An evaluation of bicalutamide in the treatment of prostate cancer

Although prostate cancer is traditionally considered a disease of old age, improved diagnostic techniques have resulted in early diagnosis, and many men are now treated while still physically and sexually active. Current therapies for prostate cancer often include medical or surgical castration, which cause adverse effects on physical and sexual function; therefore, greater attention has been focused on quality of life. The nonsteroidal antiandrogen bicalutamide is an effective agent with a favorable tolerability profile and, in some settings, represents an alternative to castration. Mature survival data reveal that bicalutamide monotherapy provides survival benefits for untreated locally advanced disease that do not differ significantly from those of castration and maintains better physical capacity and sexual interest. Recent data from a prospective randomized trial demonstrate that bicalutamide given as immediate therapy, either alone or as adjuvant to therapy of curative intent, significantly reduces the risk of objective disease progression in patients with localized or locally advanced prostate cancer. Antiandrogens are also used in combination with castration, a treatment known as combined androgen blockade (CAB), for advanced disease. A randomized trial demonstrated that CAB with bicalutamide is associated with similar survival outcome to CAB with flutamide and is better tolerated. Current evidence demonstrates that bicalutamide currently has a favorable risk-benefit ratio in several stages of prostate cancer and that the role of bicalutamide will be further defined by ongoing studies.     

Relation of family history of prostate cancer to perceived vulnerability and screening behavior

Men with a positive family history of prostate cancer are known to be at increased risk for the disease; however, relatively little is known about their risk perceptions or screening behavior. To address these issues, the current study examined the relationship of family history of prostate cancer to perceived vulnerability of developing prostate cancer and prostate cancer screening practices. Participants were 83 men with a positive family history of prostate cancer and 83 men with a negative family history of prostate cancer. As predicted, men with a positive family history reported greater (p< or =0.05) perceived vulnerability of developing prostate cancer and stronger intentions to undergo screening (p< or =0.05). They also reported greater past performance of prostate-specific antigen screening and were more likely to request information about prostate cancer (p< or =0.05). Additional analyses indicated that perceived vulnerability mediated the relation between family history and intentions to undergo prostate cancer screening. Findings confirm the increased likelihood of men with a positive family history to undergo prostate cancer screening and suggest that heightened concerns about developing the disease are an important motivating factor.     

New treatment developments applied to elderly patients with advanced prostate cancer

Prostate cancer is a common disease amongst elderly men. Compared with younger patients, men over the age of 75 are more likely to present with advanced disease and have a greater risk of death from prostate cancer despite higher death rates from competing causes. Treatment options for advanced prostate cancer have improved considerably in the last two years. The immunotherapy sipuleucel-T, the cytotoxic cabazitaxel, the androgen biosynthesis inhibitor abiraterone acetate, the radioisotope radium-223 and the antiandrogen enzalutamide have all been shown to improve survival in randomized phase III studies for patients with metastatic castration-resistant prostate cancer. This review will focus on the clinical data regarding new treatment developments specifically applied to elderly patients with advanced prostate cancer.     

Epidemiology of Prostate Cancer

Prostate cancer is the most common malignancy among males worldwide, and is the second leading causeof cancer death among men in United States. According to GLOBOCAN (2012), an estimated 1.1 million newcases and 307,000 deaths were reported in 2012. The reasons for the increase of this disease are not known, butincreasing life expectancy and modified diagnostic techniques have been suggested as causes. The establishedrisk factors for this disease are advancing age, race, positive family history of prostate cancer and western diet(use of fat items). Several other risk factors, such as obesity, physical activity, sexual activity, smoking andoccupation have been also associated with prostate cancer risk, but their roles in prostate cancer etiology remainuncertain. This mini-review aims to provide risk factors, disease knowledge, prevalence and awareness aboutprostate cancer.     

Risk factors for prostate cancer: A multifactorial case-control study

Prostate cancer is the third most commonly diagnosed cancer among Pakistani men. It is a multifactorial disease involving genetics together with environmental factors. Countries where men have greater dietary fat intake showed increased prostate cancer mortality rates. A population based case-control study was conducted to evaluate various prostate cancer risk factors. Study subjects were 896 prostate cancer cases (2010-2015) and 900 age matched controls. Odds ratio (OR) and 95% CI were used to estimate the association between different risk factors and prostate cancer. P values for different factors were computed by t-test, chi-square test, and Fisher exact test. Results showed significant association of increased age (OR = 10.6; CI: 7.92-14.31; P = 0.0001; Z = 15.7) and smoking (P = 0.05) with risk of disease. Consistent evidence suggested that fruits (P = 0.0001), vegetables (P = 0.0007), and diabetes mellitus (OR = 0.84; CI: 0.72-0.97; P = 0.02; Z = 2.28) were significantly associated with decreased prostate cancer risk. Comparison of education, marital status, occupation, intake of meat (<100 grams/week, 101-250 grams/week, >250 grams/week), number of cigarettes smoked per day, smoking duration, and family history of disease among cases and controls were not associated (P > 0.05) with risk of prostate cancer. Most of the prostate cancer patients were at stage IV with a Gleason score ranging from 7-9 and had undergone surgery. This epidemiological study illustrated that age and smoking were potential risk factors for prostate cancer in Pakistani men. Furthermore, phytonutrients can reduce its risk to a greater extent. Prospective studies with detailed analysis and greater sample size are required to explore more accurate findings.     

Neoadjuvant doxil chemotherapy prior to androgen ablation plus radiotherapy for high-risk localized prostate cancer: feasibility and toxicity

Patients with clinical T3 or T4 prostate cancer or with elevated serum prostate-specific antigen (PSA) levels greater than 40 ng/ml are at high risk of failure with primary treatment. Chemotherapy administered at the time of diagnosis may decrease the risk of recurrence. Patients with high risk localized prostate cancer were treated with two cycles of liposomal doxorubicin (Doxil) at 50 mg/m2 every 28 days. Patients were assessed for response by digital rectal examination (DRE), PSA, and endorectal magnetic resonance imaging (MRI) (erMRI). Patients were then treated with androgen ablative therapy and prostate radiotherapy. Seven patients were treated. Three patients had T3 disease, and 4 patients had T2b disease with either PSA greater than 40 ng/ml or erMRI evidence of seminal vesicle involvement or extracapsular disease. Median PSA was 29.4 ng/ml. None of the seven patients experienced a significant response, as measured by changes in DRE, PSA, or erMRI. Toxicity was significant, with 4 of 7 patients developing skin toxicity. All seven patients responded to androgen ablative therapy and prostate irradiation. Neoadjuvant liposomal doxorubicin demonstrates no apparent activity and significant toxicity. New strategies are needed to improve outcomes in high-risk prostate cancer.     

Testing a multigene signature of prostate cancer death in the Swedish Watchful Waiting Cohort.

Although prostate cancer is a leading cause of cancer death, most men die with and not from their disease, underscoring the urgency to distinguish potentially lethal from indolent prostate cancer. We tested the prognostic value of a previously identified multigene signature of prostate cancer progression to predict cancer-specific death. The Orebro Watchful Waiting Cohort included 172 men with localized prostate cancer of whom 40 died of prostate cancer. We quantified protein expression of the markers in tumor tissue by immunohistochemistry and stratified the cohort by quintiles according to risk classification. We accounted for clinical variables (age, Gleason, nuclear grade, and tumor volume) using Cox regression and calculated receiver operator curves to compare discriminatory ability. The hazard ratio of prostate cancer death increased with increasing risk classification by the multigene model, with a 16-fold greater risk comparing highest-risk versus lowest-risk strata, and predicted outcome independent of clinical factors (P = 0.002). The best discrimination came from combining information from the multigene markers and clinical data, which perfectly classified the lowest-risk stratum where no one developed lethal disease; using the two lowest-risk groups as reference, the hazard ratio (95% confidence interval) was 11.3 (4.0-32.8) for the highest-risk group and difference in mortality at 15 years was 60% (50-70%). The combined model provided greater discriminatory ability (area under the curve = 0.78) than the clinical model alone (area under the curve = 0.71; P = 0.04). Molecular tumor markers can add to clinical variables to help distinguish lethal and indolent prostate cancer and hold promise to guide treatment decisions.     

Demographics, family histories, and psychological characteristics of prostate carcinoma screening participants

BACKGROUND: The goals of this study were to 1) understand the reasons that men seek prostate carcinoma screening, in light of the ongoing medical controversy surrounding screening; and 2) assess the level of psychological distress and perceived risk among men seeking screening, and whether or not these variables were dependent on a man's family history of prostate carcinoma. METHODS: The subjects were 126 men (40% had a family history of prostate carcinoma) who participated in a free prostate carcinoma detection program. Questionnaires, which were completed prior to prostate carcinoma screening, included demographic and medical information, reasons for screening participation, general and cancer-related psychological distress, and perceived risk for prostate carcinoma. RESULTS: Among both family history groups, self-referral was the most common reason for attending the screening, compared with receiving a recommendation from a health professional or from a friend or family member. Men with a positive family history were not more distressed than those without a family history; but as the authors predicted, men with a positive family history of prostate carcinoma did report higher levels of perceived risk relative to those without a family history. In addition, an interaction revealed that psychological distress was greater among men with a family history only among those who also reported elevated perceived risk. CONCLUSIONS: Similar to other prostate carcinoma screening programs, men in the current sample largely elected to attend the screening on their own. Furthermore, although perceived risk was higher among men with a family history compared with those without a family history, psychological distress was greater among men with a family history only among those who also reported elevated perceived risk. Thus, among men with a family history of the disease, perceived risk may be a marker of elevated psychological distress. Screening programs should assess family history and perceived risk because of the potential psychological implications for screening participants.     

膀胱癌侵犯前列腺的相关因素研究

目的 探讨膀胱癌侵犯前列腺的相关因素,为保留患者前列腺的相关研究提供一些临床依据.方法回顾性分析135例膀胱癌患者的临床资料,采用Logistic逐步回归法分析膀胱癌侵犯前列腺的影响因素.结果135例患者中,14例(10.4%)患者出现膀胱癌侵犯前列腺.多因素分析结果显示,肿瘤部位、肿瘤直径、肿瘤与膀胱颈口距离、肿瘤分级是膀胱癌侵犯前列腺的独立影响因素.肿瘤位于膀胱三角区或颈部的患者发生膀胱癌侵犯前列腺的风险是非膀胱三角区或颈部患者的1.784倍;肿瘤直径每增大1 cm,患者出现膀胱癌侵犯前列腺的风险增大2.375倍;肿瘤与膀胱颈口距离每降低1 cm,患者出现膀胱癌侵犯前列腺的风险增大2.079倍;高级别肿瘤患者发生膀胱癌侵犯前列腺的风险是低级别肿瘤患者的1.684倍.结论 肿瘤位于膀胱三角区或颈部、肿瘤与膀胱颈口的距离较近、肿瘤高级别和肿瘤较大是膀胱癌患者前列腺受侵犯的高危因素,要重点加强对这类人群的观察,注意手术范围.     

IGF-1 and IGFBP-3: Risk of prostate cancer among men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

IGF-1 and IGFBP-3 may influence risk of prostate cancer through their roles in cellular growth, metabolism and apoptosis, however, epidemiologic results have been inconsistent. The role of obesity in prostate cancer risk is not clearly understood, but hyperinsulinemia-related increases in bioactive IGF-1 levels, associated with obesity, could be a component of the relationship between the IGF-axis and prostate cancer. We conducted a nested case-control study in the prospective Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to examine associations between IGF-1 and IGFBP-3 and risk of prostate cancer. A total of 727 incident prostate cancer cases and 887 matched controls were selected for this analysis. There was no clear overall association between IGF-1, IGFBP-3 and IGF-1:IGFBP-3 molar ratio (IGFmr) and prostate cancer risk, however, IGFmr was associated with risk in obese men (BMI > 30, p-trend = 0.04), with a greater than 2-fold increased risk in the highest IGFmr quartile (OR 2.34, 95% CI 1.10-5.01). Risk was specifically increased for aggressive disease in obese men (OR 2.80, 95% CI 1.11-7.08). In summary, our large prospective study showed no overall association between the insulin-like growth factor axis and prostate cancer risk, however, IGFmr was related to risk for aggressive prostate cancer in obese men.     

Biopsy sampling and histopathological markers for diagnosis of prostate cancer

Prostate cancer is one of the most common malignant tumors and a leading cause of cancer-related morbidity and mortality. Irrespective of the method that allows for risk stratification of prostate cancer suspects, diagnosis relies on tissue sampling through prostate biopsy and subsequent histopathological evaluation. This provides critical information about disease aggressiveness, which is required for adequate patient management. Prostate biopsy methods have significantly evolved over the years, including the definition of indications, sampling schemes and use of imaging techniques (ultrasound and MRI) that allow for more accurate tissue sampling. In response to the challenges emerging from more precise collection of minute prostate tissue samples for analysis, histopathological assessment should include not only the observation of routinely stained sections, but also, and increasingly so, a series of ancillary techniques, especially immunohistochemistry, which increment the accuracy of prostate cancer diagnosis and may provide relevant information to guide patient management.     

Prediagnostic plasma vascular endothelial growth factor levels and risk of prostate cancer.

Vascular endothelial growth factor (VEGF) plays important roles in endothelial cell proliferation, vascular permeability, and angiogenesis that may be critical to prostatic carcinogenesis and progression. Plasma VEGF levels were significantly greater in patients with metastatic prostate cancer compared with those with localized disease or healthy controls, and plasma VEGF level at prostate cancer diagnosis was an independent prognostic marker for survival in patients with hormone refractory prostate cancer. We therefore examined the association between prediagnostic plasma VEGF levels and risk of prostate cancer and disease phenotype. Using plasma samples obtained in 1982 from healthy men enrolled in the Physicians' Health Study, we conducted a nested case-control study among 504 men diagnosed with prostate cancer during 13 years of follow-up and 520 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using multivariate logistic regression. Prediagnostic plasma VEGF levels were similar among cases and controls. Plasma VEGF concentration was not associated with subsequent risk of prostate cancer (third versus first tertile OR, 1.09; 95% CI, 0.80-1.49; P(trend) = 0.65). Furthermore, no association was observed among men with advanced (stage C or D) prostate cancer or among those who died of prostate cancer. Our results indicate that prediagnostic circulating VEGF levels are not associated with prostate cancer development and have limited value in predicting future risk of prostate cancer.     

Long-term aspirin use and the risk of total, high-grade, regionally advanced and lethal prostate cancer in a prospective cohort of health professionals, 1988-2006

Experimental studies suggest a role for aspirin in the chemoprevention of prostate cancer and epidemiological evidence supports a modest inverse association between regular aspirin use and prostate cancer risk, especially for advanced disease. In a prospective cohort study of 51,529 health professionals aged 40-75 years at baseline, we evaluated long-term aspirin use and the incidence of total, high-grade (Gleason 8-10, n = 488), regionally advanced (T3b-T4 or N1, n = 228) and lethal prostate cancer (M1, bony metastases or prostate cancer death, n = 580) from 1988-2006. We used Cox proportional hazards regression to evaluate risk associated with frequency (days/week), quantity (tablets/week), recency and duration of aspirin use after multivariable adjustment for confounders and other predictors of prostate cancer risk. A total of 4,858 men were diagnosed with prostate cancer during the 18-year study period. Men taking ≥ 2 adult-strength aspirin tablets a week had a 10% lower risk of prostate cancer (p-for-trend = 0.02). For regionally advanced cancer, we observed no significant associations with aspirin use. For high-grade and lethal disease, men taking ≥ 6 adult-strength tablets/week experienced similar reductions in risk hazard ratio [HR = 0.72 (95% confidence intervals [CI]: 0.54, 0.96) and HR = 0.71 (95% CI: 0.50, 1.00)]. Analytical approaches to address bias from more frequent prostate-specific antigen screening among aspirin users did not yield different conclusions. We observed reductions in the risk of high-grade and lethal prostate cancer associated with higher doses of aspirin, but not with greater frequency or duration, in a large, prospective cohort of health professionals. Our data support earlier observations of modest inverse associations with advanced prostate cancer.     

Diet, lifestyle and risk of prostate cancer

Prostate cancer has become a major public health problem worldwide. Yet, the etiology of prostate cancer remains largely unknown. Dietary factors, dietary supplements, and physical activity might be important in the prevention of the disease. In the majority of studies, it was observed that high consumption of meat and dairy products has been linked to a greater risk. In contrast, frequent consumption of fatty fish and tomato products has been associated with a reduced risk. It has been shown consistently that high levels of circulating insulin-like growth factor 1 (IGF-1) are associated with an increased risk of prostate cancer. Dietary factors are also recognized as determinants of circulating IGF-1, thus changes in diet may influence IGF-1 concentrations in serum. Furthermore, increased intake of vitamin E and selenium (from supplements) has been shown in intervention studies to decrease the risk. Possibly, high level of physical activity is also associated with decreased risk of prostate cancer. The accumulated scientific evidence concerning the associations between diet, lifestyle, and risk of prostate cancer development suggests that there are some identified modifiable risk factors that it might be recommended to change in order to decrease the risk for this common cancer site.     

The impact of CAG repeats in exon 1 of the androgen receptor on disease progression after prostatectomy

BACKGROUND: The authors examined the impact of the number of CAG repeats in exon 1 of the androgen receptor on disease progression among men with prostate carcinoma after prostatectomy. This polymorphism has been associated with alterations in activity of the androgen receptor in in vitro systems and with the risk of clinically diagnosed prostate carcinoma in some epidemiologic studies. An earlier series found that, among men at low risk of progressive disease, a small number of CAG repeats predicted a high risk of recurrence, and the impact of CAG repeats varied among men with different risks of progressive disease. METHODS: The authors analyzed specimens from a large clinical series of fixed tissue specimens from men who underwent prostatectomy at a single institution, including 413 American white men (WM) and 298 African-American men (AAM), with 5-10 years of available clinical follow-up. RESULTS: There was little association between the number of CAG repeats and extent of disease, Gleason score, and preoperative PSA level at diagnosis. Overall, patients who had > 18 CAG repeats had a greater risk of recurrence compared with patients who had 18 CAG repeats had an estimated 52% increased risk of disease recurrence. The increased risk could be attributed to men who were at high risk of recurrence.     

Prostate carcinoma presentation,diagnosis, and staging: an update form the National Cancer Data Base

BACKGROUND: Based on the 1998 Patient Care Evaluation (PCE) from the American College of Surgeons National Cancer Data Base (NCDB), the authors described contemporary nationwide patterns of prostate carcinoma presentation, diagnosis, and staging. METHODS: The authors reviewed 54,212 cases from the 1998 PCE. Demographics, presenting signs and symptoms, tumor characteristics, prostate biopsy techniques, and use of staging modalities were evaluated. RESULTS: The mean age of patients in the sample was 68 years. Among patients with available data, 87.5% had a prostate specific antigen (PSA) level of 4 ng/mL or higher, 83.1% had American Joint Committee on Cancer (AJCC) Stage I-II lesions, 80.2% had well or moderately differentiated cancers, and 68.7% of newly diagnosed patients were asymptomatic. Compared with symptomatic patients, asymptomatic patients were more likely to have localized disease (84.6% vs. 78.2%, P < 0.01) and well or moderately differentiated tumors (82.2% vs. 74.6%, P < 0.01). Transrectal ultrasound-guided prostate biopsy was the most common method of tissue confirmation (45.4%). Radionuclide bone scintigraphy was the most frequently employed staging modality (48.7%). Use of various staging evaluations was more frequent among patients at increased risk for disseminated disease (PSA > 10 ng/mL and/or high-grade tumors) versus patients at lower risk (PSA < or = 10 and low to moderate-grade tumors) for metastatic disease (P < 0.005). CONCLUSIONS: Most newly diagnosed patients with prostate carcinoma are asymptomatic and have moderately differentiated and organ-confined disease. Compared with symptomatic patients, tumors in asymptomatic men are associated with lower pretreatment PSA levels, AJCC stage, and tumor grade. Selective use of staging evaluations, based on risk of metastatic disease, may be relatively uncommon. The NCDB remains a unique and rich source of novel patient care information and serves as a national point of reference for prostate carcinoma presentation, diagnosis, and staging.     

Dietary patterns and risk of prostate cancer in U.S. men.

We prospectively investigated the associations between dietary patterns and risk of prostate cancer in the Health Professionals Follow-up Study. Between 1986 and 2000, 3,002 incident prostate cancer cases were identified in our cohort. Using factor analysis, two major dietary patterns were identified, a prudent and a western dietary pattern. Dietary patterns were not appreciably associated with risk of total prostate cancer. For the highest versus the lowest quintiles, the multivariable relative risk (RR) for the prudent pattern was 0.94 [95% confidence interval (CI), 0.83-1.06], and for the western pattern, the multivariable RR was 1.03 (95% CI, 0.92-1.17). Neither were these associated with risk of advanced prostate cancer [highest versus lowest quintile, prudent pattern (RR, 1.01; 95% CI, 0.68-1.49); western pattern (RR, 1.13; 95% CI, 0.77-1.67)]. Higher western pattern scores were suggestively associated with a greater risk of advanced prostate cancer among older men [highest versus lowest quintile (RR, 1.35; 95% CI, 0.97-1.90)], but not after adding processed meat to the model [highest versus lowest quintile (RR, 1.11; 95% CI, 0.75-1.65)]. We did not find any evidence for a protective association between prudent pattern and risk of prostate cancer. The lack of association between a western dietary pattern as identified by factor analysis in our cohort and prostate cancer risk suggests that dietary risk factors for prostate cancer are likely to differ from those for other conditions, such as cardiovascular disease and type 2 diabetes, that have been associated with a western dietary pattern in this cohort.     

Salvage reirradiation for locoregional failure after radiation therapy for prostate cancer: Who,when, where and how?

Even in the current era of dose-escalated radiotherapy for prostate cancer, biochemical recurrence is not uncommon. Furthermore, biochemical failure is not specific to the site of recurrence. One of the major challenges in the management of prostate cancer patients with biochemical failure after radiotherapy is the early discrimination between those with locoregional recurrence only and those with metastatic disease. While the latter are generally considered incurable, patients with locoregional disease may benefit from emerging treatment options. Ultimately, the objective of salvage therapy is to control disease while ensuring minimal collateral damage, thereby optimizing both cancer and toxicity outcomes. Advances in functional imaging, including multiparametric prostate MRI, abdominopelvic lymphangio-MRI, sentinel node SPECT-CT and/or whole-body PET/CT have paved the way for salvage radiotherapy in patients with local recurrence, microscopic nodal disease limited to the pelvis or oligometastatic disease. These patients may be considered for salvage reirradiation using different techniques: prostate low-dose or high-dose rate brachytherapy, pelvic and/or lomboaortic image-guided radiotherapy with elective nodal irradiation, focal nodal or bone stereotactic body radiation therapy (SBRT). An individualized approach is recommended. The decision about which treatment, if any, to use will be based on the initial characteristics of the disease, relapse patterns and the natural history of the rising prostate specific antigen (PSA). Preliminary results suggest that more than 50% of patients who have undergone salvage reirradiation are biochemically relapse-free with very low rates of severe toxicity. Large prospective studies with a longer follow-up are needed to confirm the promising benefit/risk ratio observed with salvage brachytherapy and or salvage nodal radiotherapy and/or bone oligometastatic SBRT when compared with life-long palliative hormones.     

Concurrent chemoradiation for high-risk prostate cancer

There are estimated to be 220800 cases of prostate cancer diagnosed in 2015, making up 26% of all cancer diagnoses. Fortunately, adenocarcinoma of the prostate is often a highly treatable malignancy. Even though the majority of prostate cancer patients present with localized disease, prostate cancer still accounts for over 27000 deaths a year. There is a subset of patients that are likely to recur after locoregional treatment that is thought of as a “high-risk” population. This more aggressive subset includes patients with clinical stage greater than T2b, Gleason score greater than 7, and prostate specific antigen greater than 20 ng/dL. The rate of biochemical relapse in this high risk group is 32%-70% within five years of definitive focal therapy. Given these discouraging outcomes, attempts have been made to improve cure rates by radiation dose escalation, addition of androgen depravation therapy, and addition of chemotherapy either sequentially or concurrently with radiation. One method that has been shown to improve clinical outcomes is the addition of chemotherapy to radiotherapy for definitive treatment. Concurrent chemoradiation with 5-fluorouracil, estramustine phosphate, vincristine, docetaxel, and paclitaxel has been studied in the phase I and/or II setting. These trials have identified the maximum tolerated dose of chemotherapy and radiation that can be safely delivered concurrently and established the safety and feasibility of this technique. This review will focus on the addition of concurrent chemotherapy to radiotherapy in the definitive management of high-risk prostate cancer.     

Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer

BACKGROUND: The use of androgen deprivation therapy (ADT) in the treatment of men with prostate cancer has risen sharply. Although cardiovascular disease is the most common reason for death among men with prostate cancer who do not die of the disease itself, data regarding the effect of ADT on cardiovascular morbidity and mortality in men with prostate cancer are limited. In the current study, the authors attempted to measure the risk for subsequent cardiovascular morbidity in men with prostate cancer who received ADT. METHODS: A cohort of newly diagnosed men in a population-based registry who were diagnosed between 1992 and 1996 were identified retrospectively. A total of 22,816 subjects were identified after exclusion criteria were applied. Using a multivariate model, the authors calculated the risk of subsequent cardiovascular morbidity in men with prostate cancer who were treated with ADT, as defined using Medicare claims. RESULTS: Newly diagnosed prostate cancer patients who received ADT for at least 1 year were found to have a 20% higher risk of serious cardiovascular morbidity compared with similar men who did not receive ADT. Subjects began incurring this higher risk within 12 months of treatment. However, Hispanic men were found to have a lowered risk for cardiovascular morbidity. CONCLUSIONS: ADT is associated with significantly increased cardiovascular morbidity in men with prostate cancer and may lower overall survival in men with low-risk disease. These data have particular relevance to decisions regarding the use of ADT in men with prostate cancer in settings in which the benefit has not been clearly established. For men with metastatic disease, focused efforts to reduce cardiac risk factors through diet, exercise, or the use of lipid-lowering agents may mitigate some of the risks of ADT.