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Common Iliac Nodal Involvement in Clinical T2 Bladder Cancer: Implications for Definitive Radiation
Oral Scientific Sessions S121
Volume 84 Number 3S Supplement 2012 was associated with an increased hazard of death from any cause (HR Z 1.26; 95% CI, 1.05 - 1.53) and from bladder cancer (HR Z 1.31; 95% CI, 0.97 - 1.77). Using the local area cystectomy rate as an instrument, instrumental variable analysis demonstrated no differences in survival between BPT and RC (death from any cause HR Z 1.06; 95% CI, 0.78 1.31; death from bladder cancer HR Z 0.94; 95% CI, 0.55 - 1.18). Simulation studies for stage misclassification yielded results consistent with those of the instrumental variable analysis. Conclusions: Instrumental variable analysis may address unmeasured confounding in observational cancer comparative effectiveness research and suggests that survival outcomes after RC and BPT are similar. Author Disclosure: J.E. Bekelman: None. E. Handorf: None. T. Guzzo: None. J. Christodouleas: None. M. Resnick: None. S. Swisher-McClure: None. D. Vaughn: None. C. Pollack: None. D. Polsky: None. N. Mitra: None.
Oral Scientific Abstract 299; Table Outcomes
5-year
10-year
OS DSS Muscle Invasive LF Non-Muscle Invasive LF DM
57% 71% 13% 31% 31%
36% 65% 14% 36% 35%
Acknowledgment: This project was supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the NCI. Author Disclosure: R.H. Mak: None. D. Hunt: None. W.U. Shipley: None. J.A. Efstathiou: None. Y. Yan: None. W.J. Tester: None. M.P. Hagan: None. D.S. Kaufman: None. N.M. Heney: None. A.L. Zietman: None.
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Long-term Outcomes After Bladder Preserving Combined Modality Therapy for Muscle-invasive Bladder Cancer: A Pooled Analysis of RTOG 8802, 8903, 9506, 9706, 9906, and 0233 R.H. Mak,1 D. Hunt,2 W.U. Shipley,3 J.A. Efstathiou,3 Y. Yan,2 W.J. Tester,4 M.P. Hagan,5 D.S. Kaufman,3 N.M. Heney,3 and A.L. Zietman3; 1Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, 2RTOG Statistical Center, Philadelphia, PA, 3 Massachusetts General Hospital, Boston, MA, 4Albert Einstein Medical Center, Philadelphia, PA, 5Virginia Commonwealth University, Richmond, VA
Common Iliac Nodal Involvement in Clinical T2 Bladder Cancer: Implications for Definitive Radiation B. Goldsmith, B. Baumann, J. He, K. Tucker, J. Bekelman, C. Deville, N. Vapiwala, T. Guzzo, B. Malkowicz, and J. Christodouleas; University of Pennsylvania Affiliated Hospitals, Philadelphia, PA
Purpose/Objective(s): Multiple prospective RTOG studies have evaluated bladder preserving combined-modality therapy (CMT) for the treatment of muscle invasive bladder cancer (MIBC). CMT includes transurethral resection and concurrent chemotherapy and radiation therapy, while reserving cystectomy for salvage. Here we report a pooled analysis of long-term outcomes from six RTOG trials. Materials/Methods: We performed a pooled analysis of 468 patients (pts) with MIBC enrolled on six RTOG bladder preserving CMT studies, including five Phase II studies: RTOG 8802, 9506, 9706, 9906, and 0233, and one Phase III study 8903. We estimated overall survival (OS) by the Kaplan-Meier method, and disease-specific survival (DSS), bladder-intact survival, local failure (LF) and distant metastasis (DM) by the cumulative incidence method. Results: The median age of the pts was 66 years (range, 34-93 years), and the majority had a performance status (PS) of 0 (89%). Transitional cell carcinoma (TCC) was the most common histology (94%). Clinical tumor stage included 61% T2, 29% T3a, 6% T3b, and 4% T4a. A complete response (CR) to CMT was observed in 72% of pts. With a median followup of 4.3 years among all pts, and 7.8 years among survivors (n Z 205), the 5-year and 10-year results were as follows: DSS was associated with CR to CMT, with 5-year DSS of 79% in pts with a CR versus 56% for non-responders (p < 0.0001). Examining outcomes by subgroups, higher clinical T-stage (T2 vs. T3/T4) was associated with decreased DSS (10-year DSS: 69% vs. 60%; p Z 0.05), and OS (10-year OS: 41% vs. 30%; p Z 0.002). Elderly (age 75) pts did not have significantly different DSS compared to younger (age 70-75 and age <70) pts (64% vs. 61% vs. 67% at 10 years, respectively). On multivariate analysis, after adjusting for age and PS, higher T-stage was associated with decreased DSS (Hazard ratio: 1.65; 95% confidence interval: 1.19-2.27; p Z 0.002). Comparing pts with TCC versus non-TCC histology (n Z 29), the 10-year DSS was 65% versus 60% (p Z 0.56), and 10-year OS was 37% versus 21% (p Z 0.11), respectively. Conclusions: Bladder preserving CMT in the multi-institutional, cooperative group setting resulted in long-term outcomes comparable to those reported in single institution series. CMT is a well-established alternative to radical cystectomy in selected pts, especially elderly pts and others at high risk of complications from surgery.
Purpose/Objective(s): In definitive radiation of clinical T2 (cT2) bladder cancer, common iliac nodal regions are not commonly treated secondary to low rates of involvement in pathologic T2 (pT2) patients and the risk of bowel toxicity. It is known, however, that cT2 patients are commonly upstaged at the time of surgery, potentially increasing the risk of pathologic common iliac node involvement. To better inform definitive radiation field design, we examined the risk and predictors of common iliac nodal involvement among cT2 patients who were treated with radical cystectomy and pelvic lymph node dissection. Materials/Methods: The study cohort included 201 patients with cT2, node-negative, transitional cell carcinoma (TCC) or TCC with variant histology and no prior history of radiation, chemotherapy, or partial cystectomy who received radical cystectomy and pelvic lymph node dissection at a single institution from 1987-2010. The pT-stage as well as node packets for the perivesicular, obturator, internal/external iliac, common iliac, and presacral regions were evaluated by a genitourinary pathologist according to a standardized protocol. Logistic regression was used to identify pre-operative characteristics predicting for common iliac involvement. Results: Among 201 cT2 patients, the proportion of patients with each pTstage was 24% pT1 (49/201), 28% pT2 (56/201), 34% pT3 (68/201), and 14% pT4 (28/201). The overall rate of nodal involvement for cT2 patients was 30% (61/201). For the entire cohort, nodal involvement by subsite was 4% (8/201) perivesicular, 21% (42/201) obturator, 3% (7/201) presacral, 16% (33/201) internal/external iliac, and 15% (30/201) common iliac. In univariate analysis, age, sex, race, BMI, smoking status, the presence of lymphovascular invasion on biopsy, and tumor histology had no statistical correlation with common iliac node involvement. The presence of bilateral hydronephrosis increased the likelihood of common iliac node positivity odds ratio 11.9 (p Z 0.0025, 95% confidence interval of 2.4 - 59.1) compared to patients with no hydronephrosis. The rate of common iliac node involvement was 57% (4/7) among patients with bilateral hydronephrosis compared to 13% (26/194) in all other patients. Conclusions: In contrast to patients with pT2 disease, patients with cT2 have substantial rates of common iliac involvement even after controlling for significant risk factors. The high rate of pathologic upstaging of these patients likely explains this finding. In the absence of more accurate clinical staging, targeting of common iliac regions during definitive radiation of patients with cT2 disease may be warranted. Author Disclosure: B. Goldsmith: None. B. Baumann: None. J. He: None. K. Tucker: None. J. Bekelman: None. C. Deville: None. N. Vapiwala: None. T. Guzzo: None. B. Malkowicz: None. J. Christodouleas: None.
Volume 84 Number 3S Supplement 2012 was associated with an increased hazard of death from any cause (HR Z 1.26; 95% CI, 1.05 - 1.53) and from bladder cancer (HR Z 1.31; 95% CI, 0.97 - 1.77). Using the local area cystectomy rate as an instrument, instrumental variable analysis demonstrated no differences in survival between BPT and RC (death from any cause HR Z 1.06; 95% CI, 0.78 1.31; death from bladder cancer HR Z 0.94; 95% CI, 0.55 - 1.18). Simulation studies for stage misclassification yielded results consistent with those of the instrumental variable analysis. Conclusions: Instrumental variable analysis may address unmeasured confounding in observational cancer comparative effectiveness research and suggests that survival outcomes after RC and BPT are similar. Author Disclosure: J.E. Bekelman: None. E. Handorf: None. T. Guzzo: None. J. Christodouleas: None. M. Resnick: None. S. Swisher-McClure: None. D. Vaughn: None. C. Pollack: None. D. Polsky: None. N. Mitra: None.
Oral Scientific Abstract 299; Table Outcomes
5-year
10-year
OS DSS Muscle Invasive LF Non-Muscle Invasive LF DM
57% 71% 13% 31% 31%
36% 65% 14% 36% 35%
Acknowledgment: This project was supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the NCI. Author Disclosure: R.H. Mak: None. D. Hunt: None. W.U. Shipley: None. J.A. Efstathiou: None. Y. Yan: None. W.J. Tester: None. M.P. Hagan: None. D.S. Kaufman: None. N.M. Heney: None. A.L. Zietman: None.
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300
Long-term Outcomes After Bladder Preserving Combined Modality Therapy for Muscle-invasive Bladder Cancer: A Pooled Analysis of RTOG 8802, 8903, 9506, 9706, 9906, and 0233 R.H. Mak,1 D. Hunt,2 W.U. Shipley,3 J.A. Efstathiou,3 Y. Yan,2 W.J. Tester,4 M.P. Hagan,5 D.S. Kaufman,3 N.M. Heney,3 and A.L. Zietman3; 1Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, 2RTOG Statistical Center, Philadelphia, PA, 3 Massachusetts General Hospital, Boston, MA, 4Albert Einstein Medical Center, Philadelphia, PA, 5Virginia Commonwealth University, Richmond, VA
Common Iliac Nodal Involvement in Clinical T2 Bladder Cancer: Implications for Definitive Radiation B. Goldsmith, B. Baumann, J. He, K. Tucker, J. Bekelman, C. Deville, N. Vapiwala, T. Guzzo, B. Malkowicz, and J. Christodouleas; University of Pennsylvania Affiliated Hospitals, Philadelphia, PA
Purpose/Objective(s): Multiple prospective RTOG studies have evaluated bladder preserving combined-modality therapy (CMT) for the treatment of muscle invasive bladder cancer (MIBC). CMT includes transurethral resection and concurrent chemotherapy and radiation therapy, while reserving cystectomy for salvage. Here we report a pooled analysis of long-term outcomes from six RTOG trials. Materials/Methods: We performed a pooled analysis of 468 patients (pts) with MIBC enrolled on six RTOG bladder preserving CMT studies, including five Phase II studies: RTOG 8802, 9506, 9706, 9906, and 0233, and one Phase III study 8903. We estimated overall survival (OS) by the Kaplan-Meier method, and disease-specific survival (DSS), bladder-intact survival, local failure (LF) and distant metastasis (DM) by the cumulative incidence method. Results: The median age of the pts was 66 years (range, 34-93 years), and the majority had a performance status (PS) of 0 (89%). Transitional cell carcinoma (TCC) was the most common histology (94%). Clinical tumor stage included 61% T2, 29% T3a, 6% T3b, and 4% T4a. A complete response (CR) to CMT was observed in 72% of pts. With a median followup of 4.3 years among all pts, and 7.8 years among survivors (n Z 205), the 5-year and 10-year results were as follows: DSS was associated with CR to CMT, with 5-year DSS of 79% in pts with a CR versus 56% for non-responders (p < 0.0001). Examining outcomes by subgroups, higher clinical T-stage (T2 vs. T3/T4) was associated with decreased DSS (10-year DSS: 69% vs. 60%; p Z 0.05), and OS (10-year OS: 41% vs. 30%; p Z 0.002). Elderly (age 75) pts did not have significantly different DSS compared to younger (age 70-75 and age <70) pts (64% vs. 61% vs. 67% at 10 years, respectively). On multivariate analysis, after adjusting for age and PS, higher T-stage was associated with decreased DSS (Hazard ratio: 1.65; 95% confidence interval: 1.19-2.27; p Z 0.002). Comparing pts with TCC versus non-TCC histology (n Z 29), the 10-year DSS was 65% versus 60% (p Z 0.56), and 10-year OS was 37% versus 21% (p Z 0.11), respectively. Conclusions: Bladder preserving CMT in the multi-institutional, cooperative group setting resulted in long-term outcomes comparable to those reported in single institution series. CMT is a well-established alternative to radical cystectomy in selected pts, especially elderly pts and others at high risk of complications from surgery.
Purpose/Objective(s): In definitive radiation of clinical T2 (cT2) bladder cancer, common iliac nodal regions are not commonly treated secondary to low rates of involvement in pathologic T2 (pT2) patients and the risk of bowel toxicity. It is known, however, that cT2 patients are commonly upstaged at the time of surgery, potentially increasing the risk of pathologic common iliac node involvement. To better inform definitive radiation field design, we examined the risk and predictors of common iliac nodal involvement among cT2 patients who were treated with radical cystectomy and pelvic lymph node dissection. Materials/Methods: The study cohort included 201 patients with cT2, node-negative, transitional cell carcinoma (TCC) or TCC with variant histology and no prior history of radiation, chemotherapy, or partial cystectomy who received radical cystectomy and pelvic lymph node dissection at a single institution from 1987-2010. The pT-stage as well as node packets for the perivesicular, obturator, internal/external iliac, common iliac, and presacral regions were evaluated by a genitourinary pathologist according to a standardized protocol. Logistic regression was used to identify pre-operative characteristics predicting for common iliac involvement. Results: Among 201 cT2 patients, the proportion of patients with each pTstage was 24% pT1 (49/201), 28% pT2 (56/201), 34% pT3 (68/201), and 14% pT4 (28/201). The overall rate of nodal involvement for cT2 patients was 30% (61/201). For the entire cohort, nodal involvement by subsite was 4% (8/201) perivesicular, 21% (42/201) obturator, 3% (7/201) presacral, 16% (33/201) internal/external iliac, and 15% (30/201) common iliac. In univariate analysis, age, sex, race, BMI, smoking status, the presence of lymphovascular invasion on biopsy, and tumor histology had no statistical correlation with common iliac node involvement. The presence of bilateral hydronephrosis increased the likelihood of common iliac node positivity odds ratio 11.9 (p Z 0.0025, 95% confidence interval of 2.4 - 59.1) compared to patients with no hydronephrosis. The rate of common iliac node involvement was 57% (4/7) among patients with bilateral hydronephrosis compared to 13% (26/194) in all other patients. Conclusions: In contrast to patients with pT2 disease, patients with cT2 have substantial rates of common iliac involvement even after controlling for significant risk factors. The high rate of pathologic upstaging of these patients likely explains this finding. In the absence of more accurate clinical staging, targeting of common iliac regions during definitive radiation of patients with cT2 disease may be warranted. Author Disclosure: B. Goldsmith: None. B. Baumann: None. J. He: None. K. Tucker: None. J. Bekelman: None. C. Deville: None. N. Vapiwala: None. T. Guzzo: None. B. Malkowicz: None. J. Christodouleas: None.