have suggested a trend towards improved OS, this population-based analysis reveals a statistically significant improvement in OS with CRT versus RT in MIBC. This survival benefit persists irrespective of radiotherapy dose, and thus CRT should be considered not only in the definitive setting, but even when using lower radiotherapy doses. Author Disclosure: A.M. Block: None. M.M. Harkenrider: None. E. Henry: None. E.R. Gaynor: None. A.A. Solanki: None.