Prostate cancer has a propensity to invade and grow along nerves, a phenomenon called perineural invasion (PNI). Recent studies suggest that the presence of PNI in prostate cancer has been associated ...with cancer aggressiveness.
We investigated the association between PNI and lethal prostate cancer in untreated and treated prostate cancer cohorts: the Swedish Watchful Waiting Cohort of 615 men who underwent watchful waiting, and the U.S. Health Professionals Follow-Up Study of 849 men treated with radical prostatectomy. One pathologist performed a standardized histopathologic review assessing PNI and Gleason grade. Patients were followed from diagnosis until metastasis or death.
The prevalence of PNI was 7% and 44% in the untreated and treated cohorts, respectively. PNI was more common in high Gleason grade tumors in both cohorts. PNI was associated with enhanced tumor angiogenesis, but not tumor proliferation or apoptosis. In the Swedish study, PNI was associated with lethal prostate cancer OR 7.4; 95% confidence interval (CI), 3.6-16.6;
< 0.001. A positive, although not statistically significant, association persisted after adjustment for age, Gleason grade, and tumor volume (OR 1.9; 95% CI, 0.8-5.1;
= 0.17). In the U.S. study, PNI predicted lethal prostate cancer independent of clinical factors (HR 1.8; 95% CI, 1.0, 3.3;
=0.04).
These data support the hypothesis that perineural invasion creates a microenvironment that promotes cancer aggressiveness.
Our findings suggest that PNI should be a standardized component of histopathologic review, and highlights a mechanism underlying prostate cancer metastasis.
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It is unknown whether alcohol intake is associated with the risk of lethal (metastatic or fatal) prostate cancer. We examine (1) whether alcohol intake among men at risk of prostate cancer is ...associated with diagnosis of lethal prostate cancer and (2) whether intake among men with nonmetastatic prostate cancer is associated with metastasis or death.
This prospective cohort study uses the Health Professionals Follow-Up Study (1986 to 2012). Our analysis of alcohol intake among men at risk of prostate cancer included 47,568 cancer-free men. Our analysis of alcohol intake among men with prostate cancer was restricted to 5,182 men diagnosed with nonmetastatic prostate cancer during follow-up. We examine the association of total alcohol, red and white wine, beer, and liquor with lethal prostate cancer and death. Multivariate Cox proportional hazards regression estimated hazard ratios (HRs) and 95% CIs.
Alcohol drinkers had a lower risk of lethal prostate cancer (any
none: HR, 0.84 95% CI, 0.71 to 0.99) without a dose-response relationship. Total alcohol intake among patients with prostate cancer was not associated with progression to lethal prostate cancer (any
none: HR, 0.99 95% CI, 0.57 to 1.72), whereas moderate red wine intake was associated with a lower risk (any
none: HR, 0.50 95% CI, 0.29 to 0.86;
trend = .05). Compared with none, 15 to 30 g/d of total alcohol after prostate cancer diagnosis was associated with a lower risk of death (HR, 0.71 95% CI, 0.50 to 1.00), as was red wine (any
none: HR, 0.74 95% CI, 0.57 to 0.97;
trend = .007).
Cancer-free men who consumed alcohol had a slightly lower risk of lethal prostate cancer compared with abstainers. Among men with prostate cancer, red wine was associated with a lower risk of progression to lethal disease. These observed associations merit additional study but provide assurance that moderate alcohol consumption is safe for patients with prostate cancer.
Prostate cancer has the widest racial disparities of any cancer, and these disparities appear at every stage of the cancer continuum. This review focuses on the disparities in prostate cancer between ...Black and White men, spanning from prevention and screening to clinical outcomes. We conduct an expansive review of the literature on racial disparities in prostate cancer, interpret the findings, and discuss areas of unmet need in research. We provide an overview of epidemiologic concepts necessary to understanding the current state of prostate cancer disparities, discuss the complexities of studying race, and review potential drivers of disparities in incidence and mortality. We argue that the cause of this disparity is multifactorial and due to a combination of social and environmental factors. The path forward needs to focus on enrolling and retaining Black men in prostate cancer clinical trials and observational studies and identifying potential interventions to improve prevention and clinical outcomes in Black men.
Men at a high genetic risk adhering to a healthy lifestyle had a reduced risk of lethal prostate cancer compared with men at a high genetic risk not adhering to a healthy lifestyle. The genetic risk ...of prostate cancer may be modifiable.
Prostate cancer is the most heritable cancer. There is a need to identify possible modifiable factors for men at an increased risk of prostate cancer due to genetic factors.
To examine whether men at an increased genetic risk of prostate cancer can offset their risk of disease or disease progression by adhering to a healthy lifestyle.
We prospectively followed 12 411 genotyped men in the Health Professionals Follow-up Study (1993–2019) and the Physicians’ Health Study (1983–2010). Genetic risk of prostate cancer was quantified using a polygenic risk score (PRS). A healthy lifestyle was defined by healthy weight, vigorous physical activity, not smoking, and a healthy diet.
Overall and lethal prostate cancer events (metastatic disease/prostate cancer–specific death) were analyzed using time-to-event analyses estimating hazard ratios (HRs) and lifetime risks.
During 27 yr of follow-up, 3005 overall prostate cancer and 435 lethal prostate cancer events were observed. The PRS enabled risk stratification not only for overall prostate cancer, but also for lethal disease with a four-fold difference between men in the highest and lowest quartiles (HR, 4.32; 95% confidence interval CI, 3.16–5.89). Among men in the highest PRS quartile, adhering to a healthy lifestyle was associated with a decreased rate of lethal prostate cancer (HR, 0.55; 95% CI, 0.36–0.86) compared with having an unhealthy lifestyle, translating to a lifetime risk of 1.6% (95% CI, 0.8–3.1%) among the healthy and 5.3% (95% CI, 3.6–7.8%) among the unhealthy. Adhering to a healthy lifestyle was not associated with a decreased risk of overall prostate cancer.
Our findings suggest that a genetic predisposition for prostate cancer is not deterministic for a poor cancer outcome. Maintaining a healthy lifestyle may provide a way to offset the genetic risk of lethal prostate cancer.
This study examined whether the genetic risk of prostate cancer can be attenuated by a healthy lifestyle including a healthy weight, regular exercise, not smoking, and a healthy diet. We observed that adherence to a healthy lifestyle reduced the risk of metastatic disease and prostate cancer death among men at the highest genetic risk. We conclude that men at a high genetic risk of prostate cancer may benefit from adhering to a healthy lifestyle.
The prevention of lethal prostate cancer is a critical public health challenge that would improve health and reduce suffering from this disease. In this review, we discuss the evidence surrounding ...specific lifestyle and dietary factors in the prevention of lethal prostate cancer. We present a summary of evidence for the following selected behavioral risk factors: obesity and weight change, physical activity, smoking, antioxidant intake, vitamin D and calcium, and coffee intake.
Overexpression of prostate-specific membrane antigen (PSMA) in tumor tissue and serum has been linked to increased risk of biochemical recurrence in surgically treated prostate cancer patients, but ...none of the studies have assessed its association with disease-specific mortality.
We examined whether high PSMA protein expression in prostate tumor tissue was associated with lethal disease, and with tumor biomarkers of progression, among participants of two U.S.-based cohorts (n = 902, diagnosed 1983-2004). We used Cox proportional hazards regression to calculate multivariable HRs and 95% confidence intervals (CI) of lethal prostate cancer, defined as disease-specific death or development of distant metastases (n = 95). Partial Spearman rank correlation coefficients were used to correlate PSMA with tumor biomarkers.
During an average 13 years of follow-up, higher PSMA expression at prostatectomy was significantly associated with lethal prostate cancer (age-adjusted HRQuartile(Q)4vs.Q1 = 2.42; Ptrend < 0.01). This association was attenuated and nonsignificant (multivariable-adjusted HRQ4vs.Q1 = 1.01; Ptrend = 0.52) after further adjusting for Gleason score and prostate-specific antigen (PSA) at diagnosis. High PSMA expression was significantly (P < 0.05) correlated with higher Gleason score and PSA at diagnosis, increased tumor angiogenesis, lower vitamin D receptor and androgen receptor expression, and absence of ets-related gene (ERG) expression.
High tumor PSMA expression was not an independent predictor of lethal prostate cancer in the current study. PSMA expression likely captures, in part, malignant features of Gleason grade and tumor angiogenesis.
PSMA is not a strong candidate biomarker for predicting prostate cancer-specific mortality in surgically treated patients.
Laboratory evidence suggests that vitamin D might influence prostate cancer prognosis.
We examined the associations between prediagnostic plasma levels of 25(OH)vitamin D 25(OH)D and 1,25(OH)(2) ...vitamin D 1,25(OH)(2)D and mortality among 1822 participants of the Health Professionals Follow-up Study and Physicians' Health Study who were diagnosed with prostate cancer. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total mortality (n = 595) and lethal prostate cancer (death from prostate cancer or development of bone metastases; n = 202). In models adjusted for age at diagnosis, BMI, physical activity, and smoking, we observed a HR of 1.22 (95% CI: 0.97, 1.54) for total mortality, comparing men in the lowest to the highest quartile of 25(OH)D. There was no association between 1,25(OH)(2)D and total mortality. Men with the lowest 25(OH)D quartile were more likely to die of their cancer (HR: 1.59; 95% CI: 1.06, 2.39) compared to those in the highest quartile (P(trend) = 0.006). This association was largely explained by the association between low 25(OH)D levels and advanced cancer stage and higher Gleason score, suggesting that these variables may mediate the influence of 25(OH)D on prognosis. The association also tended to be stronger among patients with samples collected within five years of cancer diagnosis. 1,25(OH)(2)D levels were not associated with lethal prostate cancer.
Although potential bias of less advanced disease due to more screening activity among men with high 25(OH)D levels cannot be ruled out, higher prediagnostic plasma 25(OH)D might be associated with improved prostate cancer prognosis.
Use of androgen deprivation therapy may increase the risk of cognitive impairment in men with prostate cancer. We performed a systematic review of the risk of overall cognitive impairment as an ...outcome in men receiving androgen deprivation therapy for prostate cancer.
Studies were identified through PubMed®, MEDLINE®, PsycINFO®, Cochrane Library and Web of Knowledge/Science™. Articles were included if they 1) were published in English, 2) had subjects treated for prostate cancer with androgen deprivation therapy, 3) incorporated longitudinal comparisons and 4) used control groups. In addition, prospective studies were required to assess an established cognitive related end point using International Cognition and Cancer Task Force criteria defining impaired cognitive performance as scoring 1.5 or more standard deviations below published norms on 2 or more tests, or scoring 2.0 or more standard deviations below published norms on at least 1 test. The effect of androgen deprivation therapy on cognitive impairment was pooled using a random effects model.
Of 221 abstracts 26 were selected for full text review, and 2 prospective and 4 retrospective studies were analyzed. Androgen deprivation therapy was not associated with overall cognitive impairment when the prospective cohort studies were pooled (OR 1.57, 95% CI 0.50 to 4.92, p = 0.44) with significant heterogeneity between estimates (I2 = 83%). In retrospective data the relative risk of any cognitive impairment, including senile dementia and Alzheimer disease, was increased in men receiving androgen deprivation therapy, although the difference was not statistically significant (HR 1.28, 95% CI 0.93 to 1.76, p = 0.13) with moderate heterogeneity between estimates (I2 = 67%).
Analyses between overall cognitive impairment and use of androgen deprivation therapy defined according to International Cognition and Cancer Task Force criteria in a pooled analysis were inconclusive. In retrospective cohort studies the risk of overall cognitive impairment after androgen deprivation therapy was not significant. Better prospective studies need to be designed for the assessment of this end point.
More than one-third of the calories consumed by U.S. and European populations contain acrylamide, a substance classified as a “probable human carcinogen” based on laboratory data. Thus, it is a ...public health concern to evaluate whether intake of acrylamide at levels found in the food supply is an important cancer risk factor. Mean dietary intake of acrylamide in adults averages 0.5 µg/kg of body weight per day, whereas intake is higher among children. Several epidemiological studies examining the relationship between dietary intake of acrylamide and cancers of the colon, rectum, kidney, bladder, and breast have been undertaken. These studies found no association between intake of specific foods containing acrylamide and risk of these cancers. Moreover, there was no relationship between estimated acrylamide intake in the diet and cancer risk. Results of this research are compared with other epidemiological studies, and the findings are examined in the context of data from animal models. The importance of epidemiological studies to establish the public health risk associated with acrylamide in food is discussed, as are the limitations and future directions of such studies.
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