Association of Low Socioeconomic Status With Adverse Prostate Cancer Pathology Among African American Men Who Underwent Radical Prostatectomy

BackgroundWe tested for associations between socioeconomic status (SES) and adverse prostate cancer pathology in a population of African American (AA) men treated with radical prostatectomy (RP).Patients and MethodsWe retrospectively reviewed data from 2 institutions for AA men who underwent RP between 2010 and 2015. Household incomes were estimated using census tract data, and patients were stratified into income groups relative to the study population median. Pathologic outcomes after RP were assessed, including the postsurgical Cancer of the Prostate Risk Assessment (CAPRA-S) score and a definition of adverse pathology (stage ≥ pT3, Gleason score ≥ 4+3, or positive lymph nodes), and compared between income groups.ResultsWe analyzed data of 347 AA men. Median household income was $37,954. Low-SES men had significantly higher prostate-specific antigen values (mean 10.2 vs. 7.3; P < .01) and CAPRA-S scores (mean 3.4 vs. 2.5; P < .01), more advanced pathologic stage (T3-T4 31.8% vs. 21.5%; P = .03), and higher rates of seminal vesicle invasion (17.3% vs. 8.2%; P < .01), positive surgical margins (35.3% vs. 22.1%; P < .01), and adverse pathology (41.4% vs. 30.1%; P = .03). Linear and logistic regression showed significant inverse associations of SES with CAPRA-S score (P < .01) and adverse pathology (P = .03).ConclusionIn a population of AA men who underwent RP, we observed an independent association of low SES with advanced stage or aggressive prostate cancer. By including only patients in a single racial demographic group, we eliminated the potential confounding effect of race on the association between SES and prostate cancer risk. These findings suggest that impoverished populations might benefit from more intensive screening and early, aggressive treatment of prostatic malignancies.     

Obesity as a predictor of adverse outcome across black and white race

BACKGROUND:

Across multiple studies, obesity has been associated with an increased risk of higher grade disease and prostate‐specific antigen (PSA) recurrence after radical prostatectomy (RP). Whether these associations vary by race is unknown. In the current study, the authors examined the association between obesity and outcome after RP stratified by race.

METHODS:

A retrospective analysis was performed on 1415 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) database who underwent RP between 1989 and 2008. The association between increased body mass index (BMI) and adverse pathology and biochemical recurrence was examined using multivariate logistic regression and Cox models, respectively. Data were examined stratified by race.

RESULTS:

After adjusting for preoperative clinical characteristics, higher BMI was associated with higher tumor grade (P = .008) and positive surgical margins (P < .001) in white men, and similar but statistically nonsignificant trends were observed in black men. No significant interaction was noted between race and BMI for associations with adverse pathology (P_interaction≥.12). After adjusting for preoperative clinical characteristics, higher BMI was associated with an increased risk of recurrence in both white men (P = .001) and black men (P = .03). After further adjusting for pathologic variables, higher BMI was associated with significantly increased risk of recurrence in white men (P = .002) and black men (P = .01). No significant interactions were observed between race and BMI for predicting biochemical progression adjusting either for preoperative factors (P_interaction = .35) or for preoperative and pathologic features (P_interaction = .47).

CONCLUSIONS:

Obesity was associated with a greater risk of recurrence among both black men and white men. Obesity did not appear to be more or less influential in 1 race than another but, rather, was identified as a risk factor for aggressive cancer regardless of race. Cancer 2009. © 2009 American Cancer Society.     

Effect of a minimum lymph node policy in radical cystectomy and pelvic lymphadenectomy on lymph node yields,lymph node positivity rates,lymph node density,and survivorship in patients with bladder cancer

BACKGROUND:

Extended pelvic lymphadenectomy (PLND) during radical cystectomy (RC) reportedly improves bladder cancer‐specific survival. Lymph node counts are often a proxy for the extensiveness of a dissection. In the current study, the impact of an institutional policy requiring a minimum number of lymph nodes was assessed.

METHODS:

Patients undergoing RC and PLND for invasive bladder cancer between March 2000 and February 2008 were retrospectively reviewed at the study institution. Beginning March 1, 2004, a policy was established that at least 16 lymph nodes had to be examined. Specimens with <16 lymph nodes were resubmitted (including any fat) to detect additional lymph nodes. Lymph node yields, lymph node positivity, lymph node density (LND), and survivorship before and after policy implementation were compared.

RESULTS:

A total of 147 patients underwent surgery 4 years before policy implementation and 202 underwent surgery 4 years after. The median number of lymph nodes increased from 15 to 20. Percentage of cases with ≥16 lymph nodes increased from 42.9% to 69.3% (P <.01). The lymph node positivity rates did not change significantly, but the proportion of patients with LND <20% increased from 43.9% to 65.5% (P = .04). Overall survival increased from 41.5% to 72.3% (P <.01). Univariate and multivariate regression demonstrated that policy implementation, and subsequent increase in median lymph node yield, decreased mortality risk by 30% (hazards ratio [HR], 0.70; P = .04) and 48% (HR, 0.52; P = .01), respectively.

CONCLUSIONS:

Thorough evaluation of PLND specimens obtained at RC can be influenced by an institutional policy mandating a minimum number of lymph nodes. This could lead to greater confidence in pathologic staging and reliability of LND as a predictor of prognosis. Survival can improve due to increased awareness to perform a more thorough PLND. Cancer 2010. © 2010 American Cancer Society.     

Impact of race on biochemical disease recurrence after prostate brachytherapy

BACKGROUND:

Understanding racial differences in disease presentation and response to therapy is necessary for the effective treatment and control of prostate cancer. In this study, the authors examined the influence of race on biochemical disease‐free survival (BDFS) among men who received prostate brachytherapy.

METHODS:

In total, 2301 men were identified who had a minimum follow‐up of 24 months and had received low‐dose‐rate brachytherapy for prostate cancer at the Mount Sinai Medical Center from June 1990 to October 2008. Patient factors, with specific emphasis on patient race, were analyzed with respect to freedom from biochemical failure (FFbF). Kaplan‐Meier analyses, life‐tables, and log‐rank tests were used to identify variables that were predictive of 10‐year FFbF.

RESULTS:

In this series, a total of 2268 patients included 81% Caucasians, 12% African Americans, 6% Hispanics, and 1% Asians. The 10‐year actuarial FFbF rate was 70% for AA men and 84% for all others (P = .002). Between Caucasian men and AA men, the 10‐year FFbF rate was 83% versus 70%, respectively (P = .001).There was no significant difference in 10‐year FFbF between Caucasian men and Hispanic men (83% vs 86%, respectively; P = .6). The 10‐year FFbF rate for Hispanic men and AA men was 86% versus 70%, respectively (P = .062). A greater percentage of AA men presented with higher prostate‐specific antigen levels (PSA) (>10 ng/mL; 44% vs 21%; P < .001) and, thus, with higher risk disease (24% vs 15%; P < .001) compared with Caucasian men. Among the men with low‐risk disease, the 10‐year FFbF rate was 90% for Caucasian men and 76% for AA men (P = .041). The 10‐year BDFS rate for patients who received brachytherapy alone was 86% for Caucasian men and 61% for AA men (P = .001); however, this difference was not observed when brachytherapy was combined with androgen‐deprivation therapy(ADT) with or without supplemental external‐beam radiotherapy (EBRT). Multivariate analysis revealed that PSA (P = .024), Gleason score (P < .001), the biologic effective dose (P < .001), EBRT (P = .002), ADT (P = .03), and AA race (P = .037) were significant predictors of 10‐year FFbF. No significant differences was observed in overall survival, cause‐specific survival, or distant metastasis‐free survival between racial groups.

CONCLUSIONS:

AA race appeared to be an independent negative predictor of BDFS after prostate brachytherapy, and this result may highlight the need for more aggressive therapy in this patient population. Cancer 2011;. © 2011 American Cancer Society.     

Racial Disparities in Prostate Cancer–Specific Mortality in Men With Low-Risk Prostate Cancer

BackgroundMen 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 MethodsThe 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.ResultsAfter 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.ConclusionAmong 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.     

Disparities in prostate cancer screening,diagnoses, management,and outcomes between Indigenous and non-Indigenous men in a universal health care system

Background

Indigenous Peoples have higher morbidity rates and lower life expectancies than non-Indigenous Canadians. Identification of disparities between Indigenous and non-Indigenous men regarding prostate cancer (PCa) screening, diagnoses, management, and outcomes was sought.

Methods

An observational cohort of men diagnosed with PCa between June 2014 and October 2022 was studied. Men were prospectively enrolled in the province-wide Alberta Prostate Cancer Research Initiative. The primary outcomes were tumor characteristics (stage, grade, and prostate-specific antigen [PSA]) at diagnosis. Secondary outcomes were PSA testing rates, time from diagnosis to treatment, treatment modality, and metastasis-free, cancer-specific, and overall survivals.

Results

Examination of 1,444,974 men for whom aggregate PSA testing data were available was performed. Men in Indigenous communities were less likely to have PSA testing performed than men outside of Indigenous communities (32 vs. 46 PSA tests per 100 men [aged 50–70 years] within 1 year; p < .001). Among 6049 men diagnosed with PCa, Indigenous men had higher risk disease characteristics: a higher proportion of Indigenous men had PSA ≥ 10 ng/mL (48% vs. 30%; p < .01), TNM stage ≥ T2 (65% vs. 47%; p < .01), and Gleason grade group ≥ 2 (79% vs. 64%; p < .01) compared to non-Indigenous men. With a median follow-up of 40 months (interquartile range, 25–65 months), Indigenous men were at higher risk of developing PCa metastases (hazard ratio, 2.3; 95% CI, 1.2–4.2; p < .01) than non-Indigenous men.

Conclusions

Despite receiving care in a universal health care system, Indigenous men were less likely to receive PSA testing and more likely to be diagnosed with aggressive tumors and develop PCa metastases than non-Indigenous men.     

Colorectal carcinoma: Analysis of management in two medical eras

Trends in presentation, diagnosis, management, and outcome were analyzed for 503 patients with colorectal cancer seen at the UCLA Medical Center between 1960 and 1970 (Group A; n = 210) and 1980 and 1985 (Group B; n = 293). Patients in the latter group exhibited a shift in site to the right side of the colon (18% in Group A vs. 31% in Group B; P < .01), an increase in the number of primary resections without colostomy (38% vs. 61%; P < .01), a lower overall complication rate (28% vs. 18%; P = .01), and a decline in 30-day mortality (6.2% vs. 2%; P = .01). Although little difference was seen in detection of asymptomatic tumors, earlier lesions were treated in the latter group, accounting for substantially reduced rate of recurrence (69% in Group A vs. 44% in Group B; P < .01). Future management should include an emphasis on earlier detection in order to continue the trend toward enhanced survival. © 1993 Wiley-Liss, Inc.     

Breast cancer in men in the United States

BACKGROUND:

Breast cancer in men is rare, so clinical trials are not practical. Recommendations suggest treating men who are diagnosed with breast cancer using the guidelines for postmenopausal women; however, to date, no population‐based studies have evaluated patterns of care.

METHODS:

To examine characteristics, treatment, and survival among men with newly diagnosed breast cancer, in 2003 and 2004, 512 men were identified from the Surveillance, Epidemiology and End Results Program. Data were reabstracted and therapy was verified through the patients' treating physicians.

RESULTS:

The majority of men (79%) were diagnosed through discovery of a breast lump or other signs/symptoms. Among men who had invasive disease, 86% underwent mastectomy, 37% received chemotherapy, and 58% received hormone therapy. In multivariate analysis, tumor size (P = .01) and positive lymph node status (P < .0001) were associated positively with the use of chemotherapy, whereas age group (P < .0001) and current unmarried status (P = .01) had negative associations. Among men who had invasive, estrogen receptor (ER)‐positive/borderline tumors, the use of tamoxifen or aromatase inhibitors (AIs) was associated with age group (P = .05). Among men who had invasive disease, cancer mortality was associated with tumor size (P < .0001). Among men with ER‐positive/borderline disease, increased cancer mortality was associated with tumor size (P < .0001), current unmarried status (P = .04), and decreased mortality with tamoxifen (P = .04).

CONCLUSIONS:

Tumor characteristics and marital status were the primary predictors of therapy and cancer mortality among men with breast cancer. Although AIs are not currently recommended, they are commonly prescribed. However, their use did not result in a decrease in cancer mortality. Research must examine the efficacy of AIs with and without gonadotropin‐releasing hormone analogues. Cancer 2010. © 2010 American Cancer Society.     

Risk of cancer in long-term levothyroxine users: Retrospective population-based study

Levothyroxine is a widely prescribed medication for the treatment of an underactive thyroid. The relationship between levothyroxine use and cancer risk is largely underdetermined. To investigate the magnitude of the possible association between levothyroxine use and cancer risk, this retrospective case-control study was conducted using Taiwan’s Health and Welfare Data Science Center database. Cases were defined as all patients who were aged ≥20 years and had a first-time diagnosis for cancer at any site for the period between 2001 and 2011. Multivariable conditional logistic regression models were used to calculate an adjusted odds ratio (AOR) to reduce potential confounding factors. A total of 601 733 cases and 2 406 932 controls were included in the current study. Levothyroxine users showed a 50% higher risk of cancer at any site (AOR: 1.50, 95% CI: 1.46-1.54; P < .0001) compared with non–users. Significant increased risks were also observed for brain cancer (AOR: 1.90, 95% CI: 1.48-2.44; P < .0001), skin cancer (AOR: 1.42, 95% CI: 1.17-1.72; P < .0001), pancreatic cancer (AOR: 1.27, 95% CI: 1.01-1.60; P = .03), and female breast cancer (AOR: 1.24, 95% CI: 1.15-1.33; P < .0001). Our study results showed that levothyroxine use was significantly associated with an increased risk of cancer, particularly brain, skin, pancreatic, and female breast cancers. Levothyroxine remains a highly effective therapy for hypothyroidism; therefore, physicians should carefully consider levothyroxine therapy and monitor patients’ condition to avoid negative outcomes. Additional studies are needed to confirm these findings and to evaluate the potential biological mechanisms.     

Body size across the life course and prostate cancer in the Health Professionals Follow‐up Study

Current evidence of an association between body size and prostate cancer is conflicting, possibly due to differential effects of body size across the lifespan and the heterogeneity of the disease. We therefore examined childhood and adult body size in relation to total incident prostate cancer and prognostic subtypes in a prospective cohort of 47,491 US men in the Health Professionals Follow‐up Study. We assessed adult height, body mass index (BMI) in early and middle‐to‐late adulthood, adult waist circumference, and body shape at age 10. With follow‐up from 1986 to 2010, we estimated the relative risk (RR) of prostate cancer using Cox proportional hazards models. We identified 6,183 incident cases. Tallness was associated with increased risk of advanced‐stage tumors, particularly fatal disease (RR = 1.66, 95% CI 1.23–2.23, highest vs. lowest quintile, p_trend < 0.001). High BMI at age 21 was inversely associated with total prostate cancer (RR = 0.89, 95% CI 0.80–0.98, BMI ≥26 vs. 20–21.9, p_trend = 0.01) and with fatal and advanced disease. The association for late adult BMI differed by age (p_interaction < 0.001); high BMI was inversely associated with total prostate cancer (RR = 0.64, 95% CI 0.51–0.78, BMI ≥30 vs. 21–22.9, p_trend<0.001) and with non‐advanced and less aggressive tumors among men ≤65 years, whereas no association was seen among men >65 years. Adult waist circumference was weakly inversely associated with less aggressive disease. Childhood obesity was unclearly related to risk. Our study confirms tall men to be at increased risk of fatal and advanced prostate cancer. The influence of adiposity varies by prognostic disease subtype and by age. The relationship between body size and prostate cancer is complex. Body size changes progressively throughout life and consequent effects on prostate cancer risk may be associated with related changes in hormonal and metabolic pathways. This large prospective study examined potential associations between the risk of various prostate cancer subtypes and multiple anthropometric measures at different ages in men. Tallness was confirmed to be associated with an elevated risk of advanced prostate cancer, particularly fatal disease. The extent to which body weight influenced risk varied according to factors such as age and disease subtype.     

Independent prognostic impact of CD15 on complete remission achievement in patients with acute myeloid leukemia

The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9‐81.2]) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6‐176.0), with 2‐year disease‐free survival rate of 45.1% (95% confidence interval 39.6‐50.6). The median overall survival was 14.4 months (range 0.3‐177.0), with 2‐year overall survival rate of 42.2% (95% confidence interval 37.5‐46.9). At univariate analysis for CR achievement, age < 60 years (P < .001), World Health Organization classification (P = .045), low‐risk karyotype (P < .001), no high‐risk karyotype (P = .006), positivity for AML‐ETO (P = .004)/CBFβ‐MYH11 (P = .003)/CD15 (P = .006)/CD11b (P = .013), negativity for FLT3‐ITD (P = .001), Hb > 8 g/dL (P = .020), and white blood cell < 50 × 10⁹/L (P = .034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (P = .002), age < 60 years (P = .008), white blood cell < 50 × 10⁹/L (P = .017), and low‐risk/no high‐risk karyotype (P = .026/P = .025) retained an independent prognostic role on CR achievement . The baseline assessment of CD15 positivity appears to have a role in the risk evaluation for CR achievement in AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biologic features already reported.     

Sex Disparities in Myelodysplastic Syndromes: Genotype,Phenotype, and Outcomes

Introduction/Background The impact of biological sex on the clinical phenotype, genotype, and outcomes among patients with MDS is not well characterized. Materials and Methods We retrospectively reviewed the clinical and genomic data from male and female patients included in our institutional MDS database at Moffitt Cancer Center. Results Among 4580 patients with MDS, 2922 (66%) were men and 1658 (34%) were women. Women were younger (mean age 66.5 vs. 69 years for men, P < .001) at diagnosis. There were more Hispanic/black women than men (9% vs. 5%, P =<.001). Women had lower hemoglobin and higher platelet counts than men. More women had del 5q/monosomy 5 abnormalities compared to men (P =<.001). Therapy related MDS were more common in women than men (25% vs.17%, P=<.001). On assessment of molecular profile, SRSF2, U2AF1, ASXL1, and RUNX1 mutations were more frequent in men. The median overall survival (mOS) was 37.5 months (mo) for females compared to 35 monthsfor males, (P = .002). The mOS was significantly prolonged for women in lower-risk MDS, but not in higher-risk MDS. Women were more likely to respond to immunosuppression with ATG/CSA than men (38% vs. 19%, P= 0.04).Conclusion Ongoing research is needed for understanding the impact of sex on phenotype, genotype, and outcomes in patients diagnosed with MDS.     

Occupational sitting time and subsequent risk of cancer: The Japan Public Health Center‐based Prospective Study

Although occupational sitting time has been associated with adverse health outcomes and mortality, the association with cancer incidence remains unknown. This study investigated the association between occupational sitting time and risk of total and site‐specific cancer in a Japanese population. We evaluated 33 307 participants aged 50‐79 years who responded to a questionnaire in 2000‐2003 in the Japan Public Health Center‐based Prospective Study and were followed until 2013. Participants were grouped by sitting time at work. Hazard ratio (HR) and 95% confidence interval (CI) of cancer incidence were calculated with adjustment for potential confounders including moderate‐to‐vigorous physical activity. During 10.2 years of follow‐up, 3807 newly diagnosed cases of cancer were identified. Occupational sitting time was marginally associated with total cancer, with multivariable HRs for the ≥7 h/d vs 1 to <3 h/d category of 1.12 (95% CI, 0.99‐1.26; P for trend = .071) in men, but not women. Among findings for cancers at specific sites, long occupational sitting time was associated with increased risk of pancreas cancer, with multivariable HRs for the ≥7 h/d vs 1 to <3 h/d category of 2.25 (95% CI, 1.17‐4.34; P for trend = .021) in men, and lung cancer, with multivariable HRs for the ≥7 h/d vs 1 to <3 h/d category of 2.80 (95% CI, 1.33‐5.90; P for trend = .013) in women. Extended sitting time at work was associated with an increased risk of pancreas cancer in men and lung cancer in women.     

A genetic variant in the promoter of CD46 is associated with the risk and prognosis of hepatocellular carcinoma

CD46 (also known as membrane cofactor protein), which is a member of the membrane-bound complement regulatory protein family, has been reported to cause cancer cells to escape complement-dependent cytotoxicity. However, the association between CD46 polymorphisms and the risk of hepatocellular carcinoma (HCC) has not been investigated. This two-stage association study was conducted to assess the relationship between the tagging single nucleotide polymorphisms (tagSNPs) of CD46 and HCC risk and prognosis. A series of functional analyses were performed to study the underlying mechanisms. Among the eight tagSNPs, rs2796267 (P = .003) and rs2796268 (P = .011) were found to modify HCC risk in the discovery set. Only rs2796267 (P < .0001) was confirmed to be associated with HCC susceptibility in the validation set. Compared with the wild-type AA genotype, the GG genotype significantly increased the HCC risk (adjusted odds ratio [OR] = 2.03; 95% confidence interval [CI], 1.34-3.08; P = .001). Moreover, subgroups analysis suggested a positive correlation among male and younger patients, especially among drinkers, smokers, and hepatitis B surface antigen-positive individuals. In functional analyses, we found that the rs2796267 G allele in the promoter region of CD46 could increase the expression of CD46 by affecting the binding affinity of STAT5a. Furthermore, Cox regression analysis revealed that the rs2796267 AG/GG genotype was significantly associated with worse prognosis of resected patients with HCC (hazard ratio = 2.27; 95% CI, 1.27-4.05; P = .006). These results suggest that the CD46 rs2796267 polymorphism may contribute to susceptibility and prognosis of HCC by altering promoter activity.     

Association between exercise and primary incidence of prostate cancer

BACKGROUND:

Exercise is a modifiable lifestyle risk factor associated with prostate cancer risk reduction. However, whether this association is different as a function of race is unclear. In the current study, the authors attempted to characterize the link between exercise and prostate cancer (CaP) in white and black American men.

METHODS:

Using a prospective design, 307 men (164 of whom were white and 143 of whom were black) who were undergoing prostate biopsy completed a self‐reported survey that assessed exercise behavior (metabolic equivalent [MET] hours per week). Crude and adjusted logistic regression analyses were used to estimate the risk of prostate cancer controlling for age, body mass index, digital rectal examination findings, previous biopsy, Charlson comorbidity score, and family history of CaP stratified by self‐reported race.

RESULTS:

There was no significant difference noted with regard to the amount of exercise between racial groups (P = .12). Higher amounts of MET hours per week were associated with a decreased risk of CaP for white men in both crude (P = .02) and adjusted (P = .04) regression models. Among whites, men who exercised ≥ 9 MET hours per week were less likely to have a positive biopsy result compared with men exercising < 9 MET hours per week (odds ratio, 0.47; 95% confidence interval, 0.22‐0.99 [P = .047]). There was no association noted between MET hours per week and risk of CaP among black men in both crude (P = .79) and adjusted (P = .76) regression models.

CONCLUSIONS:

In a prospective cohort of men undergoing biopsy, increased exercise, measured as MET hours per week, was found to be associated with CaP risk reduction among white but not black men. Investigating race‐specific mechanisms by which exercise modifies CaP risk and why these mechanisms disfavor black men in particular are warranted. Cancer 2013. © 2013 American Cancer Society.     

Mortality increases when radical cystectomy is delayed more than 12 weeks

BACKGROUND:

Single‐institution series have documented the adverse impact of a 12‐week delay between resection of muscle‐invasive bladder cancer and radical cystectomy. These data are derived from tertiary centers, in which referral populations may confound outcomes. The authors sought to examine the survival impact of a delay in radical cystectomy using nationally representative data.

METHODS:

From the linked Surveillance, Epidemiology, and End Results–Medicare dataset, the authors identified subjects with stage II transitional cell carcinoma (TCC) of the bladder who underwent radical cystectomy between 1992 and 2001. They examined delays of 8, 12, and 24 weeks and incorporated these delay cutoffs into multivariate Cox proportional hazards survival models. Covariates included age, race/ethnicity, marital status, Charlson comorbidity index, and cancer grade.

RESULTS:

The authors identified 441 subjects with stage II TCC who underwent cystectomy during the study period. Compared with immediate surgery (ie, within 4‐8 weeks of transurethral resection), longer time to cystectomy increased the risk of both disease‐specific and overall mortality (hazard ratio [HR], 2.0; P < .01 and HR, 1.6; P < .01, respectively, for those delayed 12‐24 weeks; HR, 2.0; P < .01 for disease‐specific and overall death among those delayed beyond 24 weeks 1 year after diagnosis). Covariates associated with overall mortality included older age (HR, 1.04; P < .01) and comorbidity (HR, 2.0 for Charlson ≥3 vs Charlson 0‐1; P < .01).

CONCLUSIONS:

Delay in definitive surgical treatment beyond 12 weeks conferred an increased risk of disease‐specific and all‐cause mortality among subjects with stage II bladder cancer. Cancer 2009. © 2009 American Cancer Society.     

Association between immune checkpoint inhibitor-induced myocarditis and concomitant use of thiazide diuretics

Although an association has been reported between diuretics and myocarditis, it is unclear whether the risk of immune checkpoint inhibitor (ICI)-induced myocarditis is affected by concomitant diuretics. Thus, the aim of this work was to evaluate the impact of concomitant diuretics on ICI-induced myocarditis. This cross-sectional study used disproportionality analysis and a pharmacovigilance database to assess the risk of myocarditis with various diuretics in patients receiving ICIs via the analysis of data entered into the VigiBase database through December 2022. Multiple logistic regression analysis was performed to identify risk factors for myocarditis in patients who received ICIs. A total of 90 611 patients who received ICIs, including 975 cases of myocarditis, were included as the eligible dataset. A disproportionality in myocarditis was observed for loop diuretic use (reporting odds ratio 1.47, 95% confidence interval [CI] 1.02-2.04, P = .03) and thiazide use (reporting odds ratio 1.76, 95% CI 1.20-2.50, P < .01) in patients who received ICIs. The results of the multiple logistic regression analysis showed that the use of thiazides (odds ratio 1.67, 95% CI 1.15-2.34, P < .01) was associated with an increased risk of myocarditis in patients who received ICIs. Our findings may help to predict the risk of myocarditis in patients receiving ICIs.     

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

PurposeTo evaluate the relationship between age and race on the receipt of definitive therapy among men with high-risk prostate cancer (CaP).MethodsWe 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.ResultsAmong 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 (P_interaction = 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.ConclusionAA 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.     

Glutathione S‐transferase Pi 1 is a valuable predictor for cancer drug resistance in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy. However, there are few useful markers for diagnosis and treatment. Glutathione S‐transferase Pi 1 (GSTP1) has been reported as a predictor of malignancy or anticancer drug resistance in some cancers. We investigated the association of GSTP1 expression with the malignancy or drug resistance in ESCC cell lines and clinical tissue samples. Proliferation and apoptosis assays regarding GSTP1 expression were examined in ESCC cell lines. Proliferation of GSTP1 knockdown cells was significantly decreased (P < .01), and the frequency of early apoptosis was increased (P < .05). Invasion capacity of GSTP1 knockdown cells was slightly decreased in transwell assay. These results suggest that GSTP1 plays an important role in malignant potential. To examine the effects of GSTP1 on drug resistance, chemosensitivity assay and apoptosis assay under cisplatin exposure were carried out. Viability of GSTP1 knockdown cells treated with cisplatin was lower than that of control cells (P < .01). Moreover, the frequency of early and late apoptosis in GSTP1 knockdown cells was markedly increased over that of control cells by cisplatin exposure (P < .01). In immunohistochemistry assay of resected tissue samples, GSTP1 expression was significantly associated with clinical downstaging (P = .04) in 72 ESCC patients with neoadjuvant chemotherapy. Furthermore, there was a significant association between GSTP1 expression in resected tissue and biopsy samples in 34 ESCC patients without neoadjuvant chemotherapy (P = .02). In summary, GSTP1 was related to malignant potential and may be a predictive marker of drug resistance in ESCC patients.     

The impact of clinical factors on the development of late radiation toxicity: results from the Medical Research Council RT01 trial (ISRCTN47772397)

Aims

A variety of dosimetric parameters have been shown to influence the incidence of late radiation toxicity. The effect of other treatment- and patient-related factors is less well established. The aim of this study was to elucidate the influence of such factors in the development of late symptoms after radical radiotherapy to the prostate.

Materials and methods

Patient- and treatment-related factors that are thought to influence the development of late toxicity were analysed in 788 patients who had received radical radiotherapy to the prostate in the Medical Research Council RT01 trial. Late toxicity data were recorded using the Radiation Therapy Oncology Group, Late Effects of Normal Tissues/Subjective, Objective, Management, Analytic, Royal Marsden Hospital and the University of California, Los Angeles, Prostate Cancer Index. Acute toxicity was measured using the Radiation Therapy Oncology Group grading system.

Results

On multivariate analysis, acute bowel toxicity was statistically significantly associated with increased proctitis (hazard ratio = 1.63, 95% confidence interval 1.18, 2.24; P = 0.003) and increased stool frequency (hazard ratio = 1.77, 95% confidence interval 1.27, 2.46; P = 0.001). Hypertension was strongly associated with a decreased risk of poor urinary stream (hazard ratio = 0.25, 95% confidence interval 0.09, 0.71; P = 0.009). There was an increased risk of rectal bleeding with increased age (hazard ratio = 1.04 per year of age, 95% confidence interval 1.01, 1.08; P = 0.009). As expected, a higher prescribed dose increased the risk of several late toxicity end points. Although acute bladder toxicity was associated with the presence of bladder symptoms at 5 years, the effect disappeared for all symptoms except increased urinary frequency and haematuria when a change in bladder function from baseline was calculated. Patients with any pretreatment bladder symptoms were more likely to report increased urinary frequency (hazard ratio = 2.09, 95% confidence interval 1.48, 2.95; P < 0.0005), increased urinary incontinence (hazard ratio = 4.22, 95% confidence interval 2.13, 8.35; P < 0.0005) and decreased stream (hazard ratio = 2.64, 95% confidence interval 1.62, 4.31; P < 0.0005), after treatment and before the most recent follow-up assessment.

Conclusions

In this study, increased acute gastrointestinal and bladder symptoms and prescribed dose were associated with increased late radiation toxicity. The presence of hypertension seemed to be protective for the development of late effects. Baseline symptoms should be taken into account when radiation toxicity is analysed.