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Predictors of Rapid Treatment Failure After Postoperative Radiation Therapy: A Multicenter Study
S184
International Journal of Radiation Oncology Biology Physics
Purpose/Objective(s): To examine the role of local treatment, in the form of radiation therapy (RT) or radical prostatectomy (RP), and its association on outcomes in patients who present with metastatic prostate cancer. Materials/Methods: Using the National Cancer Database (NCDB), we evaluated clinical features and survival outcomes among patients diagnosed with metastatic prostate cancer from 2004 to 2013. The association between local therapy (RP, intensity-modulated radiation therapy [IMRT], 2D/3D-conformal radiation therapy [CRT]), co-variables, and outcomes was assessed in a multivariate Cox proportional hazards regression model. Propensity score (PS) matching was performed to balance observed confounding factors. Survival was estimated using the Kaplan-Meier method. Results: Among the 1,208,180 patients in the NCDB with prostate cancer, 6,051 patients with metastatic disease at the time of diagnosis, met the inclusion criteria (adenocarcinoma histology, M1+ disease, no chemotherapy, no brachytherapy, treated within 1 year of diagnosis) for analysis. Median age was 72 years old, and median follow-up was 22 months. No local therapy was used in 5,224 patients, while 622 (10.3%), 52 (0.9%), 153 (2.5%) patients received RP, IMRT, and 2D/3D-CRT, respectively. Treatment with local therapy was associated with younger age (70 years), lower co-morbidity score, Gleason score <8, lower T stage, node-negative status, private and Medicare insurance, higher income quartile, and treatment at comprehensive cancer programs and academic/research centers (P < 0.05). Five-year overall survival for patients receiving local therapy (RP or IMRT) was 45.7% versus 17.1% for those not receiving local therapy (P < 0.01). In multivariate analysis, RP (HR Z 0.51, 95% CI Z 0.45e0.59, P < 0.01) and IMRT (HR Z 0.47, 95% CI Z 0.31e0.72, P < 0.01) were independently associated with an improvement in overall survival. After PS-matching based on clinicopathologic characteristics, the use of local therapy (RP or IMRT) remained significantly associated with overall survival (HR Z 0.35, 95% CI Z 0.30e0.41, P < 0.01). Conclusion: The use of RP and IMRT, to treat the primary disease, was associated with an improvement in overall survival for patients with metastatic prostate cancer. We have identified patient-specific variations in the use of local therapy that may be tested in subsequent prospective clinical trials to improve patient outcomes in this setting. Author Disclosure: J. Byun: None. S. Goyal: None. I.Y. Kim: None. R.R. Parikh: None.
Results: Between December 2003 and December 2014, the total number of enrolled patients in all three institutions was 2157 (institution A: n Z 1432, institution B: n Z 515, institution C: n Z 210). The number of patients in low-risk, intermediate-risk, and high-risk groups were 263, 679, and 1215, respectively. A total of 1895 patients (81%) underwent androgen deprivation therapy. The median follow-up periods of surviving patients in the institution A, institution B, and institution C were 43, 23, and 7 months (range 0.5-133.7 months), respectively. The five-year biochemical relapsefree survivals (bRFS) in low-risk, intermediate-risk, and high-risk patients were 92%, 89%, and 92%, respectively. The ten-year bRFS in low-risk, intermediate-risk, and high-risk patients were 77%, 70%, and 79%, respectively. The five-year local control rates (LCR) and cause-specific survivals (CSS) in low-risk, intermediate-risk, and high-risk patients were 98%, 96%, and 99% for LCR, respectively, and 100%, 100%, and 99% for CSS, respectively. The incidence of grade (G) 2 and G3 late toxicities were 4.2% and 0% for the bladder, and 0.5% and 0% for the rectum, respectively. Conclusion: Analysis of the first multi-institutional data on CIRT for prostate cancer suggested that the overall outcomes of CIRT were favorable, especially in high-risk patients. In addition, no severe acute/late toxicities were observed in long-term follow-up. Author Disclosure: T. Nomiya: None. H. Tsuji: None. H. Kawamura: None. T. Ohno: None. S. Toyama: None. Y. Shioyama: None. Y. Nakayama: None. K. Nemoto: None. H. Tsujii: None. T. Kamada: None.
1047 A Multi-institutional Analysis of Prospective Studies of Carbon Ion Radiation Therapy for Prostate Cancer: An Analysis of 2157 Patients from the Japan Carbon Ion Radiation Oncology Study Group (J-CROS) T. Nomiya,1 H. Tsuji,2 H. Kawamura,3 T. Ohno,4 S. Toyama,5 Y. Shioyama,5 Y. Nakayama,6 K. Nemoto,7 H. Tsujii,8 and T. Kamada2; 1 Kanagawa Cancer Center, Yokohama, Japan, 2Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan, 3Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan, 4Gunma University Heavy Ion Medical Center, Maebashi, Japan, 5Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu, Japan, 6Department of Radiation Oncology, Kanagawa Cancer Center, Yokohama 241-0815, Japan, 7Department of Radiation Oncology, Yamagata University Faculty of Medicine, Yamagata, Japan, 8National Institute of Radiological Sciences, Chiba, Japan Purpose/Objective(s): The number of carbon ion radiation therapy (CIRT) institutions has been increasing in Japan. This is the first multi-institutional analysis of the outcomes of CIRT in patients with prostate cancer. Materials/Methods: Data of patients enrolled in prospective clinical trials performed at 3 CIRT institutions were retrospectively analyzed. All patient risks were reclassified according to the D’Amico risk classification. A short-term hormonal therapy (6 months) and a long-term hormonal therapy (24 months) were combined with CIRT for the intermediate-risk group and the high-risk group, respectively. Hormonal therapy was not combined in low-risk group. The biochemical failure was defined as a rise of >2.0 ng/mL above PSA nadir (Phoenix definition).
1048 Predictors of Rapid Treatment Failure After Postoperative Radiation Therapy: A Multicenter Study W.C. Jackson,1 N.B. Desai,2 V. Tumati,3 J.Y. Lee,1 R.T. Dess,1 P.D. Soni,1 A. Abugharib,4 D.A. Hamstra,5 J.W.D. Hearn,1 H.M. Sandler,6 Z.S. Zumsteg,6 J. Montgomery,1 B. Hollenbeck,1 D. Miller,1 G. Palapattu,1 S.A. Tomlins,1 R. Mera,1 T. Morgan,1 F.Y. Feng,1 and D.E. Spratt1; 1University of Michigan, Ann Arbor, MI, 2University of Texas Southwestern Medical Center, Dallas, TX, 3 University of Texas Southwestern Medical Center, Dallas, TX, United States, 4 Department of Oncology, Sohag University, Sohag, Egypt, 5Texas Oncology, Irving, TX, 6Cedars-Sinai Medical Center, Los Angeles, CA Purpose/Objective(s): Post-radical prostatectomy (RP) radiation therapy (RT) for prostate cancer is delivered with the assumption that residual disease remains localized within the post-operative bed. However, only 3070% of patients remain disease-free long term, suggesting the presence of either micrometastatic or radioresistant disease. To identify these patients, we analyzed predictors of rapid early PSA progression within the first year following post-RP RT. Materials/Methods: A retrospective multi-institutional study was performed on 608 consecutive men who underwent a RP and pelvic lymph node (LN) dissection and received post-operative RT (adjuvant or salvage) between 1986 and 2013. LN positive patients were excluded. The median RT dose was 66.6 Gy, and 141 men received androgen deprivation therapy (ADT) in addition to RT. Biochemical recurrence (BCR) was defined as a rise in PSA of 0.2 ng/mL or greater above the PSA nadir followed by a sequentially equal or higher PSAvalue. Rapid early BCR was defined as BCR within the first year post-RT. Kaplan-Meier methods were used to assess rates of BCR. Predictors of rapid early progression were assessed using univariable and multivariable Cox proportional hazard methods. Results: A total of 119 men (20%) experienced BCR within one year of completing RT. 41 men (7%) had a continuously rising PSA despite receiving post-RP RT. Men who experienced a rapid early BCR had significantly higher pre-RT PSAs (median, 0.7 vs 0.3 ng/mL, P Z 0.02), were more likely to have Gleason 9-10 disease (26% vs. 13%, P Z 0.02), and pathologic T3b-T4 disease (30% vs. 20%, P Z 0.048) compared to men who did not experience a rapid early BCR. On univariate analysis, the use of pelvic LN irradiation had no impact on rapid early BCR. However, positive surgical margin [SM] (HR Z 0.6, P Z 0.002) and use of ADT (HR Z 0.6, P Z 0.03) were associated with decreased risk of rapid early BCR. On multivariate analysis, Gleason score (HR Z 1.4, P Z 0.004), pre-RT PSA (HR Z 1.2, P Z 0.004), and pT-stage (HR Z 1.2, P Z 0.03) were all associated with a rapid early BCR, whereas a positive SM (HR Z 0.5,
Volume 96 Number 2S Supplement 2016 P Z 0.001), and ADT use (HR Z 0.5, P Z 0.04) were again protective. For men with a pre-RT PSA >0.7 ng/mL, 1-year rates of BCR were 32% compared to 16% for men with a pre-RT PSA <0.7 ng/mL (P < 0.0001). Conclusion: BCR within one year of completing post-operative RT is a relatively common occurrence. This phenomenon suggests that these patients harbor either micrometastatic or radioresistant disease at time of RT. Given recent evidence that ADT inhibits DNA repair, in addition to ADT’s effect on micrometastatic disease, we would recommend the use of postoperative RT in combination with ADT in patients with a pre-RT PSA >0.7 ng/mL, consistent with the recently presented RTOG 9601 subgroup analysis. Overall, improved biomarkers are needed to predict the likelihood of micro-metastatic disease in order to avoid potentially futile local therapies in these men. Author Disclosure: W.C. Jackson: None. N.B. Desai: None. V. Tumati: None. J.Y. Lee: None. R.T. Dess: None. P.D. Soni: None. A. Abugharib: None. D.A. Hamstra: Consultant; Medivation. J.W. Hearn: None. H.M. Sandler: None. Z.S. Zumsteg: None. J. Montgomery: None. B. Hollenbeck: None. D. Miller: None. G. Palapattu: None. S.A. Tomlins: Research Grant; Alfred Taubman Medical Research Institute. Advisor; Medivation/Astellas, Jansse. R. Mera: Research Grant; Prostate cancer foundation. T. Morgan: Research Grant; PCF and Alfred Taubman Medical Research Institute, MDxHealth, Myriad Genetics. Advisor; MDxHealth, Myriad Genetics. F.Y. Feng: Research Grant; Varian, Medivation/Astellas, Celgen. Advisor; Medivation/Astellas, GenomeDx, Nanostring, Celgene. D.E. Spratt: Research Grant; PCF.
1049 Second Malignancies as First Cause of Death in Localized Prostate Cancer Treated With Radiation Therapy: Data from Two Phase 3 Trials A. Nabid,1 N. Carrier,1 E. Vigneault,2 L. Souhami,3 C. Lemaire,4 M.A. Brassard,5 B. Bahoric,6 R. Archambault,7 F. Vincent,8 and T.V. Nguyen9; 1CHUS, Sherbrooke, QC, Canada, 2Centre Hospitalier Universitaire de Que´bec, Que´bec, QC, Canada, 3McGill University Health Centre, Montreal, QC, Canada, 4Maisonneuve-Rosemont Hospital, Montreal, QC, Canada, 5CSSS de Chicoutimi, Chicoutimi, QC, Canada, 6 Jewish General Hospital, McGill University, Montreal, QC, Canada, 7 CSSSG, Gatineau, QC, Canada, 8Hopital Universitaire de Trois Rivieres, Trois Rivieres, QC, Canada, 9Centre Hospitalier Universitaire de Montre´al, Montre´al, QC, Canada Purpose/Objective(s): The purpose of this analysis was to establish the rate of death due to second malignancies (SM) in a cohort of localized prostate patients treated with radiation therapy (RT) in two prospective trials. Materials/Methods: From October 2000 to September 2010, 1230 patients were randomized: 630 with high risk prostate cancer (HRPC) treated with androgen deprivation therapy (ADT) and RT (PCS IV ClinicalTrials.gov #NCT00223171) and 600 with intermediate risk prostate cancer (IRPC) treated with RT with or without ADT (PCS III ClinicalTrials.gov #NCT00223145). SM and Causes of death were established from data sent by the different investigators and centrally reviewed. They were based on clinical records, family members’ information, death certificates, and family physician records. All data were compiled until January 2016. Results: With a median follow up of 8 years (HRPC 8.4 vs IRPC 7.4, P < 0.001), 15.8% of patients (194/1230) developed SM (HRPC 16.7% vs IRPC 14.8%, P Z 0.378). SM occurred at a median age of 76.8 years (interquartile range [IQR], 72.7-80.3). From randomization, the median time to develop a SM was 5.28 years (IQR: 3.02e7.62) and was similar for both groups. 31.3% of patients (385/1230) had died (HRPC 38.6% vs IRPC 23.7%, P < 0.001). The most frequent cause of death was a SM (122/1230, 9.9%, HRPC 11.0% vs IRPC 8.8%, P Z 0.214), cardiovascular deaths occurred in 6.6% of patients (81/1230) (HRPC 7.3% vs IRPC 5.8%, P Z 0.299) while 4.6% (57/1230) died from prostate cancer (HRPC 7.6% vs IRPC 1.5%, P < 0.001). For the 122/194 (62.9%) patients who developed SM and died of it, rate of deaths by sites were: respiratory 48/64 (75%), gastrointestinal (GI) 32/52 (61.5%), genitourinary (GU) 12/28 (42.9%), hematology 16/24 (66.7%), dermatology (melanoma) 2/10 (20%), and others 13/16. Patients treated with a larger field of RT (pelvic +
ePoster Sessions S185 prostate RT in HRPC vs prostate RT in IRPC) had a higher incidence of GI and GU SM (rectum, bladder, penis, testis) but the difference was not significant (HRPC 3.2% vs IRPC 1.7%, P Z 0.087). In a multivariate Cox regression analysis over the entire period of follow up time, the occurrence of SM was highly significant to predict time to death, (hazard ratio [HR] Z 3.22, 95% CI Z 2.61-3.97, P < 0.001), followed by age in years (HR Z 1.05, 95% CI Z 1.03-1.07, P < 0.001), than by HRPC vs IRPC (HR Z 1.37, 95% CI Z 1.11-1.69, P Z 0.003). Biochemical failure had no significant impact on survival (HR Z 1.00, 95% CI Z 0.80-1.27, P Z 0.970). Conclusion: In localized prostate cancer patients treated with radiotherapy, one over ten patients will die from a second malignancy, the leading cause of deaths. Considering this major impact on prostate cancer survivorship, appropriate surveillance, prevention, and education strategies are urgently needed to be developed. Acknowledgments: AstraZeneca Pharmaceuticals Grant Author Disclosure: A. Nabid: Advisory Board; Bayer, Janssen, Sanofi, Astellas. Travel Expenses; Sanofi. N. Carrier: None. E. Vigneault: None. L. Souhami: None. C. Lemaire: None. M. Brassard: None. B. Bahoric: None. R. Archambault: None. F. Vincent: None. T. Nguyen: None.
1050 Androgen Deprivation Therapy and Risk of Dementia K.T. Nead,1 G. Gaskin,2 C. Chester,2 S.D. Swisher-McClure,1 N.J. Leeper,2 and N.H. Shah2; 1University of Pennsylvania, Philadelphia, PA, 2Stanford University, Stanford, CA Purpose/Objective(s): Androgen deprivation therapy (ADT) is a mainstay of treatment for prostate cancer. While most individuals return to normal testosterone levels following treatment, 20% to 30% have prolonged androgen suppression. Concerningly, androgens have been shown to aid in neuron growth and axonal regeneration with multiple studies showing an association between ADT and cognitive dysfunction. In the current analysis we utilize an informatics approach using electronic medical record data from more than 1.2 million patients to examine the association of ADT with the subsequent development of dementia among men with prostate cancer. Materials/Methods: We used a previously validated and implemented text-processing pipeline to analyze electronic medical record data in a retrospective cohort of patients. We extracted International Classification of Diseases-9th (ICD-9) revision diagnosis and Current Procedural Terminology codes, medication lists, and positive-present mentions of drug and disease concepts from all clinical notes. New-onset dementia was defined using terms from clinical notes and ICD-9 diagnostic codes 290.0290.9, 331.0-331.2, and 294.1-294.21. We then tested the effect of ADT on risk of dementia using 1:5 propensity scoreematched and traditional Cox proportional hazards models. Traditional models were adjusted for age at prostate cancer diagnosis, race, smoking status, use of antiplatelet, anticoagulant, antihypertensive, and statin medications, and a history of cardiovascular disease, diabetes, or malignancy. We also tested whether the duration of ADT use was association with dementia risk. Results: There were 9,501 men with prostate cancer meeting all study criteria with 1,921 (20.2%) receiving ADT. During a median follow-up period of 4.6 years (interquartile range, 0.9-7.1 years) 297 patients were diagnosed with dementia. Propensity scoreematched analysis (hazard ratio, 1.64; 95% CI Z 1.20 to 2.23; P Z 0.002) and traditional multivariable Cox regression analysis (hazard ratio, 1.81; 95% CI Z 1.39 to 2.37; P < 0.001) both supported a statistically significant association between ADT use and dementia risk. We also observed a statistically significant increased risk of dementia with increasing duration of ADT (P for trend < 0.001) with individuals undergoing ADT for greater than 1 year having the highest risk (hazard ratio, 1.96; 95% CI Z 1.38 to 2.78; P < 0.001) in propensity scoreematched models. Conclusion: Our results support an association between the use of ADT in the treatment of prostate cancer and an increased risk of dementia in a general population cohort. Future prospective studies are needed to confirm this finding. Author Disclosure: K.T. Nead: None. G. Gaskin: None. C. Chester: None. S.D. Swisher-McClure: None. N.J. Leeper: None. N.H. Shah: Stock; Kyron, Apixio.
International Journal of Radiation Oncology Biology Physics
Purpose/Objective(s): To examine the role of local treatment, in the form of radiation therapy (RT) or radical prostatectomy (RP), and its association on outcomes in patients who present with metastatic prostate cancer. Materials/Methods: Using the National Cancer Database (NCDB), we evaluated clinical features and survival outcomes among patients diagnosed with metastatic prostate cancer from 2004 to 2013. The association between local therapy (RP, intensity-modulated radiation therapy [IMRT], 2D/3D-conformal radiation therapy [CRT]), co-variables, and outcomes was assessed in a multivariate Cox proportional hazards regression model. Propensity score (PS) matching was performed to balance observed confounding factors. Survival was estimated using the Kaplan-Meier method. Results: Among the 1,208,180 patients in the NCDB with prostate cancer, 6,051 patients with metastatic disease at the time of diagnosis, met the inclusion criteria (adenocarcinoma histology, M1+ disease, no chemotherapy, no brachytherapy, treated within 1 year of diagnosis) for analysis. Median age was 72 years old, and median follow-up was 22 months. No local therapy was used in 5,224 patients, while 622 (10.3%), 52 (0.9%), 153 (2.5%) patients received RP, IMRT, and 2D/3D-CRT, respectively. Treatment with local therapy was associated with younger age (70 years), lower co-morbidity score, Gleason score <8, lower T stage, node-negative status, private and Medicare insurance, higher income quartile, and treatment at comprehensive cancer programs and academic/research centers (P < 0.05). Five-year overall survival for patients receiving local therapy (RP or IMRT) was 45.7% versus 17.1% for those not receiving local therapy (P < 0.01). In multivariate analysis, RP (HR Z 0.51, 95% CI Z 0.45e0.59, P < 0.01) and IMRT (HR Z 0.47, 95% CI Z 0.31e0.72, P < 0.01) were independently associated with an improvement in overall survival. After PS-matching based on clinicopathologic characteristics, the use of local therapy (RP or IMRT) remained significantly associated with overall survival (HR Z 0.35, 95% CI Z 0.30e0.41, P < 0.01). Conclusion: The use of RP and IMRT, to treat the primary disease, was associated with an improvement in overall survival for patients with metastatic prostate cancer. We have identified patient-specific variations in the use of local therapy that may be tested in subsequent prospective clinical trials to improve patient outcomes in this setting. Author Disclosure: J. Byun: None. S. Goyal: None. I.Y. Kim: None. R.R. Parikh: None.
Results: Between December 2003 and December 2014, the total number of enrolled patients in all three institutions was 2157 (institution A: n Z 1432, institution B: n Z 515, institution C: n Z 210). The number of patients in low-risk, intermediate-risk, and high-risk groups were 263, 679, and 1215, respectively. A total of 1895 patients (81%) underwent androgen deprivation therapy. The median follow-up periods of surviving patients in the institution A, institution B, and institution C were 43, 23, and 7 months (range 0.5-133.7 months), respectively. The five-year biochemical relapsefree survivals (bRFS) in low-risk, intermediate-risk, and high-risk patients were 92%, 89%, and 92%, respectively. The ten-year bRFS in low-risk, intermediate-risk, and high-risk patients were 77%, 70%, and 79%, respectively. The five-year local control rates (LCR) and cause-specific survivals (CSS) in low-risk, intermediate-risk, and high-risk patients were 98%, 96%, and 99% for LCR, respectively, and 100%, 100%, and 99% for CSS, respectively. The incidence of grade (G) 2 and G3 late toxicities were 4.2% and 0% for the bladder, and 0.5% and 0% for the rectum, respectively. Conclusion: Analysis of the first multi-institutional data on CIRT for prostate cancer suggested that the overall outcomes of CIRT were favorable, especially in high-risk patients. In addition, no severe acute/late toxicities were observed in long-term follow-up. Author Disclosure: T. Nomiya: None. H. Tsuji: None. H. Kawamura: None. T. Ohno: None. S. Toyama: None. Y. Shioyama: None. Y. Nakayama: None. K. Nemoto: None. H. Tsujii: None. T. Kamada: None.
1047 A Multi-institutional Analysis of Prospective Studies of Carbon Ion Radiation Therapy for Prostate Cancer: An Analysis of 2157 Patients from the Japan Carbon Ion Radiation Oncology Study Group (J-CROS) T. Nomiya,1 H. Tsuji,2 H. Kawamura,3 T. Ohno,4 S. Toyama,5 Y. Shioyama,5 Y. Nakayama,6 K. Nemoto,7 H. Tsujii,8 and T. Kamada2; 1 Kanagawa Cancer Center, Yokohama, Japan, 2Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan, 3Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan, 4Gunma University Heavy Ion Medical Center, Maebashi, Japan, 5Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu, Japan, 6Department of Radiation Oncology, Kanagawa Cancer Center, Yokohama 241-0815, Japan, 7Department of Radiation Oncology, Yamagata University Faculty of Medicine, Yamagata, Japan, 8National Institute of Radiological Sciences, Chiba, Japan Purpose/Objective(s): The number of carbon ion radiation therapy (CIRT) institutions has been increasing in Japan. This is the first multi-institutional analysis of the outcomes of CIRT in patients with prostate cancer. Materials/Methods: Data of patients enrolled in prospective clinical trials performed at 3 CIRT institutions were retrospectively analyzed. All patient risks were reclassified according to the D’Amico risk classification. A short-term hormonal therapy (6 months) and a long-term hormonal therapy (24 months) were combined with CIRT for the intermediate-risk group and the high-risk group, respectively. Hormonal therapy was not combined in low-risk group. The biochemical failure was defined as a rise of >2.0 ng/mL above PSA nadir (Phoenix definition).
1048 Predictors of Rapid Treatment Failure After Postoperative Radiation Therapy: A Multicenter Study W.C. Jackson,1 N.B. Desai,2 V. Tumati,3 J.Y. Lee,1 R.T. Dess,1 P.D. Soni,1 A. Abugharib,4 D.A. Hamstra,5 J.W.D. Hearn,1 H.M. Sandler,6 Z.S. Zumsteg,6 J. Montgomery,1 B. Hollenbeck,1 D. Miller,1 G. Palapattu,1 S.A. Tomlins,1 R. Mera,1 T. Morgan,1 F.Y. Feng,1 and D.E. Spratt1; 1University of Michigan, Ann Arbor, MI, 2University of Texas Southwestern Medical Center, Dallas, TX, 3 University of Texas Southwestern Medical Center, Dallas, TX, United States, 4 Department of Oncology, Sohag University, Sohag, Egypt, 5Texas Oncology, Irving, TX, 6Cedars-Sinai Medical Center, Los Angeles, CA Purpose/Objective(s): Post-radical prostatectomy (RP) radiation therapy (RT) for prostate cancer is delivered with the assumption that residual disease remains localized within the post-operative bed. However, only 3070% of patients remain disease-free long term, suggesting the presence of either micrometastatic or radioresistant disease. To identify these patients, we analyzed predictors of rapid early PSA progression within the first year following post-RP RT. Materials/Methods: A retrospective multi-institutional study was performed on 608 consecutive men who underwent a RP and pelvic lymph node (LN) dissection and received post-operative RT (adjuvant or salvage) between 1986 and 2013. LN positive patients were excluded. The median RT dose was 66.6 Gy, and 141 men received androgen deprivation therapy (ADT) in addition to RT. Biochemical recurrence (BCR) was defined as a rise in PSA of 0.2 ng/mL or greater above the PSA nadir followed by a sequentially equal or higher PSAvalue. Rapid early BCR was defined as BCR within the first year post-RT. Kaplan-Meier methods were used to assess rates of BCR. Predictors of rapid early progression were assessed using univariable and multivariable Cox proportional hazard methods. Results: A total of 119 men (20%) experienced BCR within one year of completing RT. 41 men (7%) had a continuously rising PSA despite receiving post-RP RT. Men who experienced a rapid early BCR had significantly higher pre-RT PSAs (median, 0.7 vs 0.3 ng/mL, P Z 0.02), were more likely to have Gleason 9-10 disease (26% vs. 13%, P Z 0.02), and pathologic T3b-T4 disease (30% vs. 20%, P Z 0.048) compared to men who did not experience a rapid early BCR. On univariate analysis, the use of pelvic LN irradiation had no impact on rapid early BCR. However, positive surgical margin [SM] (HR Z 0.6, P Z 0.002) and use of ADT (HR Z 0.6, P Z 0.03) were associated with decreased risk of rapid early BCR. On multivariate analysis, Gleason score (HR Z 1.4, P Z 0.004), pre-RT PSA (HR Z 1.2, P Z 0.004), and pT-stage (HR Z 1.2, P Z 0.03) were all associated with a rapid early BCR, whereas a positive SM (HR Z 0.5,
Volume 96 Number 2S Supplement 2016 P Z 0.001), and ADT use (HR Z 0.5, P Z 0.04) were again protective. For men with a pre-RT PSA >0.7 ng/mL, 1-year rates of BCR were 32% compared to 16% for men with a pre-RT PSA <0.7 ng/mL (P < 0.0001). Conclusion: BCR within one year of completing post-operative RT is a relatively common occurrence. This phenomenon suggests that these patients harbor either micrometastatic or radioresistant disease at time of RT. Given recent evidence that ADT inhibits DNA repair, in addition to ADT’s effect on micrometastatic disease, we would recommend the use of postoperative RT in combination with ADT in patients with a pre-RT PSA >0.7 ng/mL, consistent with the recently presented RTOG 9601 subgroup analysis. Overall, improved biomarkers are needed to predict the likelihood of micro-metastatic disease in order to avoid potentially futile local therapies in these men. Author Disclosure: W.C. Jackson: None. N.B. Desai: None. V. Tumati: None. J.Y. Lee: None. R.T. Dess: None. P.D. Soni: None. A. Abugharib: None. D.A. Hamstra: Consultant; Medivation. J.W. Hearn: None. H.M. Sandler: None. Z.S. Zumsteg: None. J. Montgomery: None. B. Hollenbeck: None. D. Miller: None. G. Palapattu: None. S.A. Tomlins: Research Grant; Alfred Taubman Medical Research Institute. Advisor; Medivation/Astellas, Jansse. R. Mera: Research Grant; Prostate cancer foundation. T. Morgan: Research Grant; PCF and Alfred Taubman Medical Research Institute, MDxHealth, Myriad Genetics. Advisor; MDxHealth, Myriad Genetics. F.Y. Feng: Research Grant; Varian, Medivation/Astellas, Celgen. Advisor; Medivation/Astellas, GenomeDx, Nanostring, Celgene. D.E. Spratt: Research Grant; PCF.
1049 Second Malignancies as First Cause of Death in Localized Prostate Cancer Treated With Radiation Therapy: Data from Two Phase 3 Trials A. Nabid,1 N. Carrier,1 E. Vigneault,2 L. Souhami,3 C. Lemaire,4 M.A. Brassard,5 B. Bahoric,6 R. Archambault,7 F. Vincent,8 and T.V. Nguyen9; 1CHUS, Sherbrooke, QC, Canada, 2Centre Hospitalier Universitaire de Que´bec, Que´bec, QC, Canada, 3McGill University Health Centre, Montreal, QC, Canada, 4Maisonneuve-Rosemont Hospital, Montreal, QC, Canada, 5CSSS de Chicoutimi, Chicoutimi, QC, Canada, 6 Jewish General Hospital, McGill University, Montreal, QC, Canada, 7 CSSSG, Gatineau, QC, Canada, 8Hopital Universitaire de Trois Rivieres, Trois Rivieres, QC, Canada, 9Centre Hospitalier Universitaire de Montre´al, Montre´al, QC, Canada Purpose/Objective(s): The purpose of this analysis was to establish the rate of death due to second malignancies (SM) in a cohort of localized prostate patients treated with radiation therapy (RT) in two prospective trials. Materials/Methods: From October 2000 to September 2010, 1230 patients were randomized: 630 with high risk prostate cancer (HRPC) treated with androgen deprivation therapy (ADT) and RT (PCS IV ClinicalTrials.gov #NCT00223171) and 600 with intermediate risk prostate cancer (IRPC) treated with RT with or without ADT (PCS III ClinicalTrials.gov #NCT00223145). SM and Causes of death were established from data sent by the different investigators and centrally reviewed. They were based on clinical records, family members’ information, death certificates, and family physician records. All data were compiled until January 2016. Results: With a median follow up of 8 years (HRPC 8.4 vs IRPC 7.4, P < 0.001), 15.8% of patients (194/1230) developed SM (HRPC 16.7% vs IRPC 14.8%, P Z 0.378). SM occurred at a median age of 76.8 years (interquartile range [IQR], 72.7-80.3). From randomization, the median time to develop a SM was 5.28 years (IQR: 3.02e7.62) and was similar for both groups. 31.3% of patients (385/1230) had died (HRPC 38.6% vs IRPC 23.7%, P < 0.001). The most frequent cause of death was a SM (122/1230, 9.9%, HRPC 11.0% vs IRPC 8.8%, P Z 0.214), cardiovascular deaths occurred in 6.6% of patients (81/1230) (HRPC 7.3% vs IRPC 5.8%, P Z 0.299) while 4.6% (57/1230) died from prostate cancer (HRPC 7.6% vs IRPC 1.5%, P < 0.001). For the 122/194 (62.9%) patients who developed SM and died of it, rate of deaths by sites were: respiratory 48/64 (75%), gastrointestinal (GI) 32/52 (61.5%), genitourinary (GU) 12/28 (42.9%), hematology 16/24 (66.7%), dermatology (melanoma) 2/10 (20%), and others 13/16. Patients treated with a larger field of RT (pelvic +
ePoster Sessions S185 prostate RT in HRPC vs prostate RT in IRPC) had a higher incidence of GI and GU SM (rectum, bladder, penis, testis) but the difference was not significant (HRPC 3.2% vs IRPC 1.7%, P Z 0.087). In a multivariate Cox regression analysis over the entire period of follow up time, the occurrence of SM was highly significant to predict time to death, (hazard ratio [HR] Z 3.22, 95% CI Z 2.61-3.97, P < 0.001), followed by age in years (HR Z 1.05, 95% CI Z 1.03-1.07, P < 0.001), than by HRPC vs IRPC (HR Z 1.37, 95% CI Z 1.11-1.69, P Z 0.003). Biochemical failure had no significant impact on survival (HR Z 1.00, 95% CI Z 0.80-1.27, P Z 0.970). Conclusion: In localized prostate cancer patients treated with radiotherapy, one over ten patients will die from a second malignancy, the leading cause of deaths. Considering this major impact on prostate cancer survivorship, appropriate surveillance, prevention, and education strategies are urgently needed to be developed. Acknowledgments: AstraZeneca Pharmaceuticals Grant Author Disclosure: A. Nabid: Advisory Board; Bayer, Janssen, Sanofi, Astellas. Travel Expenses; Sanofi. N. Carrier: None. E. Vigneault: None. L. Souhami: None. C. Lemaire: None. M. Brassard: None. B. Bahoric: None. R. Archambault: None. F. Vincent: None. T. Nguyen: None.
1050 Androgen Deprivation Therapy and Risk of Dementia K.T. Nead,1 G. Gaskin,2 C. Chester,2 S.D. Swisher-McClure,1 N.J. Leeper,2 and N.H. Shah2; 1University of Pennsylvania, Philadelphia, PA, 2Stanford University, Stanford, CA Purpose/Objective(s): Androgen deprivation therapy (ADT) is a mainstay of treatment for prostate cancer. While most individuals return to normal testosterone levels following treatment, 20% to 30% have prolonged androgen suppression. Concerningly, androgens have been shown to aid in neuron growth and axonal regeneration with multiple studies showing an association between ADT and cognitive dysfunction. In the current analysis we utilize an informatics approach using electronic medical record data from more than 1.2 million patients to examine the association of ADT with the subsequent development of dementia among men with prostate cancer. Materials/Methods: We used a previously validated and implemented text-processing pipeline to analyze electronic medical record data in a retrospective cohort of patients. We extracted International Classification of Diseases-9th (ICD-9) revision diagnosis and Current Procedural Terminology codes, medication lists, and positive-present mentions of drug and disease concepts from all clinical notes. New-onset dementia was defined using terms from clinical notes and ICD-9 diagnostic codes 290.0290.9, 331.0-331.2, and 294.1-294.21. We then tested the effect of ADT on risk of dementia using 1:5 propensity scoreematched and traditional Cox proportional hazards models. Traditional models were adjusted for age at prostate cancer diagnosis, race, smoking status, use of antiplatelet, anticoagulant, antihypertensive, and statin medications, and a history of cardiovascular disease, diabetes, or malignancy. We also tested whether the duration of ADT use was association with dementia risk. Results: There were 9,501 men with prostate cancer meeting all study criteria with 1,921 (20.2%) receiving ADT. During a median follow-up period of 4.6 years (interquartile range, 0.9-7.1 years) 297 patients were diagnosed with dementia. Propensity scoreematched analysis (hazard ratio, 1.64; 95% CI Z 1.20 to 2.23; P Z 0.002) and traditional multivariable Cox regression analysis (hazard ratio, 1.81; 95% CI Z 1.39 to 2.37; P < 0.001) both supported a statistically significant association between ADT use and dementia risk. We also observed a statistically significant increased risk of dementia with increasing duration of ADT (P for trend < 0.001) with individuals undergoing ADT for greater than 1 year having the highest risk (hazard ratio, 1.96; 95% CI Z 1.38 to 2.78; P < 0.001) in propensity scoreematched models. Conclusion: Our results support an association between the use of ADT in the treatment of prostate cancer and an increased risk of dementia in a general population cohort. Future prospective studies are needed to confirm this finding. Author Disclosure: K.T. Nead: None. G. Gaskin: None. C. Chester: None. S.D. Swisher-McClure: None. N.J. Leeper: None. N.H. Shah: Stock; Kyron, Apixio.