Prostate Cancer In Elderly Men Research Articles

The influence of genetic and environmental factors on the incidence of prostate cancer in men

Introduction The prostate gland is a small reproductive organ found in men. It consists of 3 zones: central, peripheral and transitional. The most common localization of prostate cancer in elderly men is the peripheral zone. Prostate cancer is one of the most common cancers in men. It ranks second in terms of incidence and fifth in terms of lethality among men worldwide. There are many factors that contribute to the development of prostate cancer in men. We can divide them into two large groups: genetic factors and environmental factors. These include, among others: older age, ethnicity / race, positive family history, genetic predisposition, type of diet, obesity, smoking or higher height. Each of the above factors has a different impact on the incidence of prostate cancer, which has been demonstrated on the basis of the results of numerous studies and will be summarized in the following review. Materiał and Methods This review was based on available data collected in the PubMed database, using the following keywords: „Prostate Cancer”, „Epidemiology of Prostate Cancer” and „Risk factors of Prostate Cancer”. Conclusions Prostate cancer is a serious problem affecting men all over the world. Every year we observe an increasing incidence of this disease, which makes prostate cancer one of the most common cancers affecting men. There are many factors affecting the occurrence of this cancer, but it is extremely difficult to study their exact impact on the development of prostate cancer. Therefore, new initiatives and research should be undertaken to broadly understand the etiology and risk factors of this cancer.

Geographic Density of Linear Accelerators and Receipt of Radiation Therapy for Prostate Cancer

Radiation therapy (RT) is one among several definitive treatments for patients with prostate cancer. Recent analyses have suggested distance from a radiation oncologist influences the likelihood that a patient is to receive RT for their prostate cancer. We aimed to assess if linear accelerator density within healthcare referral regions (HRRs) impacts practice patterns regarding the treatment of prostate cancer patients.Along with the American Society for Radiation Oncology (ASTRO), we identified, and quality checked the location of linear accelerators in the United States as of July 2020, derived from the International Atomic Energy Agency Directory of Radiotherapy Centers (DIRAC) database. The address to each practice was geocoded using the Google Maps API within QGIS 3.12. The number of linear accelerators was determined in each HRR as defined by the Dartmouth Atlas; HRRs represent "regional healthcare markets for tertiary medical care." In 2014, the Dartmouth Atlas published data regarding the management of prostate cancer by HRR based on Medicare data from 2007 - 2011. Linear regression tested the association of linear accelerator density with receipt of prostate cancer radiation therapy.We identified 3,521 linear accelerators in the United States serving a population (as of the most recent US Census in 2010) of 309 million people; this represents approximately 88,000 people per linear accelerator, or 11.4 linear accelerators per million people. Among the 306 HRRs, the mean density of linear accelerators is 11.7 per million (standard deviation 5.2); 5 HRRs do not have a linear accelerator. For 227 HRRs, data regarding the proportion of Medicare beneficiaries over the age of 75 with prostate cancer who received RT was available. For every 1 additional linear accelerator per million, an additional 2.1 prostate cancer patients per 1,000 received RT (95% CI: 0.08 - 4.2; P = 0.04). For 234 HRRs reporting the number of prostatectomies per 1,000 Medicare beneficiaries under 75 with prostate cancer, there was no relationship between prostatectomy rate and number of linear accelerators (P = 0.42).Increasing HRR linear accelerator density is associated with increasing rate of receipt of radiotherapy for prostate cancer in elderly men. These findings need to be explored across other disease sites and age ranges to ascertain the magnitude of this effect and optimize the distribution of linear accelerators to best ensure access to care across the geographic spectrum.

A novel screening strategy for clinically significant prostate cancer in elderly men over 75 years of age.

A standard modality for prostate cancer detection in men 75 years and older has not been established. A simple screening method for elderly patients is needed to avoid unnecessary biopsies and to effectively diagnose prostate cancer. A retrospective study was conducted on elderly patients who had prostate biopsy at Kanazawa University Hospital (Kanazawa, Japan) between 2000 and 2017. Of the 2251 patients who underwent prostate biopsy, 254 had clinically significant prostate cancer (CSPC) with a Gleason score (GS) of ≥7 and 273 had a GS of <7 or no malignancy. In this study, patients aged 75 years or older were classified as elderly patients. GS ≥7 was characterized by a prostate-specific antigen (PSA) of the maximum area under the curve of 12 ng ml−1 with a sensitivity of 76.2% and a specificity of 73.2%. For PSA levels between 4 ng ml−1 and 12 ng ml−1, based on the maximum area under the curve, patients with three or four of the following factors may present a GS of ≥7: percent free PSA >24, PSA density ≥0.24 ng ml−2, positive findings on digital rectal examination, and transrectal with 90.0% sensitivity and 67.4% specificity. In this study, we found that raising the PSA cutoff to 12 ng ml−1 for CSPC in elderly individuals can significantly reduce unnecessary prostate biopsies. Furthermore, CSPC could be efficiently discovered by combining the four supplementary markers in patients with a PSA level of 4–12 ng ml−1. By performing this screening for elderly men over 75 years of age, unnecessary biopsies may be reduced and CSPC may be detected efficiently.

Predicting Prostate Cancer in Elderly Men

Predicting Prostate Cancer in Elderly Men

Re: Localised Prostate Cancer in Elderly Men Aged 80-89 Years, Findings from a Population-Based Registry.

Re: Localised Prostate Cancer in Elderly Men Aged 80-89 Years, Findings from a Population-Based Registry.

Epidemiological Determinants of Advanced Prostate Cancer in Elderly Men in the United States.

In this study, we examined the effects of individual-level and area-level characteristics on advanced prostate cancer diagnosis among Medicare eligible older men (ages 70+ years). We analyzed patients from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2000-2007) linked to US Census and County Business Patterns data. Cluster-adjusted logistic regression models were used to quantify the effects of individual preventive health behavior, clinical and demographic characteristics, area-level health services supply, and socioeconomic characteristics on stage at diagnosis. The fully adjusted model was used to estimate county-specific effects and predicted probabilities of advanced prostate cancer. In the adjusted analyses, low intensity of annual prostate-specific antigen (PSA) testing and other preventive health behavior, high comorbidity, African American race, and lower county socioeconomic and health services supply characteristics were statistically significantly associated with a higher likelihood of distant prostate cancer diagnosis. The fully adjusted predicted proportions of advanced prostate cancer diagnosis across 158 counties ranged from 3% to 15% (mean: 6%, SD: 7%). County-level socioeconomic and health services supply characteristics, individual-level preventive health behavior, demographic and clinical characteristics are determinants of advanced stage prostate cancer diagnosis among older Medicare beneficiaries; other health care-related factors such as family history, lifestyle choices, and health-seeking behavior should also be considered as explanatory factors.

Total Medicare Costs Associated With Diagnosis and Treatment of Prostate Cancer in Elderly Men

Localized prostate cancer diagnosis and treatment among elderly men who are not likely to benefit represents a potential source of low-value health care services. To quantify the costs to the Medicare program associated with detection and treatment of prostate cancer among elderly men in the United States. This nationwide, population-based, retrospective cohort study uses the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to identify men 70 years or older diagnosed with localized prostate cancer between 2004 and 2007 and to ascertain Medicare costs associated with diagnosis and workup, treatment, follow-up, and morbidity management of the disease. National Medicare costs were estimated using per-person costs, stage-adjusted prostate cancer incidence rates by age from SEER 2007 through 2011, and 2010 Census population estimates by age. Estimated costs to the Medicare program overall, and in each (mutually exclusive) category related to diagnosis and workup, treatment, follow-up, and morbidity management. This nationwide, population-based, retrospective cohort study included 49 692 men with nonmetastatic prostate cancer from the SEER-Medicare database (all participants were 70 years or older; 25 981 [52.3%] were 76 years or older). The median per-patient cost within 3 years after prostate cancer diagnosis was $14 453 (interquartile range [IQR], $4887-$27 899). The majority of this cost was attributable to treatment costs (median, $10 558; IQR, $1990-$23 718). Patients with a Gleason score of 6 or lower who pursued initial conservative management (no treatment within 12 months of diagnosis) had a 3-year median total cost of $1914 per patient. The estimated total 3-year cost to the Medicare program associated with the annual detection of prostate cancer in men 70 years or older is approximately $1.2 billion. Increasing active surveillance use in those with Gleason score of 6 or lower could reduce this cost by $320 million. There is substantial cost to the Medicare program associated with the diagnosis and treatment of localized prostate cancer among elderly men in the United States, despite the fact that these men are unlikely to die of prostate cancer. The majority of costs are related to treatment. Reducing provision of low-value health care services among this patient population could result in significant health care savings.

Human UDP-Glucuronosyltransferase 2B4 and 2B7 Are Responsible for Naftopidil Glucuronidation in Vitro.

Naftopidil (NAF) is widely used for the treatment of benign prostatic hyperplasia and prevention of prostate cancer in elderly men. These patients receive a combination of drugs, which involves high risk for drug–drug interaction. NAF exhibits superior efficacy but must be administered at a much higher dosage than other therapeutic drugs. We previously showed that extensive glucuronidation of NAF enantiomers caused poor bioavailability. However, the metabolic pathway and mechanism of action of NAF enantiomer remain to be elucidated. The present study was performed to identify the human UDP-glucuronosyltransferases (UGTs) responsible for the glucuronidation of NAF enantiomers and to investigate the potential inhibition of UGT activity by NAF. The major metabolic sites examined were liver and kidney, which were compared with intestine. Screening of 12 recombinant UGTs showed that UGT2B7 primarily contributed to the metabolism of both enantiomers. Moreover, enzyme kinetics for R(+)-NAF, UGT2B7 (mean Km, 21 μM; mean Vmax, 1043 pmol/min/mg) showed significantly higher activity than observed for UGT2B4 and UGT1A9. UGT2B4 (mean Km, 55 μM; mean Vmax, 1976 pmol/min/mg) and UGT2B7 (mean Km, 38 μM; mean Vmax, 1331 pmol/min/mg) showed significantly higher catalysis of glucuronidation of S(-)-NAF than UGT1A9. In human liver microsomes, R(+)-NAF and S(-)-NAF also inhibited UGT1A9: mean Ki values for R(+)-NAF and S(-)-NAF were 10.0 μM and 11.5 μM, respectively. These data indicate that UGT2B7 was the principal enzyme mediating glucuronidation of R(+)-NAF and S(-)-NAF. UGT2B4 plays the key role in the stereoselective metabolism of NAF enantiomers. R(+)-NAF and S(-)-NAF may inhibit UGT1A9. Understanding the metabolism of NAF enantiomers, especially their interactions with metabolic enzymes, will help to elucidate potential drug–drug interactions and to optimize the administration of this medicine.

Early Stage Cancer in Older Adults: Prostate—Avoiding Overtreatment and Undertreatment

The diagnosis of prostate cancer in elderly men is likely to increase over the next several decades, owing to changing demographics and a rising population of men older than 65 years. Given the heterogeneity and well-documented challenges in screening, diagnosing, and managing indolent versus aggressive prostate cancer, the geriatric patient population is particularly vulnerable to prostate cancer treatment nuances. Clinicians must become familiar with geriatric assessment tools to better answer life-expectancy questions prior to counseling patients on treatment options. The preferences and values of patients and their families must always be considered when making screening and treatment decisions. Careful selection of patients following a holistic evaluation will not only minimize overtreatment and undertreatment of prostate cancer, but may also allow for the early identification of unique geriatric vulnerabilities and permit quicker interventions to improve the quality of life of these men during their elderly years.

Early Stage Cancer in Older Adults: Prostate-Avoiding Overtreatment and Undertreatment.

The diagnosis of prostate cancer in elderly men is likely to increase over the next several decades, owing to changing demographics and a rising population of men older than 65 years. Given the heterogeneity and well-documented challenges in screening, diagnosing, and managing indolent versus aggressive prostate cancer, the geriatric patient population is particularly vulnerable to prostate cancer treatment nuances. Clinicians must become familiar with geriatric assessment tools to better answer life-expectancy questions prior to counseling patients on treatment options. The preferences and values of patients and their families must always be considered when making screening and treatment decisions. Careful selection of patients following a holistic evaluation will not only minimize overtreatment and undertreatment of prostate cancer, but may also allow for the early identification of unique geriatric vulnerabilities and permit quicker interventions to improve the quality of life of these men during their elderly years.

Use and Predictors of Expectant Management of Low and Intermediate Risk Localized Prostate Cancer in Elderly Men

IntroductionExpectant management reduces overtreatment in low risk but not intermediate risk localized prostate cancer. We assessed the use and predictors of expectant management to understand its uptake in practice in the United States. MethodsUsing the SEER (Surveillance, Epidemiology and End Results)-Medicare database, we conducted a retrospective cohort study of men 66 years or older diagnosed with low (25,506 patients) or intermediate risk (25,597) localized prostate cancer between 2004 and 2011 and followed through December 31, 2012. We defined expectant management as 1) no definitive therapy and at least 1 prostate specific antigen test or repeat biopsy 4 to 12 months after diagnosis or 2) receiving definitive therapy after prostate specific antigen testing or repeat biopsy 7 to 12 months after diagnosis. We performed separate analyses for low and intermediate risk groups using multiple logistic regressions. ResultsFor men diagnosed with prostate cancer in 2004 to 2011 expectant management increased from 22% to 43% in the low risk group and from 15% to 18% in the intermediate risk group. In the low risk group expectant management increased with age (adjusted OR 1.26 for age 71 to 75 years, 2.21 for 76 to 80 years, 6.33 for greater than 80 years; all p <0.0001 compared to age 66 to 70 years). Expectant management uptake was higher among men with comorbidities (OR 1.29) and those residing in the Pacific region (adjusted OR 0.56 compared to East Coast). ConclusionsIn United States practice utilization of expectant management has steadily increased in low risk prostate cancer and remained low in intermediate risk prostate cancer through time. While men with comorbidities or advanced age were more likely to undergo expectant management, its use varied substantially by geographic region. Our findings bring attention to the presence of multiple barriers to expectant management implementation.

Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy-naive metastatic castration-resistant prostate cancer: results from PREVAIL

Prostate cancer disproportionately affects older men. Because age affects treatment decisions, it is important to understand the efficacy and tolerability of therapies for advanced prostate cancer in elderly men. This analysis describes efficacy and safety outcomes in men aged ≥75 years who received enzalutamide, an androgen receptor inhibitor, in the phase III PREVAIL trial. PREVAIL was a randomised, double-blind, multinational study of oral enzalutamide 160 mg/day (N = 872) versus placebo (N = 845) in chemotherapy-naive men with metastatic castration-resistant prostate cancer. Overall survival (OS) and radiographic progression-free survival (rPFS) were coprimary end points. Subgroup analysis of men aged ≥75 years (elderly) and men aged <75 years was pre-specified for the coprimary end points and adverse events (AEs). Among 609 elderly patients (35%) who participated in PREVAIL, median treatment duration was 16.6 and 5.0 months in the enzalutamide and placebo arms, respectively. In the elderly subgroup, OS was greater with enzalutamide than with placebo [32.4 months (95% confidence interval (CI) 27.7-not yet reached] versus 25.1 months (95% CI 22.6-28.0); hazard ratio (HR) = 0.61 (95% CI 0.47-0.79); P = 0.0001], as was rPFS [not yet reached (95% CI 12.3-not yet reached) versus 3.7 months (95% CI 3.6-5.3); HR = 0.17 (95% CI 0.12-0.24); P < 0.0001]. Irrespective of treatment assignment, incidence of AEs was similar between the two age groups, except for an overall higher incidence of falls among elderly patients than younger patients [84/609 (13.8%) versus 62/1106 (5.6%)] and among elderly patients receiving enzalutamide than those receiving placebo [61/317 (19.2%) versus 23/292 (7.9%)]. Elderly men benefited from treatment with enzalutamide in terms of OS and rPFS. Enzalutamide was well tolerated in the elderly subgroup and those aged <75 years. Age and enzalutamide treatment were associated with a higher incidence of falls. NCT01212991, ClinicalTrials.gov.

Diagnosis and treatment of prostate cancer in elderly men

Diagnosis and treatment of prostate cancer in elderly men

Pharmacotherapeutic management of metastatic, castration-resistant prostate cancer in the elderly: focus on non-chemotherapy agents.

In the past 4years, five new agents have been approved for metastatic, castration-resistant prostate cancer. Four of them are non-chemotherapeutic and generally well tolerated. However, each has toxicities that can negatively impact patients, particularly the elderly. This review covers the epidemiology of prostate cancer in elderly men. It discusses the efficacy data for sipuleucel-T, abiraterone in chemotherapy-naïve patients, enzalutamide in chemotherapy-naïve patients and radium-223 and presents any additional studies done for those over 75years of age. Disease burden, such as the presence or absence of visceral disease, and comorbid conditions weigh into the selection of therapy and are discussed here. Drug-drug interactions between these agents and other drugs commonly used in the elderly population are also considered. The emerging therapies tasquinimod and ipilimumab are reviewed. With the arrival of so many agents for prostate cancer, selection of the most appropriate agent can be perplexing, particularly because these agents were tested against placebo, not one another. Furthermore, the study population differs significantly from those seen in clinical practice. This review addresses these issues.

Urinary Melatonin Levels, Sleep Disruption, and Risk of Prostate Cancer in Elderly Men

Melatonin has anticarcinogenic properties in experimental models. We undertook a case–cohort study of 928 Icelandic men without prostate cancer (PCa) nested within the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort to investigate the prospective association between first morning-void urinary 6-sulfatoxymelatonin (aMT6s) levels and the subsequent risk for PCa, under the hypothesis that men with lower aMT6s levels have an increased risk for advanced PCa. We used weighted Cox proportional hazards models to assess the association between first morning-void aMT6s levels and PCa risk, adjusting for potential confounders. A total of 111 men were diagnosed with incident PCa, including 24 with advanced disease. Men who reported sleep problems at baseline had lower morning aMT6s levels compared with those who reported no sleep problems. Men with morning aMT6s levels below the median had a fourfold statistically significant increased risk for advanced disease compared with men with levels above the median (hazard ratio: 4.04; 95% confidence interval, 1.26–12.98). These results require replication in larger prospective studies with longer follow-up. Patient summaryIn this report, we evaluated the prospective association between urinary aMT6s levels and risk of PCa in an Icelandic population. We found that lower levels of aMT6s were associated with an increased risk for advanced PCa.

Prostate cancer incidence in hypogonadal men on long-term treatment with testosterone undecanoate injections.

e16041 Background: Concerns regarding the safety of testosterone treatment, particularly regarding prostate cancer in elderly men, still hamper the use of testosterone in hypogonadal men. Methods: ...

Are Pathological and Oncological Outcomes of Elderly Men Treated with Radical Prostatectomy Worse than Those of Younger Men? Matched-pair Analysis Between Patients Aged &lt;70 and ≥70 Years

To compare oncological outcomes of patients aged ≥70 years treated with radical prostatectomy with those of a clinically matched younger cohort. Data from 1268 patients undergoing radical prostatectomy between 2000 and 2009 were retrospectively reviewed. Patients were classified according to age (<70 or ≥70 years) at the time of prostatectomy. After matching pre-operative factors (i.e. prostate specific antigen, positive biopsy cores, Gleason score, clinical stage and D'Amico risk group), 333 patients were chosen from each group. The percentage of pathological stage ≥T3 in those of age <70 and ≥70 years was 30.3 and 33.0%, respectively (P = 0.51). The percentage of pathological Gleason score ≤6, 7 and ≥8 was not significantly different between the two age groups (P = 0.08). The percentage of organ-confined disease in those of age <70 and ≥70 years was 69.4 and 67.0%, respectively (P = 0.56). With a median follow-up of 50 months, 5-year prostate specific antigen recurrence-free survival in those of age <70 and ≥70 years was 83.4 and 80.1%, respectively (log rank, P = 0.199). Five-year cancer-specific survival in those of age <70 and ≥70 years was 100 and 99.4%, respectively (log rank, P = 0.317). Five-year overall survival in those of age <70 and ≥70 years was 98.4 and 96.4%, respectively (log rank, P = 0.228). Pathological and oncological outcomes in elderly patients (age ≥70 years) treated with radical prostatectomy were not significantly different from those of younger patients (age <70 years). This information will help refine the indications for definitive treatment for localized prostate cancer in elderly men.

Long-term treatment with testosterone undecanoate injections and its effect of prostate cancer incidence in hypogonadal men.

119 Background: Concerns regarding the safety of testosterone treatment, particularly regarding prostate cancer in elderly men, still hamper the use of testosterone in hypogonadal men. Methods: Registry studies of 942 men with testosterone levels less than or equal to 12.1 nmol/L from three German centers. Patients received testosterone undecanoate for up to 16 years. Results: In cohort A (mean age: 57.70 ± 6.76 years; Bremerhaven), prostate-specific antigen (PSA) increased from 1.77±0.97 to 2.0±1.01 ng/ml (p=0.0021). Prostate volume increased from 28.34±10.79 to 30.72±14.28 ml (p&lt;0.0001). Five out of 300 patients were diagnosed with prostate cancer. The proportion was 1.7% with an incidence of 39.4 per 10,000 patient-years. In cohort B (mean age: 59.53 ± 8.35 years; Norderstedt), PSA increased from 0.86±0.57 to 1.38±0.49 ng/ml (p&lt;0.0001). Prostate volume increased from 27.9±8.15 to 36.98±7.22 ml (p&lt;0.0001). Six out of 261 patients were diagnosed with prostate cancer. The proportion was 2.3% with an incidence of 54.5 per 10,000 patient-years. One patient in cohort B was treated with external beam radiation, all other patients underwent radical prostatectomy. In cohort C (mean age: 42.6 ± 13.4 years; Muenster), PSA increased from 1.6±0.4 to 1.9±0.4 (p&lt;0.001). Prostate volume increased from 16.9±5.1 to 19.9±5.3 ml (p&lt;0.001). No patient was diagnosed with prostate cancer. Conclusions: The PLCO trial reported an incidence of 116 per 10,000 patient-years (Andriole, NEJM 360(13):1310-9), the ERSPC trial 96.6 (Schröder, NEJM 366(11):981-90). Although these screening trials cannot be directly compared to our registries of hypogonadal men receiving testosterone replacement therapy, the incidence of prostate cancer in our registry studies does not suggest an increased risk in hypogonadal men on long-term testosterone treatment.

Who’s too old to screen? Prostate cancer in elderly men

Who’s too old to screen? Prostate cancer in elderly men

Consumption of Fish Products across the Lifespan and Prostate Cancer Risk

ObjectiveTo examine whether fish and fish oil consumption across the lifespan is associated with a lower risk of prostate cancer.DesignThe study was nested among 2268 men aged 67–96 years in the AGES-Reykjavik cohort study. In 2002 to 2006, dietary habits were assessed, for early life, midlife and later life using a validated food frequency questionnaire. Participants were followed for prostate cancer diagnosis and mortality through 2009 via linkage to nationwide cancer- and mortality registers. Adjusting for potential confounders, we used regression models to estimate odds ratios (ORs) and hazard ratios (HRs) for prostate cancer according to fish and fish oil consumption.ResultsAmong the 2268 men, we ascertained 214 prevalent and 133 incident prostate cancer cases, of which 63 had advanced disease. High fish consumption in early- and midlife was not associated with overall or advanced prostate cancer. High intake of salted or smoked fish was associated with a 2-fold increased risk of advanced prostate cancer both in early life (95% CI: 1.08, 3.62) and in later life (95% CI: 1.04, 5.00). Men consuming fish oil in later life had a lower risk of advanced prostate cancer [HR (95%CI): 0.43 (0.19, 0.95)], no association was found for early life or midlife consumption.ConclusionsSalted or smoked fish may increase risk of advanced prostate cancer, whereas fish oil consumption may be protective against progression of prostate cancer in elderly men. In a setting with very high fish consumption, no association was found between overall fish consumption in early or midlife and prostate cancer risk.