Andrew S. Hyatt

Association of androgen-deprivation therapy with excess cardiac-specific mortality in men with prostate cancer.

To determine if androgen‐deprivation therapy (ADT) is associated with excess cardiac‐specific mortality (CSM) in men with prostate cancer and no cardiovascular comorbidity, coronary artery disease risk factors, or congestive heart failure (CHF) or past myocardial infarction (MI).

Getting back to equal: The influence of insurance status on racial disparities in the treatment of African American men with high-risk prostate cancer.

OBJECTIVES Treating high-risk prostate cancer (CaP) with definitive therapy improves survival. We evaluated whether having health insurance reduces racial disparities in the use of definitive therapy for high-risk CaP. MATERIALS AND METHODS The Surveillance, Epidemiology, and End Results Program was used to identify 70,006 men with localized high-risk CaP (prostate-specific antigen level > 20 ng/ml or Gleason score 8-10 or stage > cT3a) diagnosed from 2007 to 2010. We used multivariable logistic regression to analyze the 64,277 patients with complete data to determine the factors associated with receipt of definitive therapy. RESULTS Compared with white men, African American (AA) men were significantly less likely to receive definitive treatment (adjusted odds ratio [AOR] = 0.60; 95% CI: 0.56-0.64; P < 0.001) after adjusting for sociodemographics and known CaP prognostic factors. There was a significant interaction between race and insurance status (P interaction = 0.01) such that insurance coverage was associated with a reduction in racial disparity between AA and white patients regarding receipt of definitive therapy. Specifically, the AOR for definitive treatment for AA vs. white was 0.38 (95% CI: 0.27-0.54, P < 0.001) among uninsured men, whereas the AOR was 0.62 (95% CI: 0.57-0.66, P < 0.001) among insured men. CONCLUSIONS AA men with high-risk CaP were significantly less likely to receive potentially life-saving definitive treatment when compared with white men. Having health insurance was associated with a reduction in this racial treatment disparity, suggesting that expansion of health insurance coverage may help reduce racial disparities in the management of aggressive cancers.

Income inequality and treatment of African American men with high-risk prostate cancer

PURPOSE Definitive treatment of high-risk prostate cancer with radical prostatectomy or radiation improves survival. We assessed whether racial disparities in the receipt of definitive therapy for prostate cancer vary by regional income. PATIENTS AND METHODS A cohort of 102,486 men (17,594 African American [AA] and 84,892 non-Hispanic white) with localized high-risk prostate cancer (prostate-specific antigen >20 ng/ml or Gleason ≥ 8 or stage ≥ cT2c) diagnosed from 2004 to 2010 was identified in the Surveillance, Epidemiology, and End Results database. Income was measured at the census-tract-level. We used multivariable logistic regression to assess patient and cancer characteristics associated with the receipt of definitive therapy for prostate cancer. Multivariable Fine and Gray competing risks analysis was used to evaluate factors associated with prostate cancer death. RESULTS Overall, AA men were less likely to receive definitive therapy than white men (adjusted odds ratio [AOR] = 0.51; 95% CI: 0.49-0.54; P<0.001), and there was a significant race/income interaction (Pinteraction = 0.016) such that there was a larger racial treatment disparity in the bottom income quintile (AOR = 0.49; 95% CI: 0.45-0.55; P<0.001) than in the top income quintile (AOR = 0.60; 95% CI: 0.51-0.71; P<0.001). After a median follow-up of 35 months, AA men in the bottom income quintile suffered the greatest prostate cancer mortality (adjusted hazard ratio = 1.47; 95% CI: 1.17-1.84; P = 0.001), compared with white men in the top income quintile. CONCLUSIONS Racial disparities in the receipt of definitive therapy for high-risk prostate cancer are greatest in low-income communities, suggesting that interventions to reduce racial disparities should target low-income populations first.

The association between insurance status and prostate cancer outcomes: implications for the Affordable Care Act

Background:The Affordable Care Act (ACA) aims to expand health insurance coverage to over 30 million previously uninsured Americans. To help evaluate the potential impact of the ACA on prostate cancer care, we examined the associations between insurance coverage and prostate cancer outcomes among men <65 years old who are not yet eligible for Medicare.Methods:The Surveillance, Epidemiology and End Results Program was used to identify 85 203 men aged <65 years diagnosed with prostate cancer from 2007 to 2010. Multivariable logistic regression modeled the association between insurance status and stage at presentation. Among men with high-risk disease, the associations between insurance status and receipt of definitive therapy, prostate cancer-specific mortality (PCSM) and all-cause mortality were determined using multivariable logistic, Fine and Gray competing-risks and Cox regression models, respectively.Results:Uninsured patients were more likely to be non-white and come from regions of rural residence, lower median household income and lower education level (P<0.001 for all cases). Insured men were less likely to present with metastatic disease (adjusted odds ratio (AOR) 0.23; 95% confidence interval (CI) 0.20–0.27; P<0.001). Among men with high-risk disease, insured men were more likely to receive definitive treatment (AOR 2.29; 95% CI 1.81–2.89; P<0.001), and had decreased PCSM (adjusted hazard ratio 0.56; 95% CI 0.31–0.98; P=0.04) and all-cause mortality (adjusted hazard ratio 0.60; 0.39–0.91; P=0.01).Conclusions:Insured men with prostate cancer are less likely to present with metastatic disease, more likely to be treated if they develop high-risk disease and are more likely to survive their cancer, suggesting that expanding health coverage under the ACA may significantly improve outcomes for men with prostate cancer who are not yet eligible for Medicare.

Racial disparities in prostate cancer-specific mortality in men with low-risk prostate cancer.

BACKGROUND Men with low-risk prostate cancer (CaP) are considered unlikely to die of CaP and have the option of active surveillance. This study evaluated whether African American (AA) men who present with low-risk disease are at higher risk for death from CaP than white men. PATIENTS AND METHODS The authors identified 56,045 men with low-risk CaP (T1-T2a, Gleason score ≤ 6, prostate-specific antigen ≤ 10 ng/mL) diagnosed between 2004 and 2009 using the Surveillance, Epidemiology, and End Results (SEER) database. Fine-Gray competing-risks regression analyses were used to analyze the effect of race on prostate cancer-specific mortality (PCSM) after adjusting for known prognostic and sociodemographic factors in 51,315 men (43,792 white; 7523 AA) with clinical follow-up information available. RESULTS After a median follow-up of 46 months, 258 patients (209 [0.48%] white and 49 [0.65%] AA men) died from CaP. Both AA race (adjusted hazard ratio [AHR], 1.45; 95% CI, 1.03-2.05; P = .032) and noncurative management (AHR, 1.49; 95% CI, 1.15-1.95; P = .003) were significantly associated with an increased risk of PCSM. When analyzing only patients who underwent curative treatment, AA race (AHR, 1.62; 95% CI, 1.04-2.53; P = .034) remained significantly associated with increased PCSM. CONCLUSION Among men with low-risk prostate cancer, AA race compared with white race was associated with a higher risk of PCSM, raising the possibility that clinicians may need to exercise caution when recommending active surveillance for AA men with low-risk disease. Further studies are needed to ultimately determine whether guidelines for active surveillance should take race into account.

Use of a rectal spacer with low-dose-rate brachytherapy for treatment of prostate cancer in previously irradiated patients: Initial experience and short-term results.

BACKGROUND Salvage brachytherapy in patients with prior pelvic radiation carries a risk of rectal injury. Herein, we report our initial experience using a hydrogel spacer between the prostate and the rectum during salvage brachytherapy. METHODS AND MATERIALS A total of 11 patients with prostate cancer and prior radiotherapy (5 prostate brachytherapy, 2 prostate external beam radiation therapy [EBRT], and 4 rectal cancer EBRT) received (125)I brachytherapy after attempted placement of 10cc of a diluted hydrogel spacer between the prostate and rectum. RESULTS Spacing was achieved in 8 of the 11 (73%) patients but was not possible in 3 (1 prior brachytherapy and 2 prior EBRT) owing to fibrosis and adhesions. For the 8 patients in whom spacing was accomplished, the median space between the prostate and rectum was 10.9mm (prior EBRT) vs. 7.7mm (prior brachytherapy), p=0.048. Median followup was 15.7 months. One patient developed a prostato-rectal fistula requiring a diverting colostomy. The 16-month estimate of late Grade 3 or 4 gastrointestinal or genitourinary toxicity was 26%. One patient developed lymph node-positive recurrence. The 16-month prostate-specific antigen failure-free survival rate was 89%. Compared with baseline, Expanded Prostate Cancer Index Composite for Clinical Practice urinary quality of life (QoL) was significantly worse at 3 and 6 months but not significantly worse by 1 year. There were no significant changes throughout the study period in bowel or sexual QoL. CONCLUSION Hydrogel spacer placements may be feasible in most patients with prior pelvic radiation. Further followup is needed to determine whether spacer placement will produce long-term improvements in toxicity or QoL.

Impact of a Genomic Classifier of Metastatic Risk on Postprostatectomy Treatment Recommendations by Radiation Oncologists and Urologists

OBJECTIVE To evaluate how a genomic classifier (GC) that predicts the risk of metastasis after prostatectomy would impact adjuvant treatment recommendations made by radiation oncologists and urologists. The 2 specialties often disagree about postprostatectomy adjuvant treatment recommendations. MATERIALS AND METHODS Twenty-six radiation oncologists and 20 urologists with genitourinary oncology expertise reviewed de-identified clinical results from 11 patients after radical prostatectomy and made adjuvant treatment recommendations. The same cases were later randomized and reassigned, and treatment recommendations were made using the clinical information and GC test results together. RESULTS Using clinical information alone, observation was recommended in 42% of decisions made by urologists vs 23% by radiation oncologists (P < .0001). The GC test results altered 35% and 45% of treatment recommendations made by radiation oncologists and urologists, respectively. Multivariate analysis showed GC risk was the strongest factor influencing treatment recommendations by both specialties, with an adjusted odds ratio of 4.17 (95% confidence interval [CI], 2.26-7.70) and 6.51 (95% CI, 4.29-9.88) for radiation oncologists and urologists, respectively. GC results indicating high metastatic risk resulted in intensification of treatment, whereas low metastatic risk resulted in less aggressive recommendations. The GC results increased interdisciplinary agreement in treatment recommendations, as the odds of a recommendation for adjuvant treatment by urologists vs radiation oncologists increased from 0.27 (95% CI, 0.17-0.44) to 0.46 (95% CI, 0.29-0.75) after results of the GC test were available. CONCLUSION The GC test significantly influenced adjuvant postprostatectomy treatment recommendations, reduced disagreement between radiation oncologists and urologists, and has the potential to enhance personalization of postprostatectomy care.

Who Bears the Greatest Burden of Aggressive Treatment of Indolent Prostate Cancer

PURPOSE The long-term prostate cancer-specific survival for patients initially managed with active surveillance for low-risk prostate cancer ranges from 97% to 100%. We characterized factors that are associated with aggressive treatment with radical prostatectomy or radiation for indolent prostate cancer (defined as screening-detected, low-risk disease). METHODS The Surveillance, Epidemiology, and End Results Program was used to extract a cohort of 39,803 men diagnosed with prostate-specific antigen-detected, low-risk prostate cancer (clinical category T1c, Gleason score ≤6, and prostate-specific antigen <10) from 2004 to 2010. After socioeconomic profiles were generated from county-linked education and income data, multivariable logistic regression was used to determine whether there were any factors associated with high rates of aggressive treatment. RESULTS The rate of aggressive treatment among all men with indolent prostate cancer was 64.3%. Greater rates of aggressive treatment were experienced by men with high socioeconomic status, Caucasian men, and married men (P < .001 for all cases). The increased adjusted odds for receipt of aggressive therapy were 1.25 (95% confidence interval [CI], 1.17-1.32; P < .001), 1.26 (95% CI, 1.21-1.32; P < .001), and 1.88 (95% CI, 1.80-1.97; P < .001) for men with high socioeconomic status, Caucasian men, and married men, respectively, compared with men with low socioeconomic status, non-Caucasian men, and unmarried men, respectively. CONCLUSIONS Although men with high socioeconomic status, Caucasian men, and married men often receive the highest quality health care and have the best outcomes for many cancers, it seems that they are most at risk for the avoidable potential harms of aggressive treatment of indolent prostate cancer. Future policy should encourage more stringent guidelines for deferred treatment and culturally and sociodemographically competent counseling of active surveillance.

Racial disparities in an aging population: the relationship between age and race in the management of African American men with high-risk prostate cancer.

PURPOSE To evaluate the relationship between age and race on the receipt of definitive therapy among men with high-risk prostate cancer (CaP). METHODS We used the Surveillance, Epidemiology and End Results Program to identify 62,644 men with high-risk CaP (PSA >20 or Gleason 8-10 or stage ≥cT3a) diagnosed from 2004 to 2010. Multivariable logistic regression analysis modeled the interaction between age and race and its association with receipt of definitive therapy on 57,674 patients (47,879 white men; 9,795 African American [AA] men) with complete data on the covariates of interest. RESULTS Among men age ≥70, AA men had a higher risk of CaP-specific mortality (PCSM) compared to white men after adjusting for sociodemographic and prostate cancer-specific factors (Adjusted HR 1.20; 95% CI 1.02-1.38; P=0.02). Nevertheless, a significant interaction between race and age was found (Pinteraction=0.01), such that the adjusted odds of receiving definitive treatment for AA vs. white was 0.67 (95% CI 0.62-0.73; P<0.001) among men age <70, but was 0.60 (95% CI 0.55-0.66; P<0.001) among men age ≥70, suggesting increased racial disparity in the receipt of definitive treatment among older men. CONCLUSION AA men with high-risk CaP are less likely to receive definitive therapy than white men. This disparity is significantly larger among men age ≥70, despite excess PCSM among AA men in this group. With a rapidly expanding population of older minority men, this disparity should be urgently addressed to prevent increasing disparities in cancer care.

Weight Gain on Androgen Deprivation Therapy: Which Patients Are at Highest Risk?

OBJECTIVE To identify factors associated with weight gain at 1 year from initiation of androgen deprivation therapy (ADT). METHODS A retrospective review assessed weight change among 118 men with nonmetastatic prostate cancer treated with ADT for at least 6 months. Outcome associations were tested using 2-tailed t tests and linear regression. RESULTS Men in our cohort had significant weight gain (+1.32 kg, P=.0005) in the 1 year after ADT initiation. Three risk factors for weight gain on ADT were identified as follows: age<65 years (2.72 kg gained, P=.001), body mass index (BMI)<30 (1.98 kg gained, P=.00002), and nondiabetic status (1.56 kg gained, P=.0003). Multivariable regression found both age<65 years (beta=4.01, P=.02) and BMI<30 (beta=3.57, P=.03) to be independently predictive of weight gain, whereas nondiabetic status was nonsignificantly predictive of weight gain (beta=2.14, P=.29). Weight change was further stratified by the total number of risk factors present (risk score): scores of 0, 1, 2, and 3 risk factors corresponded to weight changes of -1.10, +0.41, +1.34, and +3.79 kg, respectively (P-trend=.0005). CONCLUSION Age<65 years and BMI<30 were both independently associated with weight gain 1 year after starting ADT. Increasing weight gain was also strongly associated with increasing number of baseline risk factors present. Despite traditional concerns about ADT in unhealthy men, these data suggest younger, healthier patients may be at higher risk for gaining weight on ADT and should be counseled accordingly.