Comparative effectiveness of radical prostatectomy with adjuvant radiotherapy versus radiotherapy plus androgen deprivation therapy for men with advanced prostate cancer.

BACKGROUND: Men with locally advanced prostate cancer (LAPCa) or regionally advanced prostate cancer (RAPCa) are at high risk for death from their disease. Clinical guidelines support multimodal approaches, which include radical prostatectomy (RP) followed by radiotherapy (XRT) and XRT plus androgen deprivation therapy (ADT). However, there are limited data comparing these substantially different treatment approaches. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, this study compared survival outcomes and adverse effects associated with RP plus XRT versus XRT plus ADT in these men. METHODS: SEER-Medicare data were queried for men with cT3-T4N0M0 (LAPCa) or cT3-T4N1M0 (RAPCa) prostate cancer. Propensity score methods were used to balance cohort characteristics between the treatment arms. Survival analyses were analyzed with the Kaplan-Meier method and Cox proportional hazards models. RESULTS: From 1992 to 2009, 13,856 men (≥65 years old) were diagnosed with LAPCa or RAPCa: 6.1% received RP plus XRT, and 23.6% received XRT plus ADT. At a median follow-up of 14.6 years, there were 2189 deaths in the cohort, of which 702 were secondary to prostate cancer. Regardless of the tumor stage or the Gleason score, the adjusted 10-year prostate cancer-specific survival and 10-year overall survival favored men who underwent RP plus XRT over men who underwent XRT plus ADT. However, RP plus XRT versus XRT plus ADT was associated with higher rates of erectile dysfunction (28% vs 20%; P = .0212) and urinary incontinence (49% vs 19%; P < .001). CONCLUSIONS: Men with LAPCa or RAPCa treated initially with RP plus XRT had a lower risk of prostate cancer-specific death and improved overall survival in comparison with those men treated with XRT plus ADT, but they experienced higher rates of erectile dysfunction and urinary incontinence.

Severe genitourinary toxicity following radiation therapy for prostate cancer--how long does it last?

PURPOSE: Radiation therapy is a common treatment for localized prostate cancer but long-term data are sparse on treatment related toxicity compared to observation. We evaluated the time course of grade 2-4 genitourinary toxicities in men treated with primary radiation or observation for T1-T2 prostate cancer. MATERIALS AND METHODS: We performed a population based cohort study using Medicare claims data linked to SEER (Surveillance, Epidemiology and End Results) data. Cumulative incidence functions for time to first genitourinary event were calculated based on the competing risks model with death before any genitourinary event as a competing event. The generalized estimating equation method was used to evaluate the risk ratios of recurrent events. RESULTS: Of the study patients 60,134 received radiation therapy and 25,904 underwent observation. The adjusted risk ratio for genitourinary toxicity was 2.49 (95% CI 2.00-3.11) for 10 years and thereafter. Patients who had required prior procedures for obstruction/stricture, including transurethral prostate resection, before radiation therapy were at significantly increased risk for genitourinary toxicity (risk ratio 2.78, 95% CI 2.56-2.94). CONCLUSIONS: This study demonstrates that the increased risk of grade 2-4 genitourinary toxicities attributable to radiation therapy persists 10 years after treatment and thereafter. Patients who required prior procedures for obstruction/stricture were at higher risk for genitourinary toxicity than those without these preexisting conditions.

Fracture after androgen deprivation therapy among men with a high baseline risk of skeletal complications.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Receipt of androgen deprivation therapy (ADT) has been associated with an increased risk of skeletal-associated complications, such as a decrease in bone mineral density and an increase in fracture risk. Many men with pre-existing health conditions receive ADT as their primary treatment because they are considered to be inappropriate candidates for attempted curative treatments. However, several chronic health conditions, such as diabetes, rheumatoid disease and chronic liver disease, are strong predictors for osteoporosis and fractures. We undertook the present study aiming to quantify the impact of treating men with ADT who carry known risk factors for skeletal complications. Among these high-risk men, more than 58% develop at least one fracture after ADT within the 12 years of follow-up. Men who sustained a fracture within 48 months experienced an almost 40% higher risk of mortality than those who did not. Our findings suggest that treating men with a high fracture risk at baseline with long-term ADT may have serious adverse consequences. OBJECTIVE: To quantify the impact of androgen deprivation therapy (ADT) in men with a high baseline risk of skeletal complications and evaluate the risk of mortality after a fracture. PATIENTS AND METHODS: We studied 75994 men, aged ≥ 66 years, with localized prostate cancer from the Surveillance, Epidemiology and End Results-Medicare linked data. Cox proportional hazard models were employed to evaluate the risk. RESULTS: Men with a high baseline risk of skeletal complications have a higher probability of receiving ADT than those with a low risk (52.1% vs 38.2%, P < 0.001). During the 12-year follow-up, more than 58% of men with a high risk and 38% of men with a low risk developed at least one fracture after ADT. The dose effect of ADT is stronger among men who received ADT only compared to those who received ADT with other treatments. In the high-risk group, the fracture rate increased by 19.9 per 1000 person-years (from 52.9 to 73.0 person-years) for men who did not receive ADT compared to those who received 18 or more doses of gonadotropin-releasing hormone agonist among men who received ADT only, and by 14.2 per 1000 person-years (from 45.2 to 59.4 person-years) among men who received ADT and other treatments. Men experiencing a fracture had a 1.38-fold higher overall mortality risk than those who did not (95% CI, 1.34-1.43). CONCLUSIONS: Men with a high baseline risk of skeletal complications developed more fractures after ADT. The mortality risk is 40% higher after experiencing a fracture. Consideration of patient risk before prescribing ADT for long-term use may reduce both fracture risk and fracture-associated mortality.

Review of Cardiovascular Risk of Androgen Deprivation Therapy and the Influence of Race in Men with Prostate Cancer.

Androgen deprivation therapy is the cornerstone of prostate cancer therapy. Recent studies have revealed an association between androgen deprivation therapy and cardiovascular adverse effects such as myocardial infarction and stroke. This review summarizes the available research on the cardiovascular risk of men using androgen deprivation therapy. We also discuss racial disparities surrounding both prostate cancer and cardiovascular disease, emphasizing the importance of biological/molecular and socioeconomic factors in assessing baseline risk in patients beginning androgen ablation. Based on the literature, we provide recommendations for monitoring patients who are at high risk for a cardiovascular adverse event while being treated on androgen deprivation therapy. This review aims to present the current research on androgen deprivation therapy and cardiovascular toxicity with an emphasis on racial disparities and provides a framework for clinicians to decrease the cardiovascular morbidity in men that are being treated with hormone therapy.

Longitudinal associations of blood markers of insulin and glucose metabolism and cancer mortality in the third National Health and Nutrition Examination Survey.

Insulin and glucose may influence cancer mortality via their proliferative and anti-apoptotic properties. Using longitudinal data from the nationally representative Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994), with an average follow-up of 8.5 years to death, we evaluated markers of glucose and insulin metabolism, with cancer mortality, ascertained using death certificates or the National Death Index. Plasma glucose, insulin, C-peptide, and lipid concentrations were measured. Anthropometrics, lifestyle, medical, and demographic information was obtained during in-person interviews. After adjusting for age, race, sex, smoking status, physical activity, and body mass index, for every 50 mg/dl increase in plasma glucose, there was a 22% increased risk of overall cancer mortality. Insulin resistance was associated with a 41% (95% confidence interval (CI) (1.07-1.87; p = 0.01) increased risk of overall cancer mortality. These associations were stronger after excluding lung cancer deaths for insulin-resistant individuals (HR: 1.67; 95% CI: 1.15-2.42; p = 0.01), specifically among those with lower levels of physical activity (HR: 2.06; 95% CI: 1.4-3.0; p = 0.0001). Similar associations were observed for other blood markers of glucose and insulin, albeit not statistically significant. In conclusion, hyperglycemia and insulin resistance may be 'high-risk' conditions for cancer mortality. Managing these conditions may be effective cancer control tools.

Outcomes of localized prostate cancer following conservative management.

CONTEXT: Most newly diagnosed prostate cancers are clinically localized, and major treatment options include surgery, radiation, or conservative management. Although conservative management can be a reasonable choice, there is little contemporary prostate-specific antigen (PSA)-era data on outcomes with this approach. OBJECTIVE: To evaluate the outcomes of clinically localized prostate cancer managed without initial attempted curative therapy in the PSA era. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study of men aged 65 years or older when they were diagnosed (1992-2002) with stage T1 or T2 prostate cancer and whose cases were managed without surgery or radiation for 6 months after diagnosis. Living in areas covered by the Surveillance, Epidemiology, and End Results (SEER) program, the men were followed up for a median of 8.3 years (through December 31, 2007). Competing risk analyses were performed to assess outcomes. MAIN OUTCOME MEASURES: Ten-year overall survival, cancer-specific survival, and major cancer related interventions. RESULTS: Among men who were a median age of 78 years at cancer diagnosis, 10-year prostate cancer-specific mortality was 8.3% (95% confidence interval [CI], 4.2%-12.8%) for men with well-differentiated tumors; 9.1% (95% CI, 8.3%-10.1%) for those with moderately differentiated tumors, and 25.6% (95% CI, 23.7%-28.3%) for those with poorly differentiated tumors. The corresponding 10-year risks of dying of competing causes were 59.8% (95% CI, 53.2%-67.8%), 57.2% (95% CI, 52.6%-63.9%), and 56.5% (95% CI, 53.6%-58.8%), respectively. Ten-year disease-specific mortality for men aged 66 to 74 years diagnosed with moderately differentiated disease was 60% to 74% lower than earlier studies: 6% (95% CI, 4%-8%) in the contemporary PSA era (1992-2002) compared with results of previous studies (15%-23%) in earlier eras (1949-1992). Improved survival was also observed in poorly differentiated disease. The use of chemotherapy (1.6%) or major interventions for spinal cord compression (0.9%) was uncommon. CONCLUSIONS: Results following conservative management of clinically localized prostate cancer diagnosed from 1992 through 2002 are better than outcomes among patients diagnosed in the 1970s and 1980s. This may be due, in part, to additional lead time, overdiagnosis related to PSA testing, grade migration, or advances in medical care.

Survival following primary androgen deprivation therapy among men with localized prostate cancer.

CONTEXT: Despite a lack of data, increasing numbers of patients are receiving primary androgen deprivation therapy (PADT) as an alternative to surgery, radiation, or conservative management for the treatment of localized prostate cancer. OBJECTIVE: To evaluate the association between PADT and survival in elderly men with localized prostate cancer. DESIGN, SETTING, AND PATIENTS: A population-based cohort study of 19,271 men aged 66 years or older receiving Medicare who did not receive definitive local therapy for clinical stage T1-T2 prostate cancer. These patients were diagnosed in 1992-2002 within predefined US geographical areas, with follow-up through December 31, 2006, for all-cause mortality and through December 31, 2004, for prostate cancer-specific mortality. Instrumental variable analysis was used to address potential biases associated with unmeasured confounding variables. MAIN OUTCOME MEASURES: Prostate cancer-specific survival and overall survival. RESULTS: Among patients with localized prostate cancer (median age, 77 years), 7867 (41%) received PADT, and 11,404 were treated with conservative management, not including PADT. During the follow-up period, there were 1560 prostate cancer deaths and 11,045 deaths from all causes. Primary androgen deprivation therapy was associated with lower 10-year prostate cancer-specific survival (80.1% vs 82.6%; hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.03-1.33) and no increase in 10-year overall survival (30.2% vs 30.3%; HR, 1.00; 95% CI, 0.96-1.05) compared with conservative management. However, in a prespecified subset analysis, PADT use in men with poorly differentiated cancer was associated with improved prostate cancer-specific survival (59.8% vs 54.3%; HR, 0.84; 95% CI, 0.70-1.00; P = .049) but not overall survival (17.3% vs 15.3%; HR, 0.92; 95% CI, 0.84-1.01). CONCLUSION: Primary androgen deprivation therapy is not associated with improved survival among the majority of elderly men with localized prostate cancer when compared with conservative management.

Does Certificate of Need Minimize Intensity Modulated Radiation Therapy Use in Patients with Low Risk Prostate Cancer?

PURPOSE: Certificate of Need (CON) laws are optional from state to state, and are meant to limit proliferation of certain unnecessary medical facilities. Theoretically, CON should limit the use of IMRT (intensity modulated radiation therapy) in the population who likely would benefit from it the least: older or debilitated men with low risk prostate cancer. We evaluated the effect of CON on IMRT use in these patients in a population-based cohort. METHODS AND MATERIALS: Using the Surveillance, Epidemiology and End Results (SEER) database linked with Medicare files, we identified male residents of SEER regions who were diagnosed in 2004-2009 with low- risk prostate cancer (T1, Gleason≤6, PSA<10) and were either ≥70 years old or ≥65 years old with Charlson comorbidity score ≥ 2. The endpoint was percentage of newly diagnosed patients who were treated with IMRT within 12 month of cancer diagnosis. Logistic regression was used to assess the impact of CON laws on IMRT use. RESULTS: Over 37% (4,491) of the patients came from states with radiation oncology CON laws, whereas 63% (7,572) came from non-CON states. IMRT was performed on 30% of CON patients versus 28% of non-CON patients. Logistic regression analysis revealed that IMRT was utilized more often in CON states than in non-CON states, odds ratio (OR) 1.13 (95% CI 1.04-1.23, p=0.006). CONCLUSIONS: CON laws do not effectively limit use of IMRT in older or debilitated patients with low risk prostate cancer.

Fifteen-year Outcomes Following Conservative Management Among Men Aged 65 Years or Older with Localized Prostate Cancer.

BACKGROUND: To understand the threat posed by localized prostate cancer and the potential impact of surgery or radiation, patients and healthcare providers require information on long-term outcomes following conservative management. OBJECTIVE: To describe 15-yr survival outcomes and cancer therapy utilization among men 65 years and older managed conservatively for newly diagnosed localized prostate cancer. DESIGN, SETTINGS, AND PARTICIPANTS: This is a population-based cohort study with participants living in predefined geographic areas covered by the Surveillance, Epidemiology, and End Results program. The study includes 31 137 Medicare patients aged ≥65 yr diagnosed with localized prostate cancer in 1992-2009 who initially received conservative management (no surgery, radiotherapy, cryotherapy, or androgen deprivation therapy [ADT]). All patients were followed until death or December 31, 2009 (for prostate cancer-specific mortality [PCSM]) and December 31, 2011 (for overall mortality). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Competing-risk analyses were used to examine PCSM, overall mortality, and utilization of cancer therapies. RESULTS AND LIMITATIONS: The 15-yr risk of PCSM for men aged 65-74 yr diagnosed with screening-detected prostate cancer was 5.7% (95% confidence interval [CI] 3.7-8.0%) for T1c Gleason 5-7 and 22% (95% CI 16-35%) for Gleason 8-10 disease. After 15 yr of follow-up, 24% (95% CI 21-27%) of men aged 65-74 yr with screening-detected Gleason 5-7 cancer received ADT. The corresponding result for men with Gleason 8-10 cancer was 38% (95% CI 32-44%). The major study limitations are the lack of data for men aged <65 yr and detailed clinical information associated with secondary cancer therapy. CONCLUSIONS: The 15-yr outcomes following conservative management of newly diagnosed Gleason 5-7 prostate cancer among men aged ≥65 yr are excellent. Men with Gleason 8-10 disease managed conservatively face a significant risk of PCSM. PATIENT SUMMARY: We examined the long-term survival outcomes for a large group of patients diagnosed with localized prostate cancer who did not have surgery, radiotherapy, cryotherapy, or androgen deprivation therapy in the first 6 mo after cancer diagnosis. We found that the 15-yr disease-specific survival is excellent for men diagnosed with Gleason 5-7 disease. The data support conservative management as a reasonable choice for elderly patients with low-grade localized prostate cancer.

Cancer-specific survival after metastasis following primary radical prostatectomy compared with radiation therapy in prostate cancer patients: results of a population-based, propensity score-matched analysis.

BACKGROUND: Data regarding the difference in the clinical course from metastasis to prostate cancer-specific mortality (PCSM) following radical prostatectomy (RP) compared with radiation therapy (RT) are lacking. OBJECTIVE: To examine the association between primary treatment modality and prostate cancer-specific survival (PCSS) after metastasis. DESIGN, SETTING, AND PARTICIPANTS: We used the Surveillance Epidemiology and End Results-Medicare linked database from 1994 to 2007 for patients diagnosed with localized prostate cancer (PCa). We used cancer stage and Gleason score to stratify patients into low and intermediate-high risks. INTERVENTION: Radical prostatectomy or radiation therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Our outcome is time from onset of metastases to PCSM. Propensity score matching and Cox regression were used to analyze the PCSM hazard for the RP group compared with the RT group. RESULTS AND LIMITATIONS: Our study consisted of 66,492 men diagnosed with PCa, 51,337 men receiving RT, and 15,155 men undergoing RP within 1 yr of cancer diagnosis. During the study period, 2802 men were diagnosed as having metastatic disease. A total of 916 men with metastases were included in the propensity-matched cohort; of these men, 186 died from PCa. During the follow-up, for the low-risk patients, the adjusted PCSS after metastasis was 86.2% and 79.3% in the RP and RT groups, respectively; for the intermediate-high-risk patients, the PCSS after metastasis was 76.3% and 63.3% in the RP and RT groups, respectively. The hazard ratios estimating the risk of PCSM between the RP and RT groups were 0.64 (95% confidence interval [CI], 0.36-1.16) and 0.55 (95% CI, 0.39-0.77) for the low- and intermediate-high-risk groups, respectively. Because of the nature of observational studies, the results may be affected by residual confounders and treatment indication. CONCLUSIONS: Following the development of metastases, men who received primary RP have a longer PCSS than men who received primary RT. Our results may have implications for the timing and nature of local PCa treatment.

Fifteen-year survival outcomes following primary androgen-deprivation therapy for localized prostate cancer.

IMPORTANCE: One in 6 American men will be diagnosed as having prostate cancer during their lifetime. Although there are no data to support the use of primary androgen-deprivation therapy (ADT) for early-stage prostate cancer, primary ADT has been widely used for localized prostate cancer, especially among older patients. OBJECTIVE: To determine the long-term survival impact of primary ADT in older men with localized (T1/T2) prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: This was a population-based cohort study of 66,717 Medicare patients 66 years or older diagnosed from 1992 through 2009 who received no definitive local therapy within 180 days of prostate cancer diagnosis. The study was conducted in predefined US geographical areas covered by the Surveillance, Epidemiology, and End Results (SEER) Program. Instrumental variable analysis was used to assess the impact of primary ADT and control for potential biases associated with unmeasured confounding variables. The instrumental variable comprised combined health services areas with various usage rates of primary ADT. The analysis compared survival outcomes in the top tertile areas with those in the bottom tertile areas. MAIN OUTCOMES AND MEASURES: Prostate cancer-specific survival and overall survival. RESULTS: With a median follow-up of 110 months, primary ADT was not associated with improved 15-year overall or prostate cancer-specific survival following the diagnosis of localized prostate cancer. Among patients with moderately differentiated cancers, the 15-year overall survival was 20.0% in areas with high primary ADT use vs 20.8% in areas with low use (difference: 95% CI, -2.2% to 0.4%), and the 15-year prostate cancer survival was 90.6% in both high- and low-use areas (difference: 95% CI, -1.1% to 1.2%). Among patients with poorly differentiated cancers, the 15-year cancer-specific survival was 78.6% in high-use areas vs 78.5%, in low-use areas (difference: 95% CI, -1.8% to 2.4%), and the 15-year overall survival was 8.6% in high-use areas vs 9.2% in low-use areas (difference: 95% CI, -1.5% to 0.4%). CONCLUSIONS AND RELEVANCE: Primary ADT is not associated with improved long-term overall or disease-specific survival for men with localized prostate cancer. Primary ADT should be used only to palliate symptoms of disease or prevent imminent symptoms associated with disease progression.

Metabolic dysregulation of the insulin-glucose axis and risk of obesity-related cancers in the Framingham heart study-offspring cohort (1971-2008).

BACKGROUND: Obesity-related dysregulation of the insulin-glucose axis is hypothesized in carcinogenesis. We studied impaired fasting glucose (IFG) and other markers of insulin-glucose metabolism in the Framingham Heart Study-Offspring Cohort, which uniquely tracks these markers and cancer >37 years. METHODS: Participants were recruited between 1971 and 1975 and followed until 2008 (n = 4,615; mean age 66.8 years in 2008). Serum glucose, insulin, and hemoglobin A1c were determined from fasting blood in quart-annual exams. Lifestyle and demographic information was self-reported. HRs and 95% confidence intervals (CI) of cancer risk were computed using time-dependent survival analysis (SASv9.3), while accounting for temporal changes for relevant variables. RESULTS: We identified 787 obesity-related cancers, including 136 colorectal, 217 breast, and 219 prostate cancers. Absence versus presence of IFG 10 to 20 years and 20+ years before the event or last follow-up was associated with 44% (95% CI, 1.15-1.79) and 57% (95% CI, 1.17-2.11) increased risk of obesity-related cancers, respectively. When time-dependent variables were used, after adjusting for age, sex, smoking, alcohol, and body mass index, IFG was associated with a 27% increased risk of obesity-related cancer (HR = 1.27; CI, 1.1-1.5). Associations were stronger in smokers (HR = 1.41; CI, 1.13-1.76). Increased risk was noted among persons with higher insulin (HR = 1.47; CI, 1.15-1.88) and hemoglobin A1c (HR = 1.54; CI, 1.13-2.10) for the highest (≥ 5.73%) versus lowest (≤ 5.25%) category. A >2-fold increase in colorectal cancer risk was observed for all blood biomarkers of insulin-glucose metabolism, particularly with earlier IFG exposure. Nonsignificant increased risk of breast and prostate cancer was observed for blood biomarkers. CONCLUSIONS: Earlier IFG exposure (>10 years before) increased obesity-related cancer risk, particularly for colorectal cancer. IMPACT: Our study explicitly recognizes the importance of prolonged IFG exposure in identifying links between glucose dysregulation and obesity-related cancers.

Authentication of Algorithm to Detect Metastases in Men with Prostate Cancer Using ICD-9 Codes.

BACKGROUND: Metastasis is a crucial endpoint for patients with prostate cancer (PCa), but currently lacks a validated claims-based algorithm for detection. OBJECTIVE: To develop an algorithm using ICD-9 codes to facilitate accurate reporting of PCa metastases. METHODS: Medical records from 300 men hospitalized at Robert Wood Johnson University Hospital for PCa were reviewed. Using the presence of metastatic PCa on chart review as the gold standard, two algorithms to detect metastases were compared. Algorithm A used ICD-9 codes 198.5 (bone metastases), 197.0 (lung metastases), 197.7 (liver metastases), or 198.3 (brain and spinal cord metastases) to detect metastases, while algorithm B used only 198.5. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the two algorithms were determined. Kappa statistics were used to measure agreement rates between claim data and chart review. RESULTS: Algorithm A demonstrated a sensitivity, specificity, PPV, and NPV of 95%, 100%, 100%, and 98.7%, respectively. Corresponding numbers for algorithm B were 90%, 100%, 100%, and 97.5%, respectively. The agreement rate is 96.8% for algorithm A and 93.5% for algorithm B. CONCLUSIONS: Using ICD-9 codes 198.5, 197.0, 197.7, or 198.3 in detecting the presence of PCa metastases offers a high sensitivity, specificity, PPV, and NPV value.

Longitudinal associations of leisure-time physical activity and cancer mortality in the Third National Health and Nutrition Examination Survey (1986-2006).

Longitudinal associations between leisure-time physical activity (LTPA) and overall cancer mortality were evaluated within the Third National Health and Nutrition Examination Survey (NHANES III; 1988-2006; n = 15,535). Mortality status was ascertained using the National Death Index. Self-reported LTPA was divided into inactive, regular low-to-moderate and vigorous activity. A frequency-weighted metabolic equivalents (METS/week) variable was also computed. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated for overall cancer mortality in the whole sample, by body mass index categories and insulin resistance (IR) status. Nonsignificant protective associations were observed for regular low-to-moderate and vigorous activity, and for the highest quartile of METS/week (HRs range: 0.66-0.95). Individuals without IR engaging in regular vigorous activity had a 48% decreased risk of cancer mortality (HR: 0.52; 95% CI: 0.28-0.98) in multivariate analyses. Conversely, nonsignificant positive associations were observed in people with IR. In conclusion, regular vigorous activity may reduce risk of cancer mortality among persons with normal insulin-glucose metabolism in this national sample.

Does primary androgen-deprivation therapy delay the receipt of secondary cancer therapy for localized prostate cancer?

BACKGROUND: Despite evidence that shows no survival advantage, many older patients receive primary androgen-deprivation therapy (PADT) shortly after the diagnosis of localized prostate cancer (PCa). OBJECTIVE: This study evaluates whether the early use of PADT affects the subsequent receipt of additional palliative cancer treatments such as chemotherapy, palliative radiation therapy, or intervention for spinal cord compression or bladder outlet obstruction. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal population-based cohort study consists of Medicare patients aged ≥ 66 yr diagnosed with localized PCa from 1992 to 2006 in areas covered by the Surveillance Epidemiology and End Results (SEER) program. SEER-Medicare linked data through 2009 were used to identify the use of PADT and palliative cancer therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Instrumental variable analysis methods were used to minimize confounding effects. Confidence intervals were derived from the bootstrap estimates. RESULTS AND LIMITATIONS: This study includes 29 775 men who did not receive local therapy for T1-T2 PCa within the first year of cancer diagnosis. Among low-risk patients (Gleason score 2-7 in 1992-2002 and Gleason score 2-6 in 2003-2006) with a median age of 78 yr and a median follow-up of 10.3 yr, PADT was associated with a 25% higher use of chemotherapy (hazard ratio [HR]: 1.25; 95% confidence interval [CI], 1.08-1.44) and a borderline higher use of any palliative cancer treatment (HR: 1.07; 95% CI, 0.97-1.19) within 10 yr of diagnosis in regions with high PADT use compared with regions with low PADT use. Because this study was limited to men >65 yr, the results may not be applicable to younger patients. CONCLUSIONS: Early treatment of low-risk, localized PCa with PADT does not delay the receipt of subsequent palliative therapies and is associated with an increased use of chemotherapy.

Impact of comorbidity on survival among men with localized prostate cancer.

PURPOSE: To provide patients and clinicians more accurate estimates of comorbidity-specific survival stratified by patient age, tumor stage, and tumor grade. PATIENTS AND METHODS: We conducted a 10-year competing risk analysis of 19,639 men 66 years of age and older identified by the Surveillance, Epidemiology, and End Results (SEER) program linked to Medicare program files. All men were diagnosed with localized prostate cancer and received no surgery or radiation within 180 days of diagnosis. The analysis was stratified by tumor grade and stage and by age and comorbidity at diagnosis classified using the Charlson comorbidity index. Underlying causes of death were obtained from SEER. RESULTS: During the first 10 years after diagnosis, men with moderately and poorly differentiated prostate cancer were more likely to die from causes other than their disease. Depending on patient age, Gleason score, and number of comorbidities present at diagnosis, 5-year overall mortality rates for men with stage T1c disease ranged from 11.7% (95% CI, 10.2% to 13.1%) to 65.7% (95% CI, 55.9% to 70.1%), and prostate cancer-specific mortality rates ranged from 1.1% (95% CI, 0.0% to 2.7%) to 16.3% (95% CI, 13.8% to 19.4%). Ten-year overall mortality rates ranged from 28.8% (95% CI, 25.3% to 32.6%) to 94.3% (95% CI, 87.4% to 100%), and prostate cancer-specific mortality rates ranged from 2.0% (95% CI, 0.0% to 5.3%) to 27.5% (95% CI, 21.5% to 36.5%). CONCLUSION: Patients and clinicians should consider using comorbidity-specific data to estimate the threat posed by newly diagnosed localized prostate cancer and the threat posed by competing medical hazards.

Late gastrointestinal toxicities following radiation therapy for prostate cancer.

BACKGROUND: Radiation therapy is commonly used to treat localized prostate cancer; however, representative data regarding treatment-related toxicities compared with conservative management are sparse. OBJECTIVE: To evaluate gastrointestinal (GI) toxicities in men treated with either primary radiation or conservative management for T1-T2 prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: We performed a population-based cohort study, using Medicare claims data linked to the Surveillance Epidemiology and End Results data. Competing risk models were used to evaluate the risks. MEASUREMENTS: GI toxicities requiring interventional procedures occurring at least 6 mo after cancer diagnosis. RESULTS AND LIMITATIONS: Among 41,737 patients in this study, 28,088 patients received radiation therapy. The most common GI toxicity was GI bleeding or ulceration. GI toxicity rates were 9.3 per 1000 person-years after three-dimensional conformal radiotherapy, 8.9 per 1000 person-years after intensity-modulated radiotherapy, 5.3 per 1000 person-years after brachytherapy alone, 20.1 per 1000 person-years after proton therapy, and 2.1 per 1000 person-years for conservative management patients. Radiation therapy is the most significant factor associated with an increased risk of GI toxicities (hazard ratio [HR]: 4.74; 95% confidence interval [CI], 3.97-5.66). Even after 5 yr, the radiation group continued to experience significantly higher rates of new GI toxicities than the conservative management group (HR: 3.01; 95% CI, 2.06-4.39). Because our cohort of patients were between 66 and 85 yr of age, these results may not be applicable to younger patients. CONCLUSIONS: Patients treated with radiation therapy are more likely to have procedural interventions for GI toxicities than patients with conservative management, and the elevated risk persists beyond 5 yr.

Patterns and correlates of prostate cancer treatment in older men.

BACKGROUND: Although elderly men, particularly patients with low-risk prostate cancer and a life expectancy less than 10 years, are unlikely to benefit from prostate cancer active therapy, treatment rates in this group are high. METHODS: By using the population-based Surveillance, Epidemiology, and End Results program linked to Medicare data from 2004 to 2005, we examined the effects of clinical and nonclinical factors on the selection of prostate cancer active therapy (ie, radical prostatectomy, external beam radiation therapy, brachytherapy, or androgen deprivation therapy) in men aged≥75 years with a new diagnosis of localized prostate cancer. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for receiving prostate cancer active therapy. RESULTS: The majority of men aged≥75 years were treated with prostate cancer active therapy (81.7%), which varied by disease risk level: low, 72.2%; intermediate, 83.7%; and high, 86.4%. Overall, in older men, the percentage of the total variance in the use of prostate cancer active therapy attributable to clinical and nonclinical factors was minimal, 5.1% and 2.6%, respectively. In men with low-risk disease, comorbidity status did not affect treatment selection, such that patients with 1 or 2+ comorbidities were as likely to receive prostate cancer active therapy as healthy men: OR=0.98; 95% CI, 0.76-1.27 and OR=1.19; 95% CI, 0.84-1.68, respectively. Geographic location was the most powerful predictor of treatment selection (Northeast vs Greater California: OR=2.41; 95% CI, 1.75-3.32). CONCLUSION: Clinical factors play a limited role in treatment selection among elderly patients with localized prostate cancer.