Difference In Prostate Cancer-specific Mortality Research Articles

Individual Patient Data Analysis of 17 Randomized Trials vs. Real-World Data for Men with Localized Prostate Cancer Receiving Radiotherapy.

Prior work has demonstrated poor correlation between the results of randomized controlled trials (RCTs) and real-world evidence (RWD). However, patients enrolled in RCTs are often considered to poorly represent the real-world population. Herein, we utilize multiple large data repositories to determine differences in baseline characteristics and long-term outcomes between patients enrolled in RCTs and RWD that received radiotherapy for localized prostate cancer. Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium was leveraged, and 17 phase III randomized trials were included. RWD were accessed through the Staging Collaboration for Cancer of the Prostate (STAR-CAP) cohort, a cohort that is comprised of >60 centers across the United States and Europe. Additionally, RWD was assessed via the Surveillance, Epidemiology, and End Results (SEER) database. MARCAP and STAR-CAP both contain outcomes for distant metastasis (DM), metastasis-free survival (MFS), prostate cancer-specific mortality (PCSM), and overall survival (OS). SEER only contains PCSM and OS. Wilcoxon signed-rank test and chi-square test were used to compare continuous and categorical variables, respectively. Inverse probability of treatment weighting (IPTW) analysis was conducted, balancing for age, PSA, Gleason score, T stage, and treatment year in the three cohorts. Cox and Fine-Gray regression models were used to compare disease outcomes between RCTs vs. RWD. Data from 10,666 patients from RCTs, 6,530 patients in STAR-CAP, and 117,586 patients in SEER were included. SEER patients were slightly younger (p<0.001, median age 68 (IQR 62-73) than those in RCTs (70, IQR 65-74) and in STAR-CAP (70, IQR 64-74). 10-year OS in RCTs was 65.4%, STAR-CAP 70.2%, SEER 64.1%. OS was superior in STAR-CAP (RCTs as reference; HR 0.91, 95% CI 0.85-0.96, p<0.0001), but there was no significant difference between SEER and RCTs (HR 0.96, 95% CI 0.91-1.02, p = 0.22). 10-year PCSM cumulative incidence was 7.4% in RCTs, 8.1% in STAR-CAP, and 11.0% in SEER. There was no significant difference in PCSM between STAR-CAP RWD and RCTs (HR 0.88, 95% CI 0.78-1.01, p = 0.08), whereas PCSM was worse in SEER than RCTs (HR 1.37, 95% CI 1.21-1.55, p<0.0001). There was no significant difference in DM between STAR-CAP RWD and RCTs (HR 0.93, 95% CI 0.83-1.04, p = 0.2). While baseline differences exist in patients enrolled on localized prostate cancer RCTs and real-world datasets, there were small if any significant relative differences in oncologic outcomes. This provides reassurance that RCT results are generally applicable to patients in routine practice.

Comparison of Intermittent and Continuous Androgen Deprivation Therapy in Prostate Cancer Patients: An Up-to-Date Meta-analysis for Urologists and Medical Providers.

Androgen deprivation therapy first became the treatment of choice for advanced prostate cancer in the 1940s with Charles Huggins' discoveries. Eight decades later, androgen deprivation therapy has significantly evolved, and yet is still utilized in various ways to treat certain forms of prostate cancer. For local recurrence after failed primary treatment and for locally advanced and metastatic disease, continuous androgen deprivation therapy has been standard of treatment. However, intermittent androgen deprivation therapy has emerged as a therapeutic alternative to continuous androgen deprivation therapy. The purpose of this meta-analysis is to provide an update on mortality, specifically prostate cancer-specific and nonprostate cancer causes, in order to offer some guidance when selecting the appropriate form of systemic androgen deprivation therapy. The PubMed database was searched for prospective randomized clinical trials. Inclusion and exclusion criteria were defined. Using statistical software, we analyzed random-effects models with the assumption that the data were randomly sampled, estimated the pooled log risk ratio, assessed heterogeneity, and created funnel plots to evaluate publication bias. A total of 12 randomized clinical trials met all inclusion criteria for final analysis. There was no statistically significant difference in prostate cancer-specific mortality between intermittent androgen deprivation therapy and continuous androgen deprivation therapy (RR=1.10 [0.85-1.42]). The analysis of nonprostate cancer mortality favored intermittent androgen deprivation therapy over continuous androgen deprivation therapy, but the difference was statistically insignificant (RR=0.94 [0.76-1.17]). These 2 treatment modalities can be considered as equivalent in long-term treatment outcomes. As intermittent androgen deprivation therapy is more cost-efficient and less likely to yield adverse side effects, future treatment guidelines should consider these advantages over continuous androgen deprivation therapy.

Effect of type of definitive treatment on race-based differences in prostate cancer-specific survival.

Racial and ethnic disparities in prostate cancer (PCa)mortality are partially mediated by inequities in quality of care. Intermediate- and high-risk PCa can be treated with either surgery or radiation, therefore we designed a study to assess the magnitude of race-based differences in cancer-specific survival between these two treatment modalities. Non-HispanicBlack (NHB)and non-HispanicWhite (NHW)men with localized intermediate- and high-risk PCa, treated with surgery or radiation between 2004 and 2015 in the Surveillance, Epidemiologyand End Results database were included in the study and followed until December 2018. Unadjusted and adjusted survival analyses were employed to compare cancer-specific survival by race and treatment modality. A model with an interaction term between race and treatment was used to assess whether the type of treatment amplified or attenuated the effect of race/ethnicity on prostate cancer-specific mortality (PCSM). 15,178 (20.1%) NHB and 60,225 (79.9%) NHW men were included in the study. NHB men had a higher cumulative incidence of PCSM (p = 0.005) and were significantly more likely to be treated with radiation than NHW men (aOR: 1.89, 95% CI: 1.81-1.97,p < 0.001). In the adjusted models, NHB men were significantly more likely to die from PCa compared withNHW men (aHR: 1.18,95% CI:1.03-1.35, p = 0.014), and radiation was associated with a significantly higher odds of PCSM (aHR: 2.10,95% CI:1.85-2.38, p < 0.001) compared with surgery. Finally, the interaction between race and treatment on PCSM was not significant, meaning that no race-based differences in PCSM were found within each treatment modality. NHB men with intermediate- and high-risk PCa had a higher rate of PCSM than NWH men in a large national cancer registry, though NHB and NHW men managed with the same treatment achieved similar PCa survival outcomes. The higher tendency for NHB men to receive radiation was similar in magnitude to the difference in cancer survival between racial and ethnic groups.

MP77-17 EFFECT OF TYPE OF DEFINITIVE TREATMENT ON RACE-BASED DIFFERENCES IN PROSTATE CANCER-SPECIFIC SURVIVAL

You have accessJournal of UrologyCME1 Apr 2023MP77-17 EFFECT OF TYPE OF DEFINITIVE TREATMENT ON RACE-BASED DIFFERENCES IN PROSTATE CANCER-SPECIFIC SURVIVAL Nicola Frego, Muhieddine Labban, Benjamin V. Stone, Mara Koelker, Khalid Alkhatib, Dejan K. Filipas, Edoardo Beatrici, Giovanni Lughezzani, Nicolò Maria Buffi, Stuart R. Lipsitz, Joel S. Weissman, Sean A. Fletcher, Adam S. Kibel, Quoc-Dien Trinh, and Alexander P. Cole Nicola FregoNicola Frego More articles by this author , Muhieddine LabbanMuhieddine Labban More articles by this author , Benjamin V. StoneBenjamin V. Stone More articles by this author , Mara KoelkerMara Koelker More articles by this author , Khalid AlkhatibKhalid Alkhatib More articles by this author , Dejan K. FilipasDejan K. Filipas More articles by this author , Edoardo BeatriciEdoardo Beatrici More articles by this author , Giovanni LughezzaniGiovanni Lughezzani More articles by this author , Nicolò Maria BuffiNicolò Maria Buffi More articles by this author , Stuart R. LipsitzStuart R. Lipsitz More articles by this author , Joel S. WeissmanJoel S. Weissman More articles by this author , Sean A. FletcherSean A. Fletcher More articles by this author , Adam S. KibelAdam S. Kibel More articles by this author , Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author , and Alexander P. ColeAlexander P. Cole More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Racial and ethnic disparities in prostate cancer (PCa) mortality are partially mediated by inequities in quality of care. Intermediate- and high-risk PCa can be treated with either surgery or radiation. We sought to assess the magnitude of race-based differences in cancer-specific survival between these treatment modalities. METHODS: NHB and non-Hispanic White (NHW) men with localized intermediate- and high-risk PCa, treated with surgery or radiation between 2004 and 2015 in the Surveillance, Epidemiology and End Results database were included in the study. Follow up was to December 2018. Unadjusted Kaplan-Meier curves and adjusted Fine-Gray competing-risks regression analyses with other cause of death as competing event, were employed to compare cancer-specific survival by race and treatment modality. A model with an interaction term between race and treatment was used to assess whether the type of treatment amplified or attenuated the effect of race on prostate cancer-specific mortality (PCSM). RESULTS: 15,178 (20,1%) NHB and 60,225 (79.9%) NHW men were included in the study. NHB men had a higher cumulative incidence of PCSM (p=0.005 by log-rank test) and were significantly less likely to be treated with surgery than NHW men (aOR:0.53, 95%CIs:0.51–0.55, p<0.001). In the adjusted models, NHB men were not significantly more likely to die for PCa compared to NHW men (aHR:1.11, 95%CIs:0.97-1.27, p=0.123); while radiation was associated with a significantly higher odds of PCSM (aHR:2.03, 95%CIs:1.79-2.31, p<0.001) compared to surgery. Finally, the interaction between race and treatment on PCSM was not significant (pint=0.073), meaning that no race-based differences in PCSM were found within each treatment modality. Indeed, we found no significant difference in PCSM when comparing NHB vs. NHW men treated with surgery (aHR:1.25, 95%CIs:0.97–1.63, p=0.086) or radiation (aHR:0.95, 95%CI:0.82–1.11, p=056). CONCLUSIONS: NHB and NHW men managed with the same treatment achieved similar PCa survival outcomes in a large national cancer registry. The higher tendency for NHB men to receive radiation was similar in magnitude to the difference in cancer survival between racial and ethnic groups. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1109 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicola Frego More articles by this author Muhieddine Labban More articles by this author Benjamin V. Stone More articles by this author Mara Koelker More articles by this author Khalid Alkhatib More articles by this author Dejan K. Filipas More articles by this author Edoardo Beatrici More articles by this author Giovanni Lughezzani More articles by this author Nicolò Maria Buffi More articles by this author Stuart R. Lipsitz More articles by this author Joel S. Weissman More articles by this author Sean A. Fletcher More articles by this author Adam S. Kibel More articles by this author Quoc-Dien Trinh More articles by this author Alexander P. Cole More articles by this author Expand All Advertisement PDF downloadLoading ...

PD20-08 TRENDS IN PROSTATE CANCER SPECIFIC MORTALITY BY RACE OVER TIME: A SEER ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023PD20-08 TRENDS IN PROSTATE CANCER SPECIFIC MORTALITY BY RACE OVER TIME: A SEER ANALYSIS Davuluri Meenakshi, Gina Demeo, Himanshu Nagar, Leonardo Borregales, and Jim Hu Davuluri MeenakshiDavuluri Meenakshi More articles by this author , Gina DemeoGina Demeo More articles by this author , Himanshu NagarHimanshu Nagar More articles by this author , Leonardo BorregalesLeonardo Borregales More articles by this author , and Jim HuJim Hu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003286.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: It has been demonstrated there was an increase in metastatic prostate cancer diagnosis from 2004 to 2013 in a previous SEER analysis. Our goal was to evaluate trends in prostate cancer specific mortality (PCSM) during this time period to determine if increased metastatic disease correlated with increased mortality rates. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) registry database, we identified men diagnosed with prostate cancer from 2004-2013. Men were stratified by age at diagnosis, race (White, Black, Hispanic, Asian, Native American, and Other), and stage at diagnosis. Number of deaths were identified and PCSM mortality was calculated. Descriptive statistics were used. RESULTS: We identified 497,166 men in SEER who met our inclusion criteria from 2004-2013. In this time period, the overall cohort PCSM decreased from 9.65% in 2004 to 5.95% in 2013 (Figure 1). We then stratified PCSM by race (Figure 2). We found that across all races PCSM decreased from 2004 to 2013 with the largest decrease in Native American men (18.0% to 10.4%) followed by Black men (11.6% to 7.0%). We further sub-stratified PCSM for men with distant metastasis at time of diagnosis (Figure 3). In this cohort of men, again a decrease in PCSM across all races was seen. The differences in PCSM from 2004 to 2013 are 3.9%, 8.9%, 5.9%, 13.2% and 22.8% for White, Black, Hispanic, Asian, and Native American men respectively. The largest decrease of PCSM was seen in Native American men with a 22% reduction of death rates in men diagnosed with metastatic disease from 2004 to 2013. CONCLUSIONS: PCSM has decreased overtime despite previous findings of increasing metastatic disease at time of diagnosis. This may be due to improved treatment options for metastatic disease. PCSM has decreased across all races, however Native American and Black men continue to have higher rates PCSM compared to other races. As more interventions are implemented to address disparities, longitudinal studies will be required to determine the impacts on survival outcomes. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e586 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Davuluri Meenakshi More articles by this author Gina Demeo More articles by this author Himanshu Nagar More articles by this author Leonardo Borregales More articles by this author Jim Hu More articles by this author Expand All Advertisement PDF downloadLoading ...

Social determinants of health (SDOH) and survival among patients with metastatic prostate cancer (mPC): A systematic literature review (SLR).

25 Background: Population level data show strong associations between race and other SDOH including income, education, and geographic region of residence. The relationship between SDOH and clinical outcomes has become increasingly recognized. This review examines the impact of SDOH on survival in patients with mPC in real-world (RW) settings. Methods: A systematic literature search in accordance with Cochrane guidelines was conducted on July 7, 2022, searching for RW studies published as full-text (Jan 2012-July 2022) and conferences (Jan 2019-July 2022) using Ovid MEDLINE, Embase, and Cochrane. A manual search of key congress websites for conference abstracts was also conducted. Studies which assessed the impact of SDOHs on survival, treatment access, and other clinical outcomes in patients with mPC were included in the overall SLR. Here, we present results from studies which assessed the impact of SDOH on overall survival (OS) and prostate cancer specific mortality (PCSM). Clinical trials were excluded. Results: Of 3,228 records screened, 86 studies were included, with findings reported in 67 full-text publications (60 US and 7 ex-US) and 28 conference abstracts (22 US and 6 ex-US). The impact of race on survival was reported in 54 studies. While most studies showed no difference between Black vs White for both OS (n=22) and PCSM (n=8), for patients on specific mPC treatments, there was an association between Black race and improved OS (n=5). Asian patients had improved OS vs White patients (n=4), and reduced PCSM vs White (n=6) and Black patients (n=1). Higher income was generally associated with improved OS (n=7), but no difference in PCSM (n=3). Although the regions compared differed, most studies found disparities in OS among US geographic regions (n=5). Education level was generally not associated with OS (n=2) or PCSM (n=3). Most studies showed that married patients had improved OS (n=4) and reduced PCSM (n=3) compared to unmarried patients. Conclusions: This SLR demonstrated that various SDOH are associated with disparities in survival among mPC patients. Asian race, which is generally associated with higher frequency of better SDOH risk factors, was linked with better OS. In contrast, Black race, which is generally associated with higher frequency of worse SDOH risk factors, was associated with similar or better OS. Having lower income and being unmarried were both associated with reduced OS, while disparities in OS were reported across geographic regions of the US. More studies are needed to understand why SDOH are linked with poor outcomes, including their connection with access to care.

Evaluation of Social Determinants of Health and Prostate Cancer Outcomes Among Black and White Patients

As the field of medicine strives for equity in care, research showing the association of social determinants of health (SDOH) with poorer health care outcomes is needed to better inform quality improvement strategies. To evaluate the association of SDOH with prostate cancer-specific mortality (PCSM) and overall survival (OS) among Black and White patients with prostate cancer. A MEDLINE search was performed of prostate cancer comparative effectiveness research from January 1, 1960, to June 5, 2020. Two authors independently selected studies conducted among patients within the United States and performed comparative outcome analysis between Black and White patients. Studies were required to report time-to-event outcomes. A total of 251 studies were identified for review. Three authors independently screened and extracted data. End point meta-analyses were performed using both fixed-effects and random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed, and 2 authors independently reviewed all steps. All conflicts were resolved by consensus. The primary outcome was PCSM, and the secondary outcome was OS. With the US Department of Health and Human Services Healthy People 2030 initiative, an SDOH scoring system was incorporated to evaluate the association of SDOH with the predefined end points. The covariables included in the scoring system were age, comorbidities, insurance status, income status, extent of disease, geography, standardized treatment, and equitable and harmonized insurance benefits. The scoring system was discretized into 3 categories: high (≥10 points), intermediate (5-9 points), and low (<5 points). The 47 studies identified comprised 1 019 908 patients (176 028 Black men and 843 880 White men; median age, 66.4 years [IQR, 64.8-69.0 years]). The median follow-up was 66.0 months (IQR, 41.5-91.4 months). Pooled estimates found no statistically significant difference in PCSM for Black patients compared with White patients (hazard ratio [HR], 1.08 [95% CI, 0.99-1.19]; P = .08); results were similar for OS (HR, 1.01 [95% CI, 0.95-1.07]; P = .68). There was a significant race-SDOH interaction for both PCSM (regression coefficient, -0.041 [95% CI, -0.059 to 0.023]; P < .001) and OS (meta-regression coefficient, -0.017 [95% CI, -0.033 to -0.002]; P = .03). In studies with minimal accounting for SDOH (<5-point score), Black patients had significantly higher PCSM compared with White patients (HR, 1.29; 95% CI, 1.17-1.41; P < .001). In studies with greater accounting for SDOH variables (≥10-point score), PCSM was significantly lower among Black patients compared with White patients (HR, 0.86; 95% CI, 0.77-0.96; P = .02). The findings of this meta-analysis suggest that there is a significant interaction between race and SDOH with respect to PCSM and OS among men with prostate cancer. Incorporating SDOH variables into data collection and analyses are vital to developing strategies for achieving equity.

Association between health-care system and prostate cancer mortality for African American men with localized and metastatic prostate cancer.

27 Background: African American (AA) men with prostate cancer (PC) present with more advanced disease and have worse survival than comparable non-Hispanic White (White) men. Recent studies suggest that receiving care within an equal access setting may attenuate these disparities. We hypothesize that AA men receiving care within the Veterans Health Administration (VHA) will have improved outcomes compared to AA men receiving care in the general population as assessed by the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We identified AA men diagnosed with PC between 2004 and 2015 in the VHA and SEER. For comparisons of covariate distributions across subgroups, we used the chi-squared test with continuity correction. We analyzed the cumulative incidence (with 95% confidence intervals (CIs)) of PC specific mortality (PCSM) in the VHA and SEER. Additionally, multivariable Cox proportional hazards models controlling for demographic information were performed. Results: The cohort included 85,409 AA men (VHA: 27,415, SEER: 57,994). Median follow-up was 4.79 years in the VHA and 5.16 years in SEER. In the VHA, AA men were more likely to present with localized disease (VHA 94.7% vs SEER 86.4%, p &lt; 0.001) and less likely to have metastatic disease (3.2% vs 4.3%, p &lt; 0.001). The 5-year cumulative incidence of PCSM was lower for patients in the VHA (VHA: 3.8% [CI: 3.5-4.1%] vs. SEER: 5.0% [CI: 4.8-5.2%], p &lt; 0.001). The PCSM difference was largest in men with metastatic disease. In metastatic patients, cumulative incidence of PCSM at five years was significantly lower in the VHA (VHA 52.5% [CI: 48.0-56.5%] vs. SEER 64.8% [CI: 62.3-67.1%], p &lt; 0.001). In contrast, AA men with localized disease had similar PCSM in the VHA and SEER (VHA 2.4% [CI: 2.2-2.6%] vs. SEER 2.6% [CI: 2.4-2.7%], p = 0.09 at five years). On multivariable analysis, VHA system was associated with lower PCSM [Hazard Ratio (HR): 0.91, p &lt; 0.001]. There was a significant interaction between VHA system and distant metastases at diagnosis [p &lt; 0.001] indicating larger differences in PCSM by healthcare system in metastatic patients as compared to localized patients. VHA system was associated with reduced PCSM in metastatic patients [HR 0.84, p &lt; 0.001] but not in localized patients [HR 0.96, p = 0.13]. Conclusions: AA men in the VHA had a significantly lower incidence of PCSM than those in the SEER database, especially for those who presented with distant metastases at diagnosis. Future work should examine how cost and access to care affect disparities in outcomes for AA men.

Conventional dose versus dose escalated radiotherapy including high-dose-rate brachytherapy boost for patients with Gleason score 9\u201310 clinical localized prostate cancer

As several recent researches focus on the importance of Gleason 9–10, we examine the role of radiotherapy dose escalation in those patients. We analyzed 476 patients with Gleason score 9–10 prostate cancer treated with radiotherapy. Of them, 127 patients were treated with conventional-dose external beam radiotherapy (Conv RT) and 349 patients were treated with high-dose radiotherapy (HDRT; 249 patients received high-dose-rate brachytherapy boost + external beam radiotherapy [HDR boost] and 100 patients received intensity-modulated radiotherapy [IMRT]). We compared these treatment groups using multi-institutional retrospective data. The patients had a median follow-up period of 66.3 months. HDRT showed superior biochemical disease-free survival (bDFS) rate (85.2%; HDR boost 84.7% and IMRT 86.6%) to Conv RT (71.1%, p < 0.0001) at 5 years, with a hazard ratio of 0.448. There were borderline difference in prostate cancer-specific mortality (PCSM; 4.3% and 2.75%, p = 0.0581), and distant metastasis-free survival (DMFS; 94.4% and 89.6%, p = 0.0916) rates at 5-years between Conv RT and HDRT group. Dose escalated radiotherapy showed better bDFS, borderline improvement in PCSM, and equivocal outcome in DMFS in with clinically localized Gleason 9–10 prostate cancer.

Long-term outcomes of two ablation techniques for treatment of radio-recurrent prostate cancer.

In men with recurrence of prostate cancer post radiation therapy, further treatment remains a challenge. The default salvage option of androgen-deprivation therapy (ADT) has adverse effects. Alternatively, selected men may be offered salvage therapy to the prostate. Herein, we present long-term oncological outcomes of two whole-gland ablation techniques, cryotherapy (sCT) and high-intensity-focused ultrasound (sHIFU). Men undergoing sCT (1995-2004) and sHIFU (2006-2018) at Western University were identified. Oncological endpoints included biochemical recurrence (BCR), ADT initiation, metastases, castration resistance (CRPC), and prostate cancer-specific mortality (PCSM). Survival analysis with competing risks of mortality was performed. Multivariable analysis was performed using Fine and Gray regression. A total of 187 men underwent sCT and 113 sHIFU. Mean (SD) age of the entire cohort was 69.9 (5.9 years), median pre-radiation PSA 9.6 ng/ml (IQR 6.1-15.2), and pre-salvage PSA 4.5 ng/ml (IQR 2.8-7.0). Median total follow-up was 116 months (IQR 67.5-173.8). A total of 170 (57.6%) developed BCR, 68 (23.4%) metastases, 143 (49.3%) were started on ADT, 58 (20.1%) developed CRPC, and 162 (56%) patients died of which 59 (36.4%) were of prostate cancer. On multivariable analysis, sHIFU (HR 1.65, 95% CI 1.15-2.36, p = 0.006) and pre-salvage PSA (HR 1.09, 95% CI 1.06-1.13, p < 0.0001) were associated with a higher risk of BCR. Similarly, sHIFU patients had a higher risk of CRPC (HR 2.31, 95% CI 1.23-4.35, p = 0.009). The cumulative incidence (for both treatments) of PCSM was 16.5% (95% CI 12.2-21.4%) at 10 years and 28.4% (95% CI 22.1-34.9%) at 20 years, with no difference between treatment modalities. Pre-salvage PSA was a common predictor for the measured oncological outcomes. Although sHIFU had higher BCR and CRPC rates, there were no differences in PCSM when compared with sCT. The long-term oncological data on two ablation techniques highlighted that only 50% of patients started ADT after 10-year follow-up.

PD63-03 TREATMENT INTENSIFICATION AND OUTCOME IN HIGH-RISK PROSTATE CANCER:A MULTI-INSTITUTIONAL CONSORTIUM ANALYSIS

INTRODUCTION AND OBJECTIVE:External beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), EBRT with a brachytherapy boost (EBRT+BT) with ADT, and radical prostatectomy (RP) with or with...

Geographic Distribution of Racial Differences in Prostate Cancer Mortality

While racial disparities in prostate cancer mortality are well documented, it is not well known how these disparities vary geographically within the US. To characterize geographic variation in prostate cancer-specific mortality differences between black and white men. This cohort study included data from 17 geographic registries within the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2007, to December 31, 2014. Inclusion criteria were men 18 years and older with biopsy-confirmed prostate cancer. Men missing data on key variables (ie, cancer stage, Gleason grade group, prostate-specific antigen level, and survival follow-up data) were excluded. Analysis was performed from September 5 to December 25, 2018. Patient SEER-designated race (ie, black, white, or other). Fine and Gray competing-risks regression analyses were used to evaluate the difference in prostate-cancer specific mortality between black and white men. A stratified analysis by Gleason grade group was performed stratified as grade group 1 and grade groups 2 through 5. The final cohort consisted of 229 771 men, including 178 204 white men (77.6%), 35 006 black men (15.2%), and 16 561 men of other or unknown race (7.2%). Mean (SD) age at diagnosis was 64.9 (8.8) years. There were 4773 prostate cancer deaths among white men and 1250 prostate cancer deaths among black men. Compared with white men, black men had a higher risk of mortality overall (adjusted hazard ratio [AHR], 1.39 [95% CI, 1.30-1.48]). In the stratified analysis, there were 4 registries in which black men had worse prostate cancer-specific survival in both Gleason grade group 1 (Atlanta, Georgia: AHR, 5.49 [95% CI, 2.03-14.87]; Greater Georgia: AHR, 1.88 [95% CI, 1.10-3.22]; Louisiana: AHR, 1.80 [95% CI, 1.06-3.07]; New Jersey: AHR, 2.60 [95% CI, 1.53-4.40]) and Gleason grade groups 2 through 5 (Atlanta: AHR, 1.88 [95% CI, 1.46-2.45]; Greater Georgia: AHR, 1.29 [95% CI, 1.07-1.56]; Louisiana: AHR, 1.28 [95% CI, 1.07-1.54]; New Jersey: AHR, 1.52 [95% CI, 1.24-1.87]), although the magnitude of survival difference was lower than for Gleason grade group 1 in each of these registries. The greatest race-based survival difference for men with Gleason grade group 1 disease was in the Atlanta registry. These findings suggest that population-level differences in prostate cancer survival among black and white men were associated with a small set of geographic areas and with low-risk prostate cancer. Targeted interventions in these areas may help to mitigate prostate cancer care disparities at the national level.

18-year prostate cancer-specific mortality after prostatectomy, brachytherapy, external beam radiation therapy, hormonal therapy, or monitoring for localized prostate cancer.

300 Background: The optimal treatment of localized prostate cancer (PCa) remains controversial. We compared long-term survival among men who underwent radical prostatectomy (RP), brachytherapy (BT), external beam radiation therapy (EBRT), primary androgen deprivation therapy (PADT), or monitoring (AS/WW) for localized PCa. Methods: Within the CaPSURE registry, we analyzed 12,062 men with localized PCa. PCa risk was assessed using the Stephenson preoperative nomogram and the Cancer of the Prostate Risk Assessment (CAPRA) score. Multivariable analyses were performed to compare prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) by primary treatment, adjusting for age and case-mix. An inverse probability weighted regression adjustment was used to reflect propensity for treatment assignment and any imbalances in censoring. Results: 6,357 men (53%) underwent RP, 1,351 (11%) BT, 1,716 (14%) EBRT, 1,605 (13%) PADT, and 1,033 (9%) AS/WW. During the 18-year follow-up period, 514 men died from PCa. Adjusting for clinical CAPRA score, the hazard ratios for PCSM relative to RP were 1.46 (95% CI, 1.00-2.12, p=0.050) for BT, 1.81 (95% CI, 1.43-2.30, p&lt;0.001) for EBRT, 2.77 (95% CI, 2.18-3.51, p&lt;0.001) for PADT, and 1.81 (95% CI, 1.23-2.66, p=0.003) for AS/WW. The greatest difference in PCSM between treatment modalities was observed for high-risk patients. Adjusting for age, comorbidity, and clinical CAPRA score, the hazard ratios for ACM were 1.46 (95% CI, 1.28-1.67) for BT, 1.38 (95% CI, 1.24-1.54) for EBRT, 1.89 (95% CI, 1.67-2.13) for PADT, and 1.60 (95% CI, 1.39-1.84) for AS/WW compared to RP (all p&lt;0.001). Additional analyses using 100-Stephenson score or Fine-Gray competing risks analysis demonstrated similar results. Conclusions: In a large, prospective cohort of men with localized PCa, after adjustment for age and comorbidity, risk of PCSM and ACM was lowest after RP. Mortality was significantly higher after EBRT and AS/WW, and highest after PADT. RP should be offered as part of the management paradigm for high-risk disease, AS/WW should be preferred for most low-risk PCa.

Associations among statins, preventive care, and prostate cancer mortality

Increasing evidence indicates an association between statins and reduced prostate cancer-specific mortality (PCSM). However, significant bias may exist in these studies. One particularly challenging bias to assess is the healthy user effect, which may be quantified by screening patterns. We aimed to evaluate the association between statin use, screening, and PCSM in a dataset with detailed longitudinal information. We used the Veterans Affairs Informatics and Computing Infrastructure to assemble a cohort of patients diagnosed with prostate cancer (PC) between 2000 and 2015. We collected patient-level demographic, comorbidity, and tumor data. We also assessed markers of preventive care utilization including cholesterol and prostate specific antigen (PSA) screening rates. Patients were considered prediagnosis statin users if they had at least one prescription one or more years prior to PC diagnosis. We evaluated PCSM using hierarchical Fine-Gray regression models and all-cause mortality (ACM) using a cox regression model. The final cohort contained 68,432 men including 40,772 (59.6%) prediagnosis statin users and 27,660 (40.4%) nonusers. Prediagnosis statin users had higher screening rates than nonusers for cholesterol (90 vs. 69%, p < 0.001) and PSA (76 vs. 67%, p < 0.001). In the model which excluded screening, prediagnosis statin users had improved PCSM (SHR 0.90, 95% CI 0.84-0.97; p = 0.004) and ACM (HR 0.96, 95% CI 0.93-0.99; p = 0.02). However, after including cholesterol and PSA screening rates, prediagnosis statin users and nonusers showed no differences in PCSM (SHR 0.98, 95% CI 0.91-1.06; p = 0.59) or ACM (HR 1.02, 95% CI 0.98-1.05; p = 0.25). We found that statin users tend to have more screening than nonusers. When we considered screening utilization, we observed no relationship between statin use before a prostate cancer diagnosis and prostate cancer mortality.

Prostate Cancer Outcomes Following Solid-Organ Transplantation: A SEER-Medicare Analysis.

Immunosuppressive regimens associated with organ transplantation increase the risk of developing cancer. Transplant candidates and recipients with prostate cancer are often treated, even if low-risk features would ordinarily justify active surveillance. Using SEER-Medicare, we identified 163 676 men aged 66 years and older diagnosed with nonmetastatic prostate cancer. History of solid organ transplant was identified using diagnosis or procedure codes. A propensity score-matched cohort was identified by matching transplanted men to nontransplanted controls by age, race, region, year, T-stage, grade, comorbidity, and cancer therapy. Fine-Gray competing risk models assessed associations between transplant status and prostate cancer-specific mortality (PCSM) and overall mortality (OM). We identified 620 men (0.4%) with transplant up to 10 years before (n = 320) or 5 years after (n = 300) prostate cancer diagnosis and matched them to 3100 men. At 10 years, OM was 55.7% and PCSM was 6.0% in the transplant cohort compared with 42.4% (P < .001) and 7.6% (P = .70) in the nontransplant cohort, respectively. Adjusted models showed no difference in PCSM for transplanted men (hazard ratio = 0.88, 95% confidence interval = 0.61 to 1.27, P = .70) or differences by prostate cancer therapy. Among 334 transplanted men with T1-2N0, well or moderately differentiated "low-risk" prostate cancer, PCSM was similar for treated and untreated men (hazard ratio = 0.92, 95% confidence interval = 0.47 to 1.81). Among men aged 66 years and older with prostate cancer, an organ transplant is associated with higher OM but no observable difference in PCSM. These findings suggest men with prostate cancer and previous or future organ transplantation should be managed per usual standards of care, including consideration of active surveillance for low-risk cancer characteristics.

Tobacco smoking and death from prostate cancer in US veterans.

Cigarette smoking is a risk factor for mortality in several genitourinary cancers, likely due to accumulation of carcinogens in urine. However, in prostate cancer (PC) the link has been less studied. We evaluated differences in prostate cancer-specific mortality (PCSM) between current smokers, past smokers, and never smokers diagnosed with PC. This was a retrospective cohort study of PCSM in men diagnosed with PC between 2000 and 2015 treated in the US Veterans Affairs health care system, using competing risk regression analyses. The cohort included 73,668 men (current smokers: 22,608 (30.7%), past smokers: 23,695 (32.1%), and never smokers: 27,365 (37.1%)). Median follow-up was 5.9 years. Current smoker patients were younger at presentation (median age current: 63, never: 66; p < 0.001), and had more advanced disease stage (stage IV disease current: 5.3%, never: 4.3%; p < 0.04). The 10-year incidence of PCSM was 5.2%, 4.8%, and 4.5% for current, past, and never smokers, respectively. On competing risk regression, current smoking was associated with increased PCSM (subdistribution hazard ratio: 1.14, 95% confidence interval: (1.05-1.24), p = 0.002), whereas past smoking was not. Hierarchical regression suggests that this increased risk was partially attributable to tumor characteristics. Smoking at the time of diagnosis is associated with a higher risk of dying from PC as well as other causes of death. In contrast, past smoking was not associated with PCSM suggesting that smoking may be a modifiable risk factor. PC diagnosis may be an important opportunity to discuss smoking cessation.

Clinical Outcomes among Patients with Radiorecurrent Gleason Grade Group 5 Prostate Cancer: Impact of Initial Treatment Strategy

Treatment with external beam radiation therapy (EBRT) + brachytherapy (BT) and androgen deprivation therapy (ADT) has been associated with lower prostate cancer (PCa)-specific mortality (PCSM) and longer time to distant metastasis (DM) compared with EBRT + ADT alone in Gleason grade group 5 (GG 5) PCa. However, outcomes are heterogeneous, and the addition of BT may also add toxicity. An alternative approach given the high competing risk of distant failure would be to treat with EBRT alone and reserve BT for local salvage if needed. However, it is unknown whether omitting the BT boost upfront might compromise the chance of cure. The purpose of this study is to examine the downstream ramifications of initial treatment selection in patients who developed biochemical recurrence (BCR) after EBRT or EBRT+BT. We hypothesized that upfront treatment intensification would still be associated with a benefit when restricting analysis to patients with BCR. Out of 1170 patients with GG 5 PCa treated at 12 institutions between 2000-2013 with definitive radiotherapy, we extracted data for 361 patients who experienced BCR by Phoenix criteria (n=84/436 with EBRT+BT, 277/734 with EBRT). Covariate-adjusted cumulative incidence rates for DM and PCSM were generated with Kaplan-Meier methods with inverse probability of treatment weights adjusting for age, Gleason score, initial PSA, T stage, and use of systemic salvage. Cox proportional hazards models with propensity scores included a covariate were used to compare DM and PCSM outcomes between treatment groups. Median follow-up was 6.6 and 6.0 years from initial treatment and 2.4 and 2.7 years from BCR, for EBRT+BT and EBRT, respectively. Median respective time to BCR was 3.2 and 3.0 years. Median duration of ADT was 12 months with EBRT+BT and 21 months with EBRT. Local salvage and systemic salvage treatment rates were 4.8% and 28.6% after EBRT+BT, and 5.4% and 31.8% after EBRT. From time of BCR, 3-year DM and PCSM rates were 52% and 33% after EBRT+BT and 59% and 30% after EBRT. Treatment with EBRT+BT was associated with a significantly longer time to DM (HR 0.63, 95% confidence interval (CI) 0.41-0.97, p=0.03) but was not associated with a difference in PCSM (HR 1.33, 95% CI 0.86-2.07, p=0.20). When focusing on patients who experienced BCR after definitive radiotherapy for GG 5 PCa, initial treatment with EBRT+BT vs EBRT was associated with significantly improved rates of DM. PCSM did not significantly differ between groups. Importantly, outcomes remain poor, and salvage treatments, particularly local salvage, appear underutilized. While limited by the relatively small numbers and retrospective design, these results imply that in the absence of improved salvage utilization in patients initially receiving EBRT+ADT, upfront treatment intensification with BT may translate to a delay in time to DM.

Survival Significance of Patients With Low Prostate-Specific Antigen and High-Grade Prostate Cancer After Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy.

Objective: This study compared survival of prostate cancer patients with low prostate specific antigen level (PSA ≤ 10 ng/ml) and high-grades of Gleason score (GS) of 8–10 with different treatment options (i.e., radical prostatectomy [RP], external beam radiotherapy [EBRT], or external beam radiotherapy with brachytherapy [EBRT+BT]).Materials and Methods: The Surveillance, Epidemiology and End Results (SEER) database data (2004–2013), and overall survival (OS) and prostate cancer-specific mortality (PCSM), were evaluated using the Cox proportional hazards regression model and Fine and Gray competing risk model.Results: The SEER data contained 9,114 patients, 4,175 of whom received RP, 4,114 received EBRT, and 825 received EBRT+BT with a median follow-up duration of 47 months. RP patients had significantly better OS than patients with EBRT and EBRT+BT (adjusted HR [AHR]: 3.36, 95% CI: 2.43–4.64, P < 0.001; AHR: 2.15, 95% CI: 1.32–3.48, P = 0.002; respectively). There was no statistical difference in PCSM between RP and EBRT+BT (AHR: 1.31, 95% CI: 0.61–2.80, P = 0.485), while EBRT had worse OS (P < 0.05). The subgroup analysis revealed that there was no statistical difference in prognosis of patients with age of >70 years old, or PSA levels of ≤ 2.5 ng/ml between RP and EBRT+BT (P > 0.05).Conclusion: RP patients with low PSA levels and high GS had better OS compared to either EBRT or EBRT+BT, while RP and EBRT+BT resulted in significantly lower PCSM, compared to EBRT. Moreover, EBRT+BT and RP were associated with similar survival of patients with age of > 70 years old, or PSA levels of ≤ 2.5 ng/ml.

The Influence of Ethnic Heterogeneity on Prostate Cancer Mortality After Radical Prostatectomy in Hispanic or Latino Men: A Population-based Analysis

To determine if recently found disparities in prostate cancer-specific mortality (PCSM) among Mexican and Puerto Rican men remained true in patients undergoing radical prostatectomy (RP), where the true grade and extent of cancer are known and can be accounted for. Men diagnosed with localized-regional prostate cancer who had undergone RP as primary treatment were identified (N = 180,794). Patients were divided into the following racial and ethnic groups: non-Hispanic white (NHW) (n = 135,358), non-Hispanic black (NHB) (n = 21,882), Hispanic or Latino (n = 15,559), and Asian American or Pacific Islander (n = 7995). Hispanic or Latino men were further categorized into the following subgroups: Mexican (n = 3323) and South or Central American, excluding Brazilian (n = 1296), Puerto Rican (n = 409), and Cuban (n = 218). A multivariable analysis was conducted using competing risk regression in the prediction of PCSM. This analysis revealed hidden disparities in surgical outcomes for prostate cancer. In the multivariable analysis, Hispanic or Latino men (hazard ratio [HR] = 0.88, P = .207) did not show a significant difference in PCSM compared with NHW men. When breaking Hispanic or Latino men into their country of origin or ancestry, Puerto Rican men were found to have significantly worse PCSM than NHW men (HR = 2.55, P = .004) and NHB men (HR = 2.33, P = .016). Our findings reveal higher rates of PCSM for Puerto Rican men after RP than for both NHW and NHB men. At a minimum, these findings need further validation and should be considered in the screening and management of these men.

Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer

The optimal treatment for Gleason score 9-10 prostate cancer is unknown. To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.