- Email: [email protected]
Development and Validation of Contouring Guidelines for Postcystectomy Adjuvant Radiation of Bladder Cancer
S24
International Journal of Radiation Oncology Biology Physics
51
Materials/Methods: A PubMed literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) literature selection process. All prospective and retrospective studies available in full text from January 1990 to December 2013, involving more than 20 patients with nonmetastatic MIBC stage T2e4a N0 M0, treated with RC ( NAC) or TMT, and reporting 5-year overall survival (OS) rates, were selected. Results: A total of 10,265 and 3,131 patients in the RC ( NAC) and TMT groups, respectively, were identified. The median 5-year OS was 52% in the former group and 57% in the latter group (P Z .04), respectively. The median 5-year OS rates of patients who received RC alone or RC + NAC were 51% (P Z .02) and 53% (P Z .38), respectively. Multivariate analysis confirmed TMT as a significant prognostic variable. Conclusion: Compared with RC ( NAC), TMT is associated with a survival advantage in the management of MIBC. The addition of NAC may improve the RC outcome in some subgroups of patients with a higher probability of micrometastases. Appropriate randomized controlled trials are warranted to confirm these findings and define the role of the organ preservation strategy in this setting. Author Disclosure: S. Arcangeli: None.
Conditional Survival Probabilities Following Bladder Preservation for Patients With Muscle-Invasive Bladder Cancer M.V. Mishra,1 T. Dan,2 and A.V. Louie3; 1University of Maryland, Baltimore, MD, 2Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, 3London Regional Cancer Program, London, ON, Canada Purpose/Objective(s): Trimodality treatment for patients with muscleinvasive bladder cancer (MIBC) has been shown to produce comparable outcomes to those of cystectomy with the benefit of organ preservation. Although overall and disease-specific survival rates following bladder preservation are well described, the relevance of such data diminishes over time for cancer survivors. Conditional survival (CS) statistics provide more relevant survival estimates for long-term survivors in follow-up. Although CS following radical cystectomy has been described, to our knowledge it has not been reported in the context of bladder preservation. The primary aim of this study was to analyze CS estimates for patients undergoing bladder preservation therapy. A secondary study objective was to determine if factors prognostic of survival at the time of diagnosis remain relevant in survivorship. Materials/Methods: Patients diagnosed with nonmetastatic, MIBC between 1998 and 2011 were identified from the Surveillance, Epidemiology, and End Results Database. Data on patient and tumor characteristics, as well as initial treatment with surgery and radiation therapy (RT), were extracted. Overall survival (OS) and cause-specific survival (CSS) were calculated using the Kaplan-Meier method. Prognostic factors associated with survival at different time points from diagnosis were analyzed using multivariable Cox proportional hazards modeling (MVA). Results: A total of 3488 patients with nonmetastatic MIBC who underwent transurethral resection of tumor (TURBT) followed by RT were identified. The median age at diagnosis was 79 years, and 86% of patients were White. The 1-, 3-, and 5-year OS estimates from the time of diagnosis were 62%, 31%, and 35%, respectively. The 1-, 3-, and 5-year CSS estimates from the time of diagnosis were 22%, 71%, and 41%, respectively. Given a 1-year (n Z 2000), 3-year (n Z 803), and 5-year (n Z 432) survivorship, a patient’s chance of surviving an additional 5 years increased by +8% (30%), + 22% (44%), and +24% (46%), respectively, whereas 5-year CSS increased by +12% (47%), +36% (71%), and +44% (79%). Prognostic factors associated with all-cause mortality at the time of diagnosis on MVA were increasing age, black race, and stage (P < .05). However, after 5 years of survivorship, increasing age was the only factor associated with survival on MVA (hazard ratio Z 1.08, P < .001). Conclusion: These data provide important information that can be used to counsel bladder preservation therapy patients on how their prognosis may change over time and may be incorporated into survivorship care plans. This information may also be used by clinicians to further inform management decisions regarding long-term follow-up and cystoscopic surveillance based on changing survival expectations over time. Author Disclosure: M.V. Mishra: None. T. Dan: None. A.V. Louie: None.
52 A Systematic Review of Radical Cystectomy Versus Organ Preserving Trimodal Therapy in Muscle-Invasive Bladder Cancer S. Arcangeli; San Camillo-Forlanini Hospital, Rome, Italy Purpose/Objective(s): To compare 5-year overall survival (OS) rates from retrospective and prospective studies of radical cystectomy (RC) neoadjuvant chemotherapy (NAC) and combined trimodal therapy (TMT), that is, concurrent delivery of chemotherapy and radiation therapy after a transurethral resection of bladder tumor (TURBT), in the management of nonmetastatic muscle-invasive bladder cancer (MIBC), respectively.
53 Development and Validation of Contouring Guidelines for Postcystectomy Adjuvant Radiation of Bladder Cancer J.P. Christodouleas,1 B.C. Baumann,1 W.R. Bosch,2 A. Bahl,3 A. Birtle,4 R. Breau,5 A. Challapalli,6 A.J. Chang,7 A. Choudhury,8 S. Daneshmand,9 A.S. Feldman,10 T. Guzzo,1 S. Hilman,11 A. Jani,12 B. Malkowicz,1 V.A. Master,13 A. Mitra,14 S. Porten,7 J.A. Efstathiou,15 and L. Eapen5; 1 University of Pennsylvania, Philadelphia, PA, 2Washington University School of Medicine, St. Louis, MO, 3UHBristol NHS Foundation Trust, Bristol, United Kingdom, 4Royal Preston Hospital, Preston, United Kingdom, 5The Ottawa Hospital, Ottawa, ON, Canada, 6Imperial College, London, London, United Kingdom, 7University of California, San Francisco, San Francisco, CA, 8The Christie NHS Foundation Trust, Manchester, United Kingdom, 9University of Southern California, Los Angeles, CA, 10Massachusetts General Hospital, Boston, MA, 11Weston General Hospital, Weston-Super-Mare, United Kingdom, 12Winship Cancer Institute of Emory University, Atlanta, GA, 13Emory University, Atlanta, GA, 14University College London, London, United Kingdom, 15 Massachusetts General Hospital, Harvard Medical School, Boston, MA Purpose/Objective(s): Several organizations are considering studying the role of adjuvant radiation for bladder cancer patients at elevated risk of locoregional failure (LF). However, the clinical target volumes (CTVs) and organs at risk (OARs) for this treatment have not been defined in detail. The purpose of this project was to define multi-institutional consensus CTVs and OARs for male and female bladder cancer patients undergoing adjuvant radiation in clinical trials. Materials/Methods: We convened a multidisciplinary group of bladder cancer specialists representing 9 institutions in 3 countries. Five radiation oncologists and 7 urologists participated in the development of the proposed contours, and another 5 radiation oncologists participated in their validation. The development group proposed initial language for the CTVs and OARs and contoured according to these on CT scans of a male and female patient who had prior radical cystectomies. We required that initial contours for the CTVs have input from at least 1 urologist at each participating institution. Using the binomial maximum-likelihood estimates method, we generated 95% level initial development group contours. We evaluated the contours for level of agreement using the Landis and Koch interpretation of the K statistic. Based on the initial contouring, the development group updated its descriptions of the CTVs and OARs. To determine whether the updated language produces consistent contours, the cystectomy bed contour was redrawn on the male and female CT sets by an additional 5 radiation oncologists.
Volume 93 Number 3S Supplement 2015
Oral Scientific Sessions
Oral Scientific Abstracts 53; Table 1. K-statistic Male Female
Cyst bed
Pelvic LN
Bowel space
Rectum
Bone marrow
Urinary diversion
0.59 0.55
0.68 0.58
0.64 0.67
0.55 0.50
0.84 0.81
0.43 0.50
Results: The development group proposed that patients at elevated risk for LF but negative surgical margins should be treated to pelvic lymph node regions alone, including the internal iliac, external iliac, distal common iliac, and presacral nodes. In contrast, it is proposed that patients with positive surgical margins be treated to both the pelvic lymph nodes and the cystectomy bed. The development group proposed that the following OARs be identified: rectum, bowel space, bone marrow, and urinary diversion. The level of agreement for the initial CTVs and OARs from the development group varied substantially (Table). Consensus language to describe CTV and OAR structures where the initial contours varied was successfully developed. Contours and feedback from the validation group are being analyzed. Conclusion: Initial descriptions of CTVs and OARs have been successfully developed. External validation and feedback are pending. The results of this work will be applicable to clinical trials of adjuvant radiation in bladder cancer. Author Disclosure: J.P. Christodouleas: None. B.C. Baumann: None. W.R. Bosch: None. A. Bahl: None. A. Birtle: None. R. Breau: None. A. Challapalli: None. A.J. Chang: None. A. Choudhury: None. S. Daneshmand: None. A.S. Feldman: None. T. Guzzo: None. S. Hilman: None. A. Jani: None. B. Malkowicz: None. V.A. Master: None. A. Mitra: None. S. Porten: None. J.A. Efstathiou: None. L. Eapen: None.
54 Factors Associated With Regional Recurrence Following Lymphadenectomy for Penile Squamous Cell Carcinoma: One Institutions Experience J. Reddy,1 L.B. Levy,2 C.A. Pettaway,1 L. Pagliaro,1 P. Tamboli,1 P. Rao,1 I. Jayaratna,1 and K.E. Hoffman1; 1MD Anderson Cancer Center, Houston, TX, 2The University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Factors associated with regional recurrence (RR) following lymphadenectomy for penile cancer were assessed to determine which patients might benefit from adjuvant therapy. Materials/Methods: Men who underwent lymphadenectomy for penile squamous cell carcinoma from 1978 to 2014 were identified from an institutional database. Kaplan-Meier curves estimated time to RR calculated from the date of lymphadenectomy. Cox proportional hazards models evaluated the association between RR and patient and tumor characteristics. Backward selection with P-value cutoff of .05 selected covariates into the multivariate model. Results: A total of 173 men underwent lymphadenectomy and did not receive adjuvant radiation therapy. Of these patients, 50.3% underwent inguinal lymphadenectomy, and 49.1% underwent inguinal and pelvic lymphadenectomy. A further 26% of patients received neoadjuvant chemotherapy, and 8.1% received adjuvant chemotherapy. Median patient age was 63 years (range, 23e93), and median follow-up for living patients was 4.1 years. Of 29 men who experienced RR following lymphadenectomy, 21 of them developed isolated RR. Among men who failed, median time to RR was 4.9 months (IQR, 3.8e10.8). Three and 5-year cumulative incidence of RR were 17.7% and 18.7%, respectively. On univariate analysis, clinical N3 disease (P < .001), the presence of extranodal extension at lymphadenectomy (ENE, P < .001), and involvement of >3 nodes at lymphadenectomy (P < .001) were associated with RR. Threeyear RR was 42.7% in men with ENE and 8.6% in men without ENE. For men with >3 involved nodes, 3-year RR was 58.5% versus 9.8% in men with <3 involved nodes. Three-year RR for men with cN0, cN1, cN2, and cN3 disease was 5.6%, 21.2%, 17.6%, and 41.4%, respectively. On multivariate analysis, >3 pathologically involved nodes (AHR Z 8.53,
S25
95% CI: 3.5e20.69; P < .0001), ENE (AHR Z 7.30, 95% CI: 3.00e17.77; P < .001), and lack of adjuvant chemotherapy (AHR Z 8.08, 95% CI: 1.71e38.07; P Z .008) were associated with RR. Median survival for men who experienced RR was 11.3 months compared to 15.3 years for men who did not develop RR. Conclusion: The presence >3 lymph nodes after lymphadenectomy, ENE, and lack of adjuvant chemotherapy were associated with increased risk of RR. Since RR portends a dismal prognosis with few salvage options, men with these adverse factors should be considered for adjuvant therapy, including radiation therapy, to reduce RR. Author Disclosure: J. Reddy: None. L.B. Levy: None. C.A. Pettaway: None. L. Pagliaro: None. P. Tamboli: None. P. Rao: None. I. Jayaratna: None. K.E. Hoffman: Research Grant; ASTRO. Consultant; Vanderbilt University. Science Workshops Subcommittee; ASTRO. Best Practices Subcommittee; ASTRO.
55 Patterns of Care and Propensity Score–Adjusted Survival in Stage I Testicular Seminoma S.M. Glaser,1 J. Vargo,1 G. Balasubramani,2 and S. Beriwal1; 1University of Pittsburgh Cancer Institute, Pittsburgh, PA, 2University of Pittsburgh School of Public Health, Pittsburgh, PA Purpose/Objective(s): The majority of stage I seminoma patients are cured by orchiectomy alone, leading many to advocate for active surveillance (AS) over adjuvant treatment (AT). This concept has not been tested in a prospective, randomized trial. AT can be either radiation therapy (RT) or chemotherapy (CT). We sought to analyze the factors affecting adjuvant treatment decisions and resulting survival outcomes using a population-based cohort. Materials/Methods: We identified 33,094 stage I seminoma patients following orchiectomy from 1998 to 2012 from the National Cancer Database. Factors affecting treatment selection (AS vs. AT) were studied using a parsimonious multivariate logistic regression model. Propensity scores for treatment decision were generated and incorporated into a multivariate Cox regression analysis of overall survival. This process was then repeated within the AT cohort for factors predictive for CT versus RT. Results: Only 33% received AS and 65% received AT (89% RT and 11% CT). From 1998 to 2012, the proportion receiving AS increased from 23% to 60%, while RT utilization decreased from 73% to 21%, and CT utilization increased from 2% to 17%. Factors associated with AS utilization over ATon multivariate analysis included later year of diagnosis, lower T stage, smaller tumors, negative surgical margins, pathologic examination of lymph nodes, lower facility volume, treatment at an academic center, increasing distance from facility, being uninsured, and geographic location. Factors associated with RT utilization over CT on multivariate analysis included earlier year of diagnosis, non-Hispanic ethnicity, private insurance, nonacademic center, lower T stage, closer distance to facility, no pathologic lymph node examination, and geographic location. At a median follow-up of 67 months (IQR Z 36e108 mo), the 10-yr overall survival (OS) was higher for AT than AS at 95.0% (95% CI Z 94.6e95.4) versus 93.4% (95% CI Z 92.6e94.2) with a propensity score adjusted hazard ratio (HR) of 0.61 (95% CI Z 0.48e.76, P < .0001). This remained significant with a 6-month conditional landmark analysis (HR Z 0.62, 95% CI Z 0.49e0.78). Increased OS with treatment persisted across subset analysis including T stage, age, LVSI, and tumor size. The 10-yr OS was similar between CT and RT at 92.5% (95% CI Z 89.5e95.5) versus 95.1% (95% CI Z 94.7e95.5) with a propensity score adjusted HR of 0.97 (95% CI Z 0.59e1.61, P Z .91). Conclusion: Consistent with National Comprehensive Cancer Network guidelines, there has been a significant increase in use of AS for stage I seminoma, influenced by both sociodemographic and clinicopathologic factors. Between AT options, there has been a significant increase in use of CT mirrored by a decline in the use of RT. While overall survival remains high for all three treatment strategies, AT appears to be associated with a small absolute survival advantage over AS. Author Disclosure: S.M. Glaser: None. J. Vargo: None. G. Balasubramani: None. S. Beriwal: None.
International Journal of Radiation Oncology Biology Physics
51
Materials/Methods: A PubMed literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) literature selection process. All prospective and retrospective studies available in full text from January 1990 to December 2013, involving more than 20 patients with nonmetastatic MIBC stage T2e4a N0 M0, treated with RC ( NAC) or TMT, and reporting 5-year overall survival (OS) rates, were selected. Results: A total of 10,265 and 3,131 patients in the RC ( NAC) and TMT groups, respectively, were identified. The median 5-year OS was 52% in the former group and 57% in the latter group (P Z .04), respectively. The median 5-year OS rates of patients who received RC alone or RC + NAC were 51% (P Z .02) and 53% (P Z .38), respectively. Multivariate analysis confirmed TMT as a significant prognostic variable. Conclusion: Compared with RC ( NAC), TMT is associated with a survival advantage in the management of MIBC. The addition of NAC may improve the RC outcome in some subgroups of patients with a higher probability of micrometastases. Appropriate randomized controlled trials are warranted to confirm these findings and define the role of the organ preservation strategy in this setting. Author Disclosure: S. Arcangeli: None.
Conditional Survival Probabilities Following Bladder Preservation for Patients With Muscle-Invasive Bladder Cancer M.V. Mishra,1 T. Dan,2 and A.V. Louie3; 1University of Maryland, Baltimore, MD, 2Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, 3London Regional Cancer Program, London, ON, Canada Purpose/Objective(s): Trimodality treatment for patients with muscleinvasive bladder cancer (MIBC) has been shown to produce comparable outcomes to those of cystectomy with the benefit of organ preservation. Although overall and disease-specific survival rates following bladder preservation are well described, the relevance of such data diminishes over time for cancer survivors. Conditional survival (CS) statistics provide more relevant survival estimates for long-term survivors in follow-up. Although CS following radical cystectomy has been described, to our knowledge it has not been reported in the context of bladder preservation. The primary aim of this study was to analyze CS estimates for patients undergoing bladder preservation therapy. A secondary study objective was to determine if factors prognostic of survival at the time of diagnosis remain relevant in survivorship. Materials/Methods: Patients diagnosed with nonmetastatic, MIBC between 1998 and 2011 were identified from the Surveillance, Epidemiology, and End Results Database. Data on patient and tumor characteristics, as well as initial treatment with surgery and radiation therapy (RT), were extracted. Overall survival (OS) and cause-specific survival (CSS) were calculated using the Kaplan-Meier method. Prognostic factors associated with survival at different time points from diagnosis were analyzed using multivariable Cox proportional hazards modeling (MVA). Results: A total of 3488 patients with nonmetastatic MIBC who underwent transurethral resection of tumor (TURBT) followed by RT were identified. The median age at diagnosis was 79 years, and 86% of patients were White. The 1-, 3-, and 5-year OS estimates from the time of diagnosis were 62%, 31%, and 35%, respectively. The 1-, 3-, and 5-year CSS estimates from the time of diagnosis were 22%, 71%, and 41%, respectively. Given a 1-year (n Z 2000), 3-year (n Z 803), and 5-year (n Z 432) survivorship, a patient’s chance of surviving an additional 5 years increased by +8% (30%), + 22% (44%), and +24% (46%), respectively, whereas 5-year CSS increased by +12% (47%), +36% (71%), and +44% (79%). Prognostic factors associated with all-cause mortality at the time of diagnosis on MVA were increasing age, black race, and stage (P < .05). However, after 5 years of survivorship, increasing age was the only factor associated with survival on MVA (hazard ratio Z 1.08, P < .001). Conclusion: These data provide important information that can be used to counsel bladder preservation therapy patients on how their prognosis may change over time and may be incorporated into survivorship care plans. This information may also be used by clinicians to further inform management decisions regarding long-term follow-up and cystoscopic surveillance based on changing survival expectations over time. Author Disclosure: M.V. Mishra: None. T. Dan: None. A.V. Louie: None.
52 A Systematic Review of Radical Cystectomy Versus Organ Preserving Trimodal Therapy in Muscle-Invasive Bladder Cancer S. Arcangeli; San Camillo-Forlanini Hospital, Rome, Italy Purpose/Objective(s): To compare 5-year overall survival (OS) rates from retrospective and prospective studies of radical cystectomy (RC) neoadjuvant chemotherapy (NAC) and combined trimodal therapy (TMT), that is, concurrent delivery of chemotherapy and radiation therapy after a transurethral resection of bladder tumor (TURBT), in the management of nonmetastatic muscle-invasive bladder cancer (MIBC), respectively.
53 Development and Validation of Contouring Guidelines for Postcystectomy Adjuvant Radiation of Bladder Cancer J.P. Christodouleas,1 B.C. Baumann,1 W.R. Bosch,2 A. Bahl,3 A. Birtle,4 R. Breau,5 A. Challapalli,6 A.J. Chang,7 A. Choudhury,8 S. Daneshmand,9 A.S. Feldman,10 T. Guzzo,1 S. Hilman,11 A. Jani,12 B. Malkowicz,1 V.A. Master,13 A. Mitra,14 S. Porten,7 J.A. Efstathiou,15 and L. Eapen5; 1 University of Pennsylvania, Philadelphia, PA, 2Washington University School of Medicine, St. Louis, MO, 3UHBristol NHS Foundation Trust, Bristol, United Kingdom, 4Royal Preston Hospital, Preston, United Kingdom, 5The Ottawa Hospital, Ottawa, ON, Canada, 6Imperial College, London, London, United Kingdom, 7University of California, San Francisco, San Francisco, CA, 8The Christie NHS Foundation Trust, Manchester, United Kingdom, 9University of Southern California, Los Angeles, CA, 10Massachusetts General Hospital, Boston, MA, 11Weston General Hospital, Weston-Super-Mare, United Kingdom, 12Winship Cancer Institute of Emory University, Atlanta, GA, 13Emory University, Atlanta, GA, 14University College London, London, United Kingdom, 15 Massachusetts General Hospital, Harvard Medical School, Boston, MA Purpose/Objective(s): Several organizations are considering studying the role of adjuvant radiation for bladder cancer patients at elevated risk of locoregional failure (LF). However, the clinical target volumes (CTVs) and organs at risk (OARs) for this treatment have not been defined in detail. The purpose of this project was to define multi-institutional consensus CTVs and OARs for male and female bladder cancer patients undergoing adjuvant radiation in clinical trials. Materials/Methods: We convened a multidisciplinary group of bladder cancer specialists representing 9 institutions in 3 countries. Five radiation oncologists and 7 urologists participated in the development of the proposed contours, and another 5 radiation oncologists participated in their validation. The development group proposed initial language for the CTVs and OARs and contoured according to these on CT scans of a male and female patient who had prior radical cystectomies. We required that initial contours for the CTVs have input from at least 1 urologist at each participating institution. Using the binomial maximum-likelihood estimates method, we generated 95% level initial development group contours. We evaluated the contours for level of agreement using the Landis and Koch interpretation of the K statistic. Based on the initial contouring, the development group updated its descriptions of the CTVs and OARs. To determine whether the updated language produces consistent contours, the cystectomy bed contour was redrawn on the male and female CT sets by an additional 5 radiation oncologists.
Volume 93 Number 3S Supplement 2015
Oral Scientific Sessions
Oral Scientific Abstracts 53; Table 1. K-statistic Male Female
Cyst bed
Pelvic LN
Bowel space
Rectum
Bone marrow
Urinary diversion
0.59 0.55
0.68 0.58
0.64 0.67
0.55 0.50
0.84 0.81
0.43 0.50
Results: The development group proposed that patients at elevated risk for LF but negative surgical margins should be treated to pelvic lymph node regions alone, including the internal iliac, external iliac, distal common iliac, and presacral nodes. In contrast, it is proposed that patients with positive surgical margins be treated to both the pelvic lymph nodes and the cystectomy bed. The development group proposed that the following OARs be identified: rectum, bowel space, bone marrow, and urinary diversion. The level of agreement for the initial CTVs and OARs from the development group varied substantially (Table). Consensus language to describe CTV and OAR structures where the initial contours varied was successfully developed. Contours and feedback from the validation group are being analyzed. Conclusion: Initial descriptions of CTVs and OARs have been successfully developed. External validation and feedback are pending. The results of this work will be applicable to clinical trials of adjuvant radiation in bladder cancer. Author Disclosure: J.P. Christodouleas: None. B.C. Baumann: None. W.R. Bosch: None. A. Bahl: None. A. Birtle: None. R. Breau: None. A. Challapalli: None. A.J. Chang: None. A. Choudhury: None. S. Daneshmand: None. A.S. Feldman: None. T. Guzzo: None. S. Hilman: None. A. Jani: None. B. Malkowicz: None. V.A. Master: None. A. Mitra: None. S. Porten: None. J.A. Efstathiou: None. L. Eapen: None.
54 Factors Associated With Regional Recurrence Following Lymphadenectomy for Penile Squamous Cell Carcinoma: One Institutions Experience J. Reddy,1 L.B. Levy,2 C.A. Pettaway,1 L. Pagliaro,1 P. Tamboli,1 P. Rao,1 I. Jayaratna,1 and K.E. Hoffman1; 1MD Anderson Cancer Center, Houston, TX, 2The University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Factors associated with regional recurrence (RR) following lymphadenectomy for penile cancer were assessed to determine which patients might benefit from adjuvant therapy. Materials/Methods: Men who underwent lymphadenectomy for penile squamous cell carcinoma from 1978 to 2014 were identified from an institutional database. Kaplan-Meier curves estimated time to RR calculated from the date of lymphadenectomy. Cox proportional hazards models evaluated the association between RR and patient and tumor characteristics. Backward selection with P-value cutoff of .05 selected covariates into the multivariate model. Results: A total of 173 men underwent lymphadenectomy and did not receive adjuvant radiation therapy. Of these patients, 50.3% underwent inguinal lymphadenectomy, and 49.1% underwent inguinal and pelvic lymphadenectomy. A further 26% of patients received neoadjuvant chemotherapy, and 8.1% received adjuvant chemotherapy. Median patient age was 63 years (range, 23e93), and median follow-up for living patients was 4.1 years. Of 29 men who experienced RR following lymphadenectomy, 21 of them developed isolated RR. Among men who failed, median time to RR was 4.9 months (IQR, 3.8e10.8). Three and 5-year cumulative incidence of RR were 17.7% and 18.7%, respectively. On univariate analysis, clinical N3 disease (P < .001), the presence of extranodal extension at lymphadenectomy (ENE, P < .001), and involvement of >3 nodes at lymphadenectomy (P < .001) were associated with RR. Threeyear RR was 42.7% in men with ENE and 8.6% in men without ENE. For men with >3 involved nodes, 3-year RR was 58.5% versus 9.8% in men with <3 involved nodes. Three-year RR for men with cN0, cN1, cN2, and cN3 disease was 5.6%, 21.2%, 17.6%, and 41.4%, respectively. On multivariate analysis, >3 pathologically involved nodes (AHR Z 8.53,
S25
95% CI: 3.5e20.69; P < .0001), ENE (AHR Z 7.30, 95% CI: 3.00e17.77; P < .001), and lack of adjuvant chemotherapy (AHR Z 8.08, 95% CI: 1.71e38.07; P Z .008) were associated with RR. Median survival for men who experienced RR was 11.3 months compared to 15.3 years for men who did not develop RR. Conclusion: The presence >3 lymph nodes after lymphadenectomy, ENE, and lack of adjuvant chemotherapy were associated with increased risk of RR. Since RR portends a dismal prognosis with few salvage options, men with these adverse factors should be considered for adjuvant therapy, including radiation therapy, to reduce RR. Author Disclosure: J. Reddy: None. L.B. Levy: None. C.A. Pettaway: None. L. Pagliaro: None. P. Tamboli: None. P. Rao: None. I. Jayaratna: None. K.E. Hoffman: Research Grant; ASTRO. Consultant; Vanderbilt University. Science Workshops Subcommittee; ASTRO. Best Practices Subcommittee; ASTRO.
55 Patterns of Care and Propensity Score–Adjusted Survival in Stage I Testicular Seminoma S.M. Glaser,1 J. Vargo,1 G. Balasubramani,2 and S. Beriwal1; 1University of Pittsburgh Cancer Institute, Pittsburgh, PA, 2University of Pittsburgh School of Public Health, Pittsburgh, PA Purpose/Objective(s): The majority of stage I seminoma patients are cured by orchiectomy alone, leading many to advocate for active surveillance (AS) over adjuvant treatment (AT). This concept has not been tested in a prospective, randomized trial. AT can be either radiation therapy (RT) or chemotherapy (CT). We sought to analyze the factors affecting adjuvant treatment decisions and resulting survival outcomes using a population-based cohort. Materials/Methods: We identified 33,094 stage I seminoma patients following orchiectomy from 1998 to 2012 from the National Cancer Database. Factors affecting treatment selection (AS vs. AT) were studied using a parsimonious multivariate logistic regression model. Propensity scores for treatment decision were generated and incorporated into a multivariate Cox regression analysis of overall survival. This process was then repeated within the AT cohort for factors predictive for CT versus RT. Results: Only 33% received AS and 65% received AT (89% RT and 11% CT). From 1998 to 2012, the proportion receiving AS increased from 23% to 60%, while RT utilization decreased from 73% to 21%, and CT utilization increased from 2% to 17%. Factors associated with AS utilization over ATon multivariate analysis included later year of diagnosis, lower T stage, smaller tumors, negative surgical margins, pathologic examination of lymph nodes, lower facility volume, treatment at an academic center, increasing distance from facility, being uninsured, and geographic location. Factors associated with RT utilization over CT on multivariate analysis included earlier year of diagnosis, non-Hispanic ethnicity, private insurance, nonacademic center, lower T stage, closer distance to facility, no pathologic lymph node examination, and geographic location. At a median follow-up of 67 months (IQR Z 36e108 mo), the 10-yr overall survival (OS) was higher for AT than AS at 95.0% (95% CI Z 94.6e95.4) versus 93.4% (95% CI Z 92.6e94.2) with a propensity score adjusted hazard ratio (HR) of 0.61 (95% CI Z 0.48e.76, P < .0001). This remained significant with a 6-month conditional landmark analysis (HR Z 0.62, 95% CI Z 0.49e0.78). Increased OS with treatment persisted across subset analysis including T stage, age, LVSI, and tumor size. The 10-yr OS was similar between CT and RT at 92.5% (95% CI Z 89.5e95.5) versus 95.1% (95% CI Z 94.7e95.5) with a propensity score adjusted HR of 0.97 (95% CI Z 0.59e1.61, P Z .91). Conclusion: Consistent with National Comprehensive Cancer Network guidelines, there has been a significant increase in use of AS for stage I seminoma, influenced by both sociodemographic and clinicopathologic factors. Between AT options, there has been a significant increase in use of CT mirrored by a decline in the use of RT. While overall survival remains high for all three treatment strategies, AT appears to be associated with a small absolute survival advantage over AS. Author Disclosure: S.M. Glaser: None. J. Vargo: None. G. Balasubramani: None. S. Beriwal: None.