Rates and predictors of colorectal cancer screening by race among motivated men participating in a Prostate Cancer Risk Assessment Program

BACKGROUND:

Screening by fecal occult blood test and lower endoscopy has lowered colorectal cancer (CRC) mortality, but compliance gaps persist. Of concern are possible disparities in uptake of CRC screening between white and African American men. The goal of this study was to assess for disparities in uptake of CRC screening among men participating in a high‐risk prostate cancer clinic. If present, such disparities could support hypotheses for further research examining racial differences in awareness and patient preferences in undergoing CRC screening.

METHODS:

Baseline data on a racially diverse cohort of men aged 50 to 69 years at increased risk of prostate cancer collected via the Prostate Cancer Risk Assessment Program at Fox Chase Cancer Center were analyzed. Predictors of uptake of CRC screening were assessed using multivariate logistic regression.

RESULTS:

Compared with whites, African American men had statistically significantly lower uptake of fecal occult blood testing (African American 49.0% vs white 60.7%, P = .035), lower endoscopy (African American 44.1% vs white 58.5%, P = .011), and any CRC screening (African American 66.2% vs white 76.3%, P = .053). Predictors of uptake of lower endoscopy among African American men included older age (odds ratio [OR], 3.61; 95% confidence interval [CI], 1.87‐6.97), family history of CRC (OR, 3.47; 95% CI, 1.30‐9.25), and insurance status (OR, 1.90; 95% CI, 1.04‐3.46).

CONCLUSIONS:

Despite awareness of cancer risk and motivation to seek prostate cancer screening through a specialized prostate cancer risk assessment program, evidence supporting compliance gaps with CRC screening among men was found. Tailored messages to younger African American men with and without a family history of CRC are needed. Cancer 2011;. © 2011 American Cancer Society.     

Causes of death in men undergoing androgen suppression therapy for newly diagnosed localized or recurrent prostate cancer

BACKGROUND.

The authors estimated and characterized mortality after androgen suppression therapy (AST) use in men with newly diagnosed localized and recurrent prostate cancer.

METHODS.

The study cohorts comprised 102 men who were randomized to radiation therapy (RT) and AST and 46 men who underwent salvage AST for recurrence from a randomized trial that compared external beam RT and 6 months of AST to RT. Cox regression multivariable analyses were performed to estimate the mortality hazard ratio (HR) in men with moderate to severe as compared with no or minimal comorbidity, adjusting for age and known prostate cancer prognostic factors.

RESULTS.

After a median follow‐up of 8.4 years (interquartile range: 7.2‐9.6 years), prostate cancer‐specific mortality (PCSM) comprised 13% and 75% of all mortality in men with newly diagnosed localized and recurrent prostate cancer, respectively. There was an increased risk of death in men with moderate to severe as compared with no or minimal comorbidity (adjusted HR [AHR], 11.5; 95% confidence interval [CI], 5.2‐25.6; P < .001) in men with newly diagnosed localized prostate cancer but not in men with recurrent prostate cancer (AHR, 2.5; 95% CI, 0.2‐37.8; P = .51).

CONCLUSIONS.

The ability to measure an increase in the risk of death in men with moderate to severe as compared with no or minimal comorbidity undergoing AST decreases as the risk of PCSM increases, which may explain the discordance in the literature regarding the risk of cardiovascular death and AST use. Cancer 2008. © 2008 American Cancer Society.     

Utilization and expense of adjuvant cancer therapies following radical prostatectomy

BACKGROUND:

We sought to identify the costs of adjuvant therapies following radical prostatectomy (RP) and factors associated with their receipt.

METHODS:

We used SEER‐Medicare data from 2004‐2006 to identify 4247 men who underwent RP, of whom 600 subsequently received adjuvant therapies. We used Cox regression to identify factors associated with receipt of adjuvant therapies. Health care expenditures within 12 months of diagnosis were compared for RP alone versus RP with adjuvant therapies.

RESULTS:

Biopsy Gleason score, prostate‐specific antigen, risk group, and SEER region were significantly associated with receipt of adjuvant treatments (all P<.001). Higher surgeon volume was associated with lower odds of receiving adjuvant therapies (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.46‐0.78 [P<.001]). Factors associated with increased receipt of adjuvant therapies were positive surgical margins (HR, 3.02; 95% CI, 2.55‐3.57 [P<.001]), high‐risk group versus low‐risk group (HR, 7.65; 95% CI, 5.64‐10.37 [P<.001]), lymph node–positive disease (HR, 5.36; 95% CI, 3.71‐7.75 [P<.001]), and treatment in Iowa (HR, 1.93; 95% CI, 1.12‐3.32 [P = .019]) and New Mexico/Georgia/Hawaii (HR, 1.92; 95% CI, 1.09‐3.39 [P = .025]) versus San Francisco SEER regions (baseline). Age, race, comorbidities, and surgical approach were not associated with use of adjuvant therapies. The median expenditures attributable to postprostatectomy hormonal therapy, radiation therapy, and radiation with hormonal therapy versus were $1361, $12,040, and $23,487.

CONCLUSIONS:

Men treated by high‐volume surgeons were less likely to receive adjuvant therapies. Regional variation and high‐risk disease characteristics were associated with increased receipt of adjuvant therapies, which increased health care expenditures by 2‐ to 3‐fold when radiotherapy was administered. Cancer 2011. © 2011 American Cancer Society.     

Prospective study on metabolic factors and risk of prostate cancer

BACKGROUND:

There are inconsistent data regarding the association between metabolic factors, separately and combined, and the risk of prostate cancer and death from prostate cancer.

METHODS:

In the Metabolic Syndrome and Cancer Project (Me‐Can), data on body mass index (BMI); blood pressure; and blood levels of glucose, cholesterol, and triglycerides were collected for 289,866 men. Cox proportional hazard models were used to calculate relative risks (RRs) by exposures in quintiles as well as for z scores (with a mean of 0 and a standard deviation of 1) together with a composite sum of scores to assess the combined effect of metabolic factors. RRs were corrected for random errors in measurement.

RESULTS:

During a mean follow‐up of 12 years, 6673 men were diagnosed with prostate cancer and 961 died of the disease. Men with high levels of glucose and triglycerides were found to have a decreased risk of prostate cancer: top versus bottom quintile of glucose: RR, 0.82 (95% confidence interval [95% CI], 0.62‐1.08; P value for trend = .03) and top versus bottom quintile of triglycerides: RR, 0.88 (95% CI, 0.74‐1.04; P value for trend = .001). High BMI, elevated blood pressure, and a high composite z score were found to be associated with an increased risk of death from prostate cancer: top versus bottom quintile of BMI: RR, 1.36 (95% CI, 1.08‐1.71); systolic blood pressure: RR, 1.62 (95% CI, 1.07‐2.45); and per 1‐unit increase of the composite z score: RR, 1.13 (95% CI, 1.03‐1.25).

CONCLUSIONS:

The authors found no evidence of an association between high levels of metabolic factors and the risk of prostate cancer, but high BMI, elevated blood pressure, and a composite score of all metabolic factors were associated with an increased risk of death from prostate cancer. Cancer 2012. © 2012 American Cancer Society.     

Biochemical recurrence after radical prostatectomy for prevalent versus incident cases of prostate cancer : implications for management

BACKGROUND.

Among screened populations, it is unknown whether men with prostate cancer (PC) diagnosed at the initial screening (prevalent cases) have a different outcome than men who are diagnosed at subsequent screenings (incident cases) after adjusting for known prognostic factors.

METHODS.

The current study cohort was comprised of 1923 men from a prospective PC screening study who underwent radical prostatectomy (RP) between September 19, 1989 and May 22, 2002. Cox regression multivariate analysis was used to determine whether having prevalent PC versus incident PC was associated with the time to prostate‐specific antigen (PSA) failure after RP after adjusting for PSA level, Gleason score, clinical tumor (T) classification, and year of RP.

RESULTS.

Men with prevalent PC had higher PSA levels (P < .001) and more advanced clinical T classification (P < .001) than men with incident PC. After a median follow‐up of 6.1 years, factors that were associated with a significantly shorter time to PSA failure after RP were prevalent PC (adjusted hazard ratio [AHR], 1.8; 95% confidence interval [95% CI], 1.3‐2.6; P = .0005), baseline PSA (AHR, 1.07; 95%CI, 1.04‐1.09; P < .001), Gleason 7 disease (AHR, 2.5; 95% CI, 1.9‐3.3; P < .001), Gleason 8 to 10 disease (AHR, 2.3; 95%CI, 1.5‐3.5; P < .001), and the year of RP (AHR, 0.92; 95%CI, 0.86‐0.97; P = .003). Men with prevalent PC also had worse outcomes after adjusting for their more advanced pathologic features.

CONCLUSIONS.

After adjusting for known prognostic factors, men with prevalent PC had a poorer outcome after RP than men with incident PC. The authors believe that this finding should be taken into consideration when weighing the risk of recurrence and treatment options for men who are diagnosed with PC on their initial screening. Cancer 2008. © 2008 American Cancer Society.     

Impact of postoperative prostate‐specific antigen disease recurrence and the use of salvage therapy on the risk of death

BACKGROUND:

This report evaluated whether biochemical recurrence (BCR) as a time‐dependent covariate (t) after radical prostatectomy (RP) for prostate cancer was associated with the risk of death and whether salvage therapy with radiotherapy (RT) and/or hormonal therapy (HT) can lessen this risk

METHODS:

This was a retrospective cohort study of 3071 men who underwent RP at Duke University between 1988 and 2008 and had complete follow‐up data. A Cox regression multivariable analysis was used to determine whether BCR (t) was associated with the risk of death in men after adjusting for age, prostatectomy findings, and the use of salvage RT and/or HT.

RESULTS:

After a median follow‐up of 7.4 years, 546 (17.8%) men experienced BCR and 454 (14.8%) died. The median follow‐up after prostate‐specific antigen (PSA) failure was 11.2 years (interquartile range, 5.8‐16.0 years). BCR (t) was associated with an increased risk of death (adjusted hazards ratio [AHR], 1.03; 95% confidence interval [95% CI], 1.004‐1.06 [P = .025]). In men who experienced BCR, a PSA doubling time <6 months was associated with an increased risk of death (AHR, 1.55; 95% CI, 1.15‐2.1 [P = .004]); whereas a decrease in the risk of death was observed in men who received RT (AHR, 0.58; 95% CI, 0.40‐0.58 [P = .002]) or HT (AHR, 0.56; 95% CI, 0.37‐0.84 [P = .005]) after BCR.

CONCLUSIONS:

The occurrence of BCR was found to increase the risk of death in men undergoing RP for prostate cancer, and this risk appeared to increase as the time to BCR shortened. However, the addition of RT and/or HT in men with BCR significantly lowered this risk. Cancer 2010. © 2010 American Cancer Society.     

The Clinical and Economic Impacts of Skeletal‐Related Events Among Medicare Enrollees With Prostate Cancer Metastatic to Bone

Background.

Approximately 40% of men diagnosed with metastatic prostate cancer experience one or more skeletal-related events (SREs), defined as a pathological fracture, spinal cord compression, or surgery or radiotherapy to the bone. Accurate assessment of their effect on survival, health care resource utilization (HCRU), and cost may elucidate the value of interventions to prevent SREs.

Materials and Methods.

Men older than age 65 years with prostate cancer and bone metastasis diagnosed between 2004 and 2009 were identified from linked Surveillance Epidemiology and End Results–Medicare records. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk for death associated with SREs were calculated by using Cox regression. HCRU and costs (in 2013 U.S. dollars) were evaluated in a propensity score-matched cohort by using Poisson regression and Kaplan-Meier sample average estimators, respectively.

Results.

Among 3,297 men with prostate cancer metastatic to bone, 40% experienced ≥1 SRE (median follow-up, 19 months). Compared with men who remained SRE-free, men with ≥1 SRE had a twofold higher risk for death (HR, 2.29; 95% CI, 2.09–2.51). Pathological fracture was associated with the highest risk for death (HR, 2.77; 95% CI, 2.38–3.23). Among men with ≥1 SRE, emergency department visits were twice as frequent (95% CI, 1.77–2.28) and hospitalizations were nearly four times as frequent (95% CI, 3.20–4.40). The attributable cost of ≥1 SRE was $21,191 (≥1 SRE: $72,454 [95% CI, $67,362–$76,958]; SRE-free: $51,263 [95% CI, $45,439–$56,100]).

Conclusion.

Among men with prostate cancer metastatic to bone, experiencing ≥1 SRE is associated with poorer survival, increased HCRU, and increased costs. These negative effects emphasize the importance of SRE prevention in this population.

Implications for Practice:

This study confirms the substantial adverse clinical and economic effects of skeletal-related events (SREs) in men with prostate cancer. Compared with men who have prostate cancer metastatic to the bones and no SREs, men with prostate cancer metastatic to the bones experiencing ≥1 SRE had a twofold increase in the risk for death, a twofold increase in the number of emergency department visits, and a fourfold increase in the number of hospitalizations; they also incurred an additional $21,000 in direct medical costs attributed to SREs. Strategies to prevent SREs are potentially of high value in this patient population.     

Age‐specific physical activity and prostate cancer risk among white men and black men

BACKGROUND:

The relation of physical activity across the lifespan to risk of prostate cancer has not been thoroughly investigated, particularly among black men. The authors investigated physical activity, including activity during different age periods and of various intensities, in relation to prostate cancer incidence among white men and black men.

METHODS:

In total, 160,006 white men and 3671 black men ages 51 years to 72 years who were enrolled in the National Institutes of Health‐AARP Diet and Health Study reported their time spent per week engaging in physical activity during ages 15 to 18 years, 19 years to 29 years, 35 years to 39 years, and during the past 10 years. Cox regression models were used to examine physical activity, categorized by intensity (moderate or vigorous, light, and total), in relation to prostate cancer risk.

RESULTS:

During 7 years of follow‐up, 9624 white men and 371 black men developed prostate cancer. Among white men, physical activity had no association with prostate cancer regardless of age period or activity intensity. Among black men, engaging in ≥4 hours of moderate/vigorous intensity physical activity versus infrequent activity during ages 19 years to 29 years was related to a 35% lower risk of prostate cancer (relative risk, 0.65; 95% confidence interval [95% CI], 0.43‐0.99 [P_trend = .01]). Frequent moderate/vigorous physical activity at ages 35 years to 39 years also potentially was related to reduced prostate cancer risk (relative risk, 0.59; 95% CI, 0.36‐0.96 [P_trend = .15]).

CONCLUSIONS:

Regular physical activity may reduce prostate cancer risk among black men, and activity during young adulthood may yield the greatest benefit. This novel finding needs confirmation in additional studies. Cancer 2009. Published 2009 by the American Cancer Society.     

Suicide in patients with pancreatic cancer

BACKGROUND:

Depression is highly prevalent in patients with pancreatic cancer and can result in fatal outcomes from suicides. The authors report suicide rates among patients with pancreatic cancer in the United States and identify factors associated with greater suicide rates.

METHODS:

The current study reviewed data in the SEER database for patients diagnosed with pancreatic adenocarcinoma from 1995‐2005. Logistic regression models were used to perform multivariate modeling for factors associated with suicide, while Kaplan‐Meier analysis was used to assess factors affecting survival.

RESULTS:

Among 36,221 patients followed for 22,145 person‐years, the suicide rate was 135.4 per 100,000 person‐years. The corresponding rate in the US population aged 65‐74 years was 12.5 per 100,000 person‐years, with a Standardized Mortality Ratio (SMR) of 10.8 (95% CI, 9.2‐12.7). Greater suicide rates were noted in males (Odds Ratio (OR) 13.5 [95% CI, 3.2‐56.9, P < .001]) and, among males, in patients undergoing an operative intervention (OR 2.5 [95% CI, 1.0‐6.5, P = .05]). Married men had a lesser risk of committing suicide (OR 0.3 [95% CI, 0.1‐0.6, P = .002]). Median survival among patients undergoing operative intervention was 2 months for those who committed suicide compared with 10 months for those who did not commit suicide.

CONCLUSIONS:

Male patients with pancreatic adenocarcinoma have a risk of suicide nearly 11 times that of the general population. Patients who undergo an operative intervention are more likely to commit suicide, generally in the early postoperative period. Cancer 2011. © 2010 American Cancer Society.     

Statin medication use and the risk of biochemical recurrence after radical prostatectomy

BACKGROUND:

Although controversial, evidence suggests statins may reduce the risk of advanced prostate cancer (PC), and recently statin use was associated with prostate‐specific antigen (PSA) reductions among men without PC. The authors sought to examine the association between statin use and PSA recurrence after radical prostatectomy (RP).

METHODS:

The authors examined 1319 men treated with RP from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. Time to PSA recurrence was compared between users and nonusers of statin at surgery using Cox proportional hazards models adjusted for multiple clinical and pathological features.

RESULTS:

In total, 236 (18%) men were taking statins at RP. Median follow‐up was 24 months for statin users and 38 for nonusers. Statin users were older (P < .001) and underwent RP more recently (P < .001). Statin users were diagnosed at lower clinical stages (P = .009) and with lower PSA levels (P = .04). However, statin users tended to have higher biopsy Gleason scores (P = .002). After adjusting for multiple clinical and pathological factors, statin use was associated with a 30% lower risk of PSA recurrence (hazard ratio “HR”, 0.70; 95% confidence interval “CI”, 0.50‐0.97; P = .03), which was dose dependent (relative to no statin use; dose equivalent<simvastatin 20 mg: HR, 1.08; 95% CI, 0.66‐1.73; P = .78; dose equivalent = simvastatin 20 mg: HR, 0.57; 95% CI, 0.32‐1.00; P = .05; dose equivalent>simvastatin 20 mg: HR, 0.50; 95% CI, 0.27‐0.93; P = .03).

CONCLUSIONS:

In this cohort of men undergoing RP, statin use was associated with a dose‐dependent reduction in the risk of biochemical recurrence. If confirmed in other studies, these findings suggest statins may slow PC progression after RP. Cancer 2010. © 2010 American Cancer Society.     

Incidence of pulmonary embolism in oncologic outpatients at a tertiary cancer center

BACKGROUND:

Incidence of pulmonary embolism (PE) for different cancer types in oncology outpatients is unknown. The purposes of the current study is to determine the incidence of PE in oncology outpatients and to investigate whether the incidence for PE is higher in certain cancers.

METHODS:

A cohort of oncology outpatients who had imaging studies at Dana‐Farber Cancer Institute, a tertiary outpatient cancer institute, from January 2004 through December 2009 was identified using research patient data registry. Radiology reports were reviewed to identify patients who developed PE. Incidences of PE in the total population and in each of 16 predefined cancer groups were calculated. Risk of PE for each cancer was compared using Fisher exact test.

RESULTS:

A total of 13,783 patients was identified, of which 395 (2.87%; 95% confidence interval [CI], 2.59‐3.16) developed PE. The incidence of PE was highest in the central nervous system ([CNS] 12.90%; 95% CI, 8.45‐18.59), hepatobiliary (6.85%; 95% CI, 3.33‐12.24), pancreatic (5.81%; 95% CI, 3.59‐8.84), and upper gastrointestinal (5.81%; 95% CI, 3.96‐8.20) malignancies. The risk of PE was significantly higher for CNS (P < .0001; odds ratio [OR], 5.28), pancreatic (P = .0027; OR, 2.15), upper gastrointestinal (P = .0002; OR, 2.18), and lung/pleural malignancies (P = .0028; OR, 1.45). There was significantly lower risk of PE for hematologic (incidence, 1.16%; 95% CI, 0.79‐1.64; P < .0001; OR, 0.35) and breast malignancies (incidence, 1.50%; 95% CI, 1.02‐2.11; P < .0001; OR, 0.47).

CONCLUSIONS:

The incidence of PE in oncology outpatients in a tertiary cancer center during a 6‐year period was 2.87%. CNS, pancreatic, upper gastrointestinal, and lung/pleural malignancies had a significantly higher risk for PE than other malignancies, whereas hematologic and breast malignancies had a significantly lower risk. Cancer 2011. © 2011 American Cancer Society.     

Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality

BACKGROUND.

Adiposity has been linked inconsistently with prostate cancer, and few studies have evaluated whether such associations vary by disease aggressiveness.

METHODS.

The authors prospectively examined body mass index (BMI) and adult weight change in relation to prostate cancer incidence and mortality in 287,760 men ages 50 years to 71 years at enrollment (1995–1996) in the National Institutes of Health‐AARP Diet and Health Study. At baseline, participants completed questionnaires regarding height, weight, and cancer screening practices, including digital rectal examinations and prostate‐specific antigen tests. Cox regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (95% CIs).

RESULTS.

In total, 9986 incident prostate cancers were identified during 5 years of follow‐up, and 173 prostate cancer deaths were ascertained during 6 years of follow‐up. In multivariate models, higher baseline BMI was associated with significantly reduced total prostate cancer incidence, largely because of the relationship with localized tumors (for men in the highest BMI category [≥40 kg/m²] vs men in the lowest BMI category [<25 kg/m²]: RR, 0.67; 95% CI, 0.50–0.89; P = .0006). Conversely, a significant elevation in prostate cancer mortality was observed at higher BMI levels (BMI <25 kg/m²: RR, 1.0 [referent group]; BMI 25–29.9 kg/m²: RR, 1.25; 95% CI, 0.87–1.80; BMI 30–34.9 kg/m²: RR, 1.46; 95% CI, 0.92–2.33; and BMI ≥35 kg/m²: RR, 2.12; 95% CI, 1.08–4.15; P = .02). Adult weight gain from age 18 years to baseline also was associated positively with fatal prostate cancer (P = .009), but not with incident disease.

CONCLUSIONS.

Although adiposity was not related positively to prostate cancer incidence, higher BMI and adult weight gain increased the risk of dying from prostate cancer. Cancer 2007. Published 2007 by the American Cancer Society.     

Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer

BACKGROUND.

It has been demonstrated that Agent Orange exposure increases the risk of developing several soft tissue malignancies. Federally funded studies, now nearly a decade old, indicated that there was only a weak association between exposure and the subsequent development of prostate cancer. Because Vietnam War veterans are now entering their 60s, the authors reexamined this association by measuring the relative risk of prostate cancer among a cohort of men who were stratified as either exposed or unexposed to Agent Orange between the years 1962 and 1971 and who were followed during the interval between 1998 and 2006.

METHODS.

All Vietnam War era veterans who receive their care in the Northern California Veteran Affairs Health System were stratified as either exposed (n = 6214) or unexposed (n = 6930) to Agent Orange. Strata‐specific incidence rates of prostate cancer (International Classification of Diseases, 9th Revision code 185.0) were calculated. Differences in patient and disease characteristics (age, race, smoking history, family history, body mass index, finasteride exposure, prebiopsy prostate‐specific antigen (PSA) level, clinical and pathologic stage, and Gleason score) were assessed with chi‐square tests, t tests, a Cox proportional hazards model, and multivariate logistic regression.

RESULTS.

Twice as many exposed men were identified with prostate cancer (239 vs 124 unexposed men, respectively; odds ratio [OR], 2.19; 95% confidence interval [95% CI], 1.75‐2.75). This increased risk also was observed in a Cox proportional hazards model from the time of exposure to diagnosis (hazards ratio [HR], 2.87; 95% CI, 2.31‐3.57). The mean time from exposure to diagnosis was 407 months. Agent Orange‐exposed men were diagnosed at a younger age (59.7 years; 95% CI, 58.9‐60.5 years) compared with unexposed men (62.2 years; 95% CI, 60.8‐63.6 years), had a 2‐fold increase in the proportion of Gleason scores 8 through 10 (21.8%; 95% CI, 16.5%‐27%) compared with unexposed men (10.5%; 95% CI, 5%‐15.9%), and were more likely to have metastatic disease at presentation than men who were not exposed (13.4%; 95% CI, 9%‐17.7%) than unexposed men (4%; 95% CI, 0.5%‐7.5%). In univariate analysis, distribution by race, smoking history, body mass index, finasteride exposure, clinical stage, and mean prebiopsy PSA were not statistically different. In a multivariate logistic regression model, Agent Orange was the most important predictor not only of developing prostate cancer but also of high‐grade and metastatic disease on presentation.

CONCLUSIONS.

Individuals who were exposed to Agent Orange had an increased incidence of prostate cancer; developed the disease at a younger age, and had a more aggressive variant than their unexposed counterparts. Consideration should be made to classify this group of individuals as ‘high risk,’ just like men of African‐American heritage and men with a family history of prostate cancer. Cancer 2008. © 2008 American Cancer Society.     

Association of Aurora-A (STK15) kinase polymorphisms with clinical outcome of esophageal cancer treated with preoperative chemoradiation

BACKGROUND:

Aurora‐A/STK15 is a serine/threonine kinase critical for regulated chromosome segregation and cytokinesis. We investigated the association between 2 nonsynonymous single nucleotide polymorphisms in the coding region of STK15, T91A (Phe31Ile) and G169A (Val57Ile), and clinical outcome of esophageal cancer treated with preoperative chemoradiation.

METHODS:

Genotypes at Phe31Ile and Val57Ile were assessed from peripheral blood lymphocytes of 190 esophageal cancer patients and were correlated to response to treatment, recurrence rate, risk of death, disease‐free survival (DFS) and median survival time (MTS).

RESULTS:

All patients had resectable esophageal or gastroesophageal junction cancer and received preoperative chemoradiation followed by esophagectomy. The heterozygous variant Phe31/Ile variant was significantly associated with tumor recurrence (odds ratio [OR] = 4.39; 95% confidence interval [CI], 2.12‐8.94; P < .001), shorter DFS (P = .0001), and shorter MTS (P = .012). For patients receiving cisplatin‐based therapy, only the variant Phe31/Ile had an adverse effect on response (OR = 2.8; 95% CI, 1.01‐5.17; P = .048) and MTS (P = .026). The variant 91A‐169G haplotype carried a significant risk for lack of complete response (OR = 2.54; 95% CI, 1.15‐5.54) and higher rate of recurrence (OR = 2.73; 95%CI, 1.00‐7.29). The presence of at least 1 variant allele at each locus further increased the risk of recurrence (adjusted OR = 6.21; 95% CI, 2.28‐17.11; P = <.001), and was associated significantly shorter DFS (P = .003).

CONCLUSIONS:

Our study shows that functional SNPs in the STK15 gene are associated with higher rate of recurrence, higher likelihood of chemoratiotherapy‐resistance, shorter DFS, and shorter MTS. Confirmation of our data and understanding the mechanisms through which STK15 functional SNPs mediate resistance to chemoradiotherapy are warranted. Cancer 2012. © 2011 American Cancer Society.     

Alcohol consumption,finasteride, and prostate cancer risk

BACKGROUND:

Current research is inconclusive regarding the relation between alcohol consumption and prostate cancer risk. In this study, the authors examined the associations of total alcohol, type of alcoholic beverage, and drinking pattern with the risk of total, low‐grade, and high‐grade prostate cancer.

METHODS:

Data for this study came from the 2129 participants in the Prostate Cancer Prevention Trial (PCPT) who had cancer detected during the 7‐year trial and 8791 men who were determined by biopsy to be free of cancer at the trial end. Poisson regression was used to calculate relative risks (RRs) and 95% confidence intervals (95% CIs) for associations of alcohol intake with prostate cancer risk.

RESULTS:

Associations of drinking with high‐grade disease did not differ by treatment arm. In combined arms, heavy alcohol consumption (≥50 g of alcohol daily) and regular heavy drinking (≥4 drinks daily on ≥5 days per week) were associated with increased risks of high‐grade prostate cancer (RR, 2.01 [95% CI, 1.33‐3.05] and 2.17 [95% CI, 1.42‐3.30], respectively); less heavy drinking was not associated with risk. Associations of drinking with low‐grade cancer differed by treatment arm. In the placebo arm, there was no association of drinking with risk of low‐grade cancer. In the finasteride arm, drinking ≥50 g of alcohol daily was associated with an increased risk of low‐grade disease (RR, 1.89; 95% CI, 1.39‐2.56); this finding was because of a 43% reduction in the risk of low‐grade cancer attributable to finasteride treatment in men who drank <50g of alcohol daily and the lack of an effect of finasteride in men who drank ≥50 g of alcohol daily (P_interaction = .03).

CONCLUSIONS:

Heavy, daily drinking increased the risk of high‐grade prostate cancer. Heavy drinking made finasteride ineffective for reducing prostate cancer risk. Cancer 2009. © 2009 American Cancer Society.     

Clinical outcomes of oncologic gastrointestinal resections in patients with cirrhosis

BACKGROUND:

Cirrhosis is a risk factor for postoperative morbidity and mortality after general surgical procedures. However, the impact of cirrhosis on outcomes of surgical resection for gastrointestinal (GI) malignancies has not been described. The authors' objective was to characterize early postoperative and transitional outcomes in cirrhotic patients undergoing GI cancer surgery.

METHODS:

Query of the National Inpatient Sample Database (2005‐2008) identified 106,729 patients who underwent resection for GI malignancy; 1479 (1.4%) had cirrhosis. The association of cirrhosis with postoperative outcomes was examined. The primary outcome measure was in‐hospital mortality. Secondary outcomes included length‐of‐stay (LOS) and discharge to long‐term care facility (LTCF).

RESULTS:

Cirrhotic patients had higher risk of in‐hospital mortality (8.9% vs 2.8%, P < .001), longer LOS (11.5 ± 0.26 vs 10.0 ± 0.03 days, P < .001), and higher rate of discharge to LTCF (19.0% vs 15.7%, P < .001). Mortality was highest in patients with moderate to severe liver dysfunction (21.5% vs 6.5%, P < .001). On multivariate analysis, cirrhosis was an independent predictor of in‐hospital mortality (odds ratio [OR], 3.0; 95% confidence interval [CI] 2.5‐3.7) and nonhome discharge (OR, 1.7; 95% CI, 1.4‐2.0). In cirrhotic patients, moderate to severe liver dysfunction was the only independent predictor of in‐hospital mortality (OR, 4.03; 95% CI, 2.7‐5.9), but did not predict discharge disposition.

CONCLUSIONS:

Resection of GI malignancy in cirrhotics is associated with poor early postoperative and transitional outcomes, with severity of liver disease being the primary determinant of postoperative mortality. These data suggest that GI cancer operations can be performed safely in well‐selected cirrhotic patients with mild liver dysfunction. Cancer 2012;3494–3500. © 2011 American Cancer Society.     

Microsatellite instability and DNA ploidy in colorectal cancer

BACKGROUND:

Appropriate stratification tools for targeted surveillance after resection for colorectal cancer (CRC) are lacking. The objective of the current study was to investigate the effect of microsatellite instability (MSI) and DNA ploidy on surveillance after surgery.

METHODS:

The authors evaluated 186 consecutive, population‐based patients with stage I through III CRC who underwent surgery with curative intent and who entered a systematic surveillance program. MSI was analyzed with polymerase chain reaction for 5 known quasimonomorphic markers (BAT‐26, BAT‐25, NR‐21, NR‐24, and NR‐27), and DNA ploidy was analyzed with automated cytometry. Recurrence, recurrence‐free survival (RFS), and disease‐specific survival (DSS) were evaluated by univariate and multivariate statistical tests.

RESULTS:

Patients with MSI (20%) were significantly younger than patients without MSI (median age, 61 years vs 67 years; P = .016). Proximal location (adjusted odds ratio [AOR], 5.4; 95% confidence interval [95% CI], 2.1‐14.1 [P = .001]), large tumor size (≥5 cm: AOR, 3.5; 95% CI, 1.3–9.6 [P = .015]), and poor tumor differentiation (AOR, 6.6; 95% CI, 2–21.8 [P = .002]) were associated with MSI. MSI conveyed an increased risk for locoregional recurrence (OR, 2.9; 95% CI, 1.2–7 [P = .016]), with a trend toward a shorter time to recurrence (P = .060). Neither MSI status nor DNA ploidy predicted distant metastasis, RFS, or DSS. Lymph node status was the best predictor of distant spread (AOR, 3.9; 95% CI, 2–7.9 [P < .001]) and DSS (hazard ratio, 4.9; 95% CI, 2.6–9 [P < .001]).

CONCLUSIONS:

Patients who had microsatellite instable tumors were at increased risk for locoregional recurrence, whereas lymph node status was the best predictor of distant metastasis. Clinical surveillance and choice of modality (ie, endoscopy vs radiologic imaging) may be improved when patients are stratified according to these cancer features. Cancer 2009. © 2009 American Cancer Society.     

Immunohistochemical markers associated with brain metastases in patients with nonsmall cell lung carcinoma

BACKGROUND.

To the authors' knowledge, there are no reliable markers able to identify patients with nonsmall cell lung cancer (NSCLC) that will develop metastases to the brain. The authors investigated associations between immunohistochemical markers and the development of brain metastases in patients with NSCLC.

METHODS.

This was a hospital‐based, case‐control study of patients who were newly diagnosed with NSCLC between 1989 and 2003, developed brain metastases, and had pathology material available from both the primary NSCLC and the brain metastases. These patients were compared with a control group of patients who had NSCLC and no evidence of brain metastases. NSCLC was examined for expression levels of Ki‐67, caspase‐3, vascular endothelial growth factor A (VEGF‐A), VEGF‐C, E‐cadherin, and epidermal growth factor receptor (EGFR) in 54 surgical pathology specimens using immunohistochemistry, and associations were evaluated between those markers and the development of brain metastases.

RESULTS.

Brain metastases developed after a median of 12.5 months (range, 1.7‐89.4 months) after the diagnosis of NSCLC. A significantly increased risk of developing brain metastases was associated with patients with NSCLC who had primary tumors with high Ki‐67 levels (adjusted odds ratio [OR] of 12.2; 95% confidence interval [95% CI], 2.4‐70.4 [P < .001]), low caspase‐3 expression (adjusted OR of 43; 95% CI, 5.3 to >100 [P < .001]), high VEGF‐C expression (adjusted OR of 14.6; 95% CI, 2.0 to >100 [P < .001]), and low E‐cadherin (adjusted OR of 3.6; 95% CI, 0.9‐16.4 [P = .05]). No significant risk was associated with VEGF‐A or EGFR expression. High Ki‐67 expression also was associated with a shorter overall survival (P = .04).

CONCLUSIONS.

The results of the current study indicated that patients with NSCLC who had high Ki‐67 expression, low caspase‐3 expression, high VEGF‐C expression, and low E‐cadherin expression in their tumors may benefit from close surveillance because they may have an increased risk of developing brain metastases. Cancer 2008. © 2008 American Cancer Society.     

Survival Outcomes of Radical Prostatectomy Versus Radiotherapy in Intermediate-Risk Prostate Cancer: A NCDB Study

Background

Studies of various prostate cancer patient cohorts found men receiving external-beam radiotherapy (EBRT) had higher mortality than men undergoing radical prostatectomy (RP). Conversely, a recent clinical trial showed no survival differences between treatment groups. We used the National Cancer Data Base (NCDB) to evaluate overall survival in intermediate-risk (T2b-T2c or Gleason 7 [grade group II or III] or prostate-specific antigen 10-20 ng/mL) prostate cancer patients undergoing EBRT with or without androgen deprivation therapy (ADT), RP, or no initial treatment.

Targeted and Systematic Prostate Biopsy in Biopsy-naive Men With Positive Multiparameter Magnetic Resonance Imaging Findings: A Meta-analysis

We assessed the difference in the detection rate of prostate cancer, specifically clinically significant prostate cancer, using targeted biopsy (TB), systematic biopsy (SB), and the combination of these 2 (CB) in biopsy-naive men with positive multiparameter magnetic resonance imaging results. We performed a literature review in September 2018 using PubMed and the Web of Science. Relevant studies acquired from specific articles’ references were also reviewed. Only those studies that had provided the detection rate of TB, SB, and CB in biopsy-naive men with positive multiparameter magnetic resonance imaging findings were included for a total of 11 studies with 2099 patients. The combined strategy was better than TB or SB alone, with an odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.30-1.67; P < .001) and 1.45 (95% CI, 1.28-1.65; P < .001), respectively, in the overall detection rate. Also, TB was not better than SB, with an OR of 0.99 (95% CI, 0.87-1.12; P = .825). For the clinically significant prostate cancer detection rate, CB was still better than TB or SB alone, with an OR of 1.25 (95% CI, 1.11-1.42; P < .001) and an OR of 1.23 (95% CI, 1.08-1.40; P = .002), respectively. Again, TB was not better than SB, with an OR of 0.98 (95% CI, 0.86-1.12; P = .768). In conclusion, CB resulted in a better detection rate than TB or SB alone for both the overall prostate cancer detection rate and the clinically significant prostate cancer detection rate.