Differential use of medical versus surgical androgen deprivation therapy for patients with metastatic prostate cancer

Hala T. Borno, Daphne Y. Lichtensztajn, Scarlett L. Gomez, Nynikka R. Palmer, Charles J. Ryan

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Surgical and medical androgen deprivation therapy (ADT) strategies are comparable in their ability to suppress serum testosterone levels as treatment in patients with metastatic prostate cancer but differ with regard to cost and impact on quality of life. Medical ADT is associated with better long-term quality of life due to the flexibility of possible therapy interruption but comes with a higher cumulative cost. In the current study, the authors examined whether surgical ADT (ie, bilateral orchiectomy) was used differentially by race/ethnicity and other social factors. Methods: The authors identified patients with metastatic disease at the time of diagnosis through the California Cancer Registry. The association between race/ethnicity and receipt of surgical ADT was modeled using multivariable Firth logistic regression adjusting for age, Gleason score, prostate-specific antigen level, clinical tumor and lymph node classification, neighborhood socioeconomic status (SES), insurance, marital status, comorbidities, initial treatment (radiotherapy, chemotherapy), location of care, rural/urban area of residence, and year of diagnosis. Results: The authors examined a total of 10,675 patients with metastatic prostate cancer, 11.4% of whom were non-Hispanic black, 8.4% of whom were Asian/Pacific Islander, 18.5% of whom were Hispanic/Latino, and 60.5% of whom were non-Hispanic white. In the multivariable model, patients found to be more likely to receive surgical ADT were Hispanic/Latino (odds ratio [OR], 1.32; 95% confidence interval [95% CI], 1.01-1.72), were from a low neighborhood SES (OR, 1.96; 95% CI, 1.34-2.89) or rural area (OR, 1.49; 95% CI, 1.15-1.92), and had Medicaid/public insurance (OR, 2.21; 95% CI, 1.58-3.10). Patients with military/Veterans Affairs insurance were significantly less likely to receive surgical ADT compared with patients with private insurance (OR, 0.34; 95% CI, 0.13-0.88). Conclusions: Race/ethnicity, neighborhood SES, and insurance status appear to be significantly associated with receipt of surgical ADT. Future research will need to characterize other differences in initial treatments among men with advanced prostate cancer based on race/ethnicity and aim to better understand what factors drive the association between surgical ADT among men of Hispanic origin or those from areas with low neighborhood SES.

Original languageEnglish (US)
Pages (from-to)453-462
Number of pages10
JournalCancer
Volume125
Issue number3
DOIs
StatePublished - Feb 1 2019

Bibliographical note

Funding Information:
Supported in part by the National Cancer Institute?s Surveillance, Epidemiology, and End Results program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California. The collection of the cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute?s Surveillance, Epidemiology, and End Results program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention?s National Program of Cancer Registries under agreement U58DP003862-01 awarded to the California Department of Public Health. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, the Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their contractors and subcontractors is not intended nor should be inferred. Daphne Y. Lichtensztajn has received a grant from the National Cancer Institute?s Surveillance, Epidemiology, and End Results program for work performed as part of the current study and a grant from Shire Pharmaceuticals for work performed outside of the current study. In the overall model presented in Table regarding the outcome of bilateral orchiectomy as the form of ADT received (with those receiving medical ADT as the reference group), being of Hispanic ethnicity, being of older age, having lower neighborhood SES, having Medicaid/public insurance status, residing in a rural MSSA, and having unknown lymph node status were associated with an increased likelihood of receiving treatment with bilateral orchiectomy. Conversely, having organ-confined disease (<T3), having a PSA value of 10 to 20 ng/mL, having an unknown Gleason score, having military or Veterans Affairs insurance, being of unknown marital status, having an unknown Charlson Comorbidity Index, receipt of care at an NCI-designated cancer center, and having later years of diagnosis were found to be inversely associated with receipt of bilateral orchiectomy. Abbreviations: 95% CI, 95% confidence interval; ADT, androgen deprivation therapy; MSSA, Medical Service Study Area; NCI, National Cancer Institute; NH, non-Hispanic; NOS, not otherwise specified; OR, odds ratio; PI, Pacific Islander; PSA, prostate-specific antigen; SES, socioeconomic status; VA, Veterans Affairs. Bold type indicates statistical significance. Overall, we identified 10,675 men with metastatic prostate cancer at the time of diagnosis in California from 2004 through 2015. The patient characteristics of the study sample are summarized in Table. Of the men identified, 60.5% were NH white, 11.5% were NH black (black), 18.7% were Hispanic/Latino (Hispanic), and 8.1% were Asian/Pacific Islander (Asian). The majority of the sample were men aged ?65 years (72.7%), were married (56.1%), and resided in middle or high SES neighborhoods (63.1%). The majority of the sample were insured (94.1%) and nearly one-half of the men were covered by Medicare (47%). The median age of the study sample was 73 years (range, 29-105 years). The majority of the sample had a prostate biopsy performed (58.4%), with a histology type of adenocarcinoma (78.7%), a Gleason score of ?7 (57.1%), and a PSA level of >20 ng/mL at the time of diagnosis (70.2%). In addition, the majority received initial medical ADT (74.2%), without initial radiotherapy (80.2%) or initial chemotherapy (91.7%). A minority of the sample received care at an NCI-designated cancer center (11.7%) and in a rural/frontier medical service setting (15.5%). The study sample was relatively equally distributed by year of diagnosis. Abbreviations: ADT, androgen deprivation therapy; MSSA, Medical Service Study Area; NCI, National Cancer Institute; NH, non-Hispanic; NOS, not otherwise specified; PI, Pacific Islander; PSA, prostate-specific antigen; SES, socioeconomic status; VA, Veterans Affairs. The overwhelming majority of patients received medical ADT. However, differences based on the type of ADT received were noted across several demographic characteristics. In Table, the patient characteristics were stratified by type of ADT received (surgery vs medical). Compared with the group receiving medical ADT, there were higher percentages of Hispanic men, men living in lower SES neighborhoods or rural medical service areas, men with Medicare or Medicaid/public insurance, unmarried men, men with disease classified as ?cT3a, men with unknown lymph node status, and men with PSA levels ?20 ng/mL in the group of patients who received surgical ADT. The percentage of men with an unknown Charlson Comorbidity Index was significantly lower in the surgical ADT group. No differences in age at the time of diagnosis were noted by type of ADT received, with the median age being 73 years in both groups. In Figures A to D, we observed that the percentage of patients who received medical ADT increased over time across all insurance types, race/ethnicity, neighborhood SES, and rural versus urban settings. Abbreviations: ADT, androgen deprivation therapy; MSSA, Medical Service Study Area; NCI, National Cancer Institute; NH, non-Hispanic; NOS, not otherwise specified; PI, Pacific Islander; PSA, prostate-specific antigen; SES, socioeconomic status. Data for men with military or Veterans Affairs insurance (476 men) and other or unknown race (131 men) were not shown as per California Cancer Registry confidentiality policy. Overall, we identified 10,675 men with metastatic prostate cancer at the time of diagnosis in California from 2004 through 2015. The patient characteristics of the study sample are summarized in Table. Of the men identified, 60.5% were NH white, 11.5% were NH black (black), 18.7% were Hispanic/Latino (Hispanic), and 8.1% were Asian/Pacific Islander (Asian). The majority of the sample were men aged ?65 years (72.7%), were married (56.1%), and resided in middle or high SES neighborhoods (63.1%). The majority of the sample were insured (94.1%) and nearly one-half of the men were covered by Medicare (47%). The median age of the study sample was 73 years (range, 29-105 years). The majority of the sample had a prostate biopsy performed (58.4%), with a histology type of adenocarcinoma (78.7%), a Gleason score of ?7 (57.1%), and a PSA level of >20 ng/mL at the time of diagnosis (70.2%). In addition, the majority received initial medical ADT (74.2%), without initial radiotherapy (80.2%) or initial chemotherapy (91.7%). A minority of the sample received care at an NCI-designated cancer center (11.7%) and in a rural/frontier medical service setting (15.5%). The study sample was relatively equally distributed by year of diagnosis. Abbreviations: ADT, androgen deprivation therapy; MSSA, Medical Service Study Area; NCI, National Cancer Institute; NH, non-Hispanic; NOS, not otherwise specified; PI, Pacific Islander; PSA, prostate-specific antigen; SES, socioeconomic status; VA, Veterans Affairs. The overwhelming majority of patients received medical ADT. However, differences based on the type of ADT received were noted across several demographic characteristics. In Table, the patient characteristics were stratified by type of ADT received (surgery vs medical). Compared with the group receiving medical ADT, there were higher percentages of Hispanic men, men living in lower SES neighborhoods or rural medical service areas, men with Medicare or Medicaid/public insurance, unmarried men, men with disease classified as ?cT3a, men with unknown lymph node status, and men with PSA levels ?20 ng/mL in the group of patients who received surgical ADT. The percentage of men with an unknown Charlson Comorbidity Index was significantly lower in the surgical ADT group. No differences in age at the time of diagnosis were noted by type of ADT received, with the median age being 73 years in both groups. In Figures A to D, we observed that the percentage of patients who received medical ADT increased over time across all insurance types, race/ethnicity, neighborhood SES, and rural versus urban settings. Abbreviations: ADT, androgen deprivation therapy; MSSA, Medical Service Study Area; NCI, National Cancer Institute; NH, non-Hispanic; NOS, not otherwise specified; PI, Pacific Islander; PSA, prostate-specific antigen; SES, socioeconomic status. Data for men with military or Veterans Affairs insurance (476 men) and other or unknown race (131 men) were not shown as per California Cancer Registry confidentiality policy. In the overall model presented in Table regarding the outcome of bilateral orchiectomy as the form of ADT received (with those receiving medical ADT as the reference group), being of Hispanic ethnicity, being of older age, having lower neighborhood SES, having Medicaid/public insurance status, residing in a rural MSSA, and having unknown lymph node status were associated with an increased likelihood of receiving treatment with bilateral orchiectomy. Conversely, having organ-confined disease (<T3), having a PSA value of 10 to 20 ng/mL, having an unknown Gleason score, having military or Veterans Affairs insurance, being of unknown marital status, having an unknown Charlson Comorbidity Index, receipt of care at an NCI-designated cancer center, and having later years of diagnosis were found to be inversely associated with receipt of bilateral orchiectomy. Abbreviations: 95% CI, 95% confidence interval; ADT, androgen deprivation therapy; MSSA, Medical Service Study Area; NCI, National Cancer Institute; NH, non-Hispanic; NOS, not otherwise specified; OR, odds ratio; PI, Pacific Islander; PSA, prostate-specific antigen; SES, socioeconomic status; VA, Veterans Affairs. Bold type indicates statistical significance. The current study was an observational cohort study within the population-based California Cancer Registry (CCR), a state-mandated registry that has collected data regarding all cancers diagnosed in residents of California since 1988. The CCR, which comprises 3 regional registries that are members of the National Cancer Institute?s (NCI) Surveillance, Epidemiology, and End Results (SEER) program, abstracts information regarding patient demographics, tumor characteristics, and initial treatment. Data were obtained regarding all men with de novo metastatic prostate cancer at the time of diagnosis in California from 2004 through 2015, regardless of histologic subtype (13,875 men). Men diagnosed on death certificate or at the time of autopsy only (21 men) and those who did not receive any form of ADT (3179 men) were excluded from analysis. The current study was included under the approved institutional review board protocol for the Greater Bay Area cancer registries (SEER San Francisco/Oakland and San Jose/Monterey registries). The current study was an observational cohort study within the population-based California Cancer Registry (CCR), a state-mandated registry that has collected data regarding all cancers diagnosed in residents of California since 1988. The CCR, which comprises 3 regional registries that are members of the National Cancer Institute?s (NCI) Surveillance, Epidemiology, and End Results (SEER) program, abstracts information regarding patient demographics, tumor characteristics, and initial treatment. Data were obtained regarding all men with de novo metastatic prostate cancer at the time of diagnosis in California from 2004 through 2015, regardless of histologic subtype (13,875 men). Men diagnosed on death certificate or at the time of autopsy only (21 men) and those who did not receive any form of ADT (3179 men) were excluded from analysis. The current study was included under the approved institutional review board protocol for the Greater Bay Area cancer registries (SEER San Francisco/Oakland and San Jose/Monterey registries). The primary outcome of this analysis was receipt of bilateral orchiectomy (surgical ADT) as part of initial treatment among men with metastatic prostate cancer at the time of diagnosis. The CCR collects race and ethnicity data from medical records and in addition applies an established algorithm based on surname and birthplace to establish Hispanic ethnicity. Patients are categorized by race and ethnicity into the following groups: non-Hispanic (NH) white, NH black, Hispanic, Asian/Pacific Islander, and other/unknown. Marital status was categorized as married, unmarried, or unknown. Insurance status was categorized as uninsured/unknown, private, Medicaid, Medicare, or military/Veterans Affairs. The CCR does not collect data regarding individual-level measures of SES. However, because patients? addresses at the time of diagnosis routinely are geocoded by the CCR, we used a previously described composite measure of SES and assigned each case to a quintile of neighborhood SES based on the US Census block group. The Office of Statewide Health Planning and Development (OSHPD) uses population, demographic, and physician data to define Medical Service Study Areas (MSSAs), which are subcounty and subcity geographic areas composed of at least one census tract, and which can be used to characterize health professional shortage areas, medically underserved areas, and medically underserved populations. These MSSAs are characterized as urban, rural, or frontier based on population density. Each patient?s residence at the time of diagnosis was classified as being either in an urban or rural/frontier MSSA. In addition, we identified patients who received care at an NCI-designated cancer center. We grouped Gleason score into a Gleason score ?6, a Gleason score of 7, a Gleason score of 8 to 10, or an unknown Gleason score. We described tumor size using clinical T classification categories of ?T2a, T2b to T2c/T2NOS, ?T3a, or Tx. We summarized lymph node status using clinical N classification categories grouped as N0, N1, or Nx. We categorized prostate-specific antigen (PSA) values as <10 ng/mL, 10 to 20 ng/mL, >20 ng/mL, or unknown. We measured comorbidity burden using the Charlson Comorbidity Index derived from linking CCR data with the OSHPD discharge data. The Charlson Comorbidity Index is a weighted score categorized as 0 (no comorbidity), 1, 2, or ?3. The type of ADT received as part of the initial treatment was obtained from the CCR and categorized as no ADT, orchiectomy only, medical ADT only, both orchiectomy and medical ADT, or unknown. Both receipt of radiotherapy and chemotherapy as part of the initial treatment were dichotomized as yes or no. The use of ADT in men diagnosed with metastatic prostate cancer was characterized. Differences in characteristics between men who received surgical ADT and those who received medical ADT were compared using chi-square tests. The association between race/ethnicity and receipt of surgical ADT was modeled using Firth logistic regression (penalized likelihood method) to reduce small sample bias. Men who received both medical and surgical ADT were included with those who received only surgical ADT; men who had not received ADT (3179 men) were excluded from the current analysis. Covariates considered for inclusion in the multivariable model were age at the time of diagnosis, Gleason score, PSA value at the time of diagnosis, tumor size (T classification), lymph node involvement (N classification), quintile of neighborhood SES, primary health care payer, marital status, Charlson Comorbidity Index, receipt of other primary treatments (radiotherapy, chemotherapy), receipt of care at an NCI-designated cancer center, urban/rural designation of the OSHPD MSSA of the patient?s residence at the time of diagnosis, and year of diagnosis. Age at diagnosis and year of diagnosis were included as continuous variables; the remainder were included as categorical variables. A purposeful selection strategy was used to select variables for inclusion in the final multivariable model. All variables that were significant at the P?.25 level on univariate analysis initially were included in the multivariable model. The model was iteratively reduced, retaining only those variables with a P value <.10. Variables that were not initially included in the model then were added back and retained as significant confounders in the final model if they changed effect estimates by >20%. First-order interactions between race/ethnicity, neighborhood SES, insurance, and rural/urban status were tested and found not to be significant. We conducted sensitivity analyses to assess the effect of potential underascertainment of systemic hormone therapy, in which men for whom hormonal therapy was coded as ?none,? ?recommended, unknown if given,? or ?unknown? (1838 men) were considered as having received hormone therapy. All analyses were performed using SAS statistical software (version 9.4; SAS Institute Inc, Cary, North Carolina). Statistical tests were 2-sided, and values with P <.05 were considered to be statistically significant.

Funding Information:
Supported in part by the National Cancer Institute’s Surveillance, Epidemiology, and End Results program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California. The collection of the cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute’s Surveillance, Epidemiology, and End Results program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries under agreement U58DP003862-01 awarded to the California Department of Public Health. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, the Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their contractors and subcontractors is not intended nor should be inferred.

Funding Information:
Daphne Y. Lichtensztajn has received a grant from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program for work performed as part of the current study and a grant from Shire Pharmaceuticals for work performed outside of the current study.

Publisher Copyright:
© 2018 American Cancer Society

Keywords

  • androgen deprivation therapy (ADT)
  • cancer disparities
  • metastatic prostate cancer
  • orchiectomy

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