Prostate Cancer in the United States of America - Research Paper Example

ABSTRACT The current document aims to provide a comprehensive description of the burden of prostate cancer in the United States of America. The cancer of the prostate gland is one of the major leading causes of death of men especially of advanced age. The disease has a high incidence and prevalence and the incidence rates are reported to be on a rise due to better technology available for early diagnosis and life style changes. The paper also attempts to explore the major risk factors that have been reported to be associated with the development of prostate cancer. Finally it presents the review of a recent research article exploring the comparative efficacy of cryoablation and radiotherapy as the intervention strategies for the treatment of histologically evidenced localized prostate cancer. PROSTATE CANCER INTRODUCTION Prostate glands, an integral part of the male reproductive system is a walnut sized gland located in between the penis and the rectum, under the urinary bladder. Cancer of the prostate glands involves a multifocal primary tumor of varying intensities. The primary tumors originate from the epithelial cells of the prostate and produce a range of prostate cancer associated antigens such as prostatic acid phosphatase, human kallikrein 2, prostate stem cell antigen and prostate specific membrane antigen along besides the prostate specific antigen (PSA) or human kallikrein 3. These tumors respond to androgen and their growth is at least partially regulated by it; though in advanced stages they cease to remain androgen dependent and enter the scattered disease state. Lymph nodes and skeleton at this stage exhibit metastases with bones being exceptionally vulnerable to prostate cancer. Moreover, unlike most other tumors, metastases in bone disturb the normal bone remodeling causing an osteoblastic response distinctive of prostate cancer. Immense pain and morbidity in prostate is attributed to this osteoblastic response (Corey & vessella, 2007). Prostate cancer has been reported to be the second leading cause of death of men in the west and the second most common form of cancer in men (Quinn & Babb, 2002). The incidences, mortality and prevalence of the disease exhibits striking correlation with race, diet and life style patterns. Further significant geographical variations are also observed in the occurrence of the disease. Considering the severity of the disease, and its status as a significant and growing public health problem; the current paper aims to make a comprehensive study of the incidence and prevalence; and the trends in the incidence of prostate cancer in United States of America (USA). Further it also aims to present a review of the inherent risk factors responsible for the observed trends in the incidence of the disease. Finally, a recent research involving a randomized control trial (RCT) to study an intervention strategy for management of prostate cancer is reviewed. BURDEN OF PROSTATE CANCER Three measures are used to estimate the burden of cancer worldwide: incidence, prevalence and mortality. INCIDENCE Incidence refers to number of new cases of a disease occurring in a population per year and is usually expressed either as an absolute number or as rate per 100,000 persons. Incidence is an important measure that provides an estimate of the risk of disease and enables comparisons between different countries or geographical areas and also within a specific population at during different periods (Parkin et al., 2002). The incidence rates for prostate cancer estimated for the year 2008 according to latest SEER (Surveillance Epidemiology and End Results) data gathered for 17 SEER geographic areas in USA was 156.0 per 100,000 man (Howlader et al., 2011). This was lower than the rates estimated for the two preceding years, 170.83 and 173.64 for 2006 and 2007 respectively. During the last decade an initial fall followed by a rise in incidence rates has been reported (Table 1). Table 1: Incidence rates for Prostate Cancer (2001-2008) (Howlader et al., 2011) Year of Diagnosis Incidence rate 2001 185.05 2002 182.51 2003 169.98 2004 165.99 2005 156.28 2006 170.83 2007 173.64 2008 157.04 Age specific data indicates the highest incidence of occurrence of disease in the age group of 65 to 74 (35.3%) followed by 55 to 64 age group (30.7%) and 75-84 age group (19.9%). No cases were reported for the age group 0 to 34. Among the races highest incidences were reported for black (233.8), followed by white (149.5) and Hispanic (107.4). The lowest incidences for the year 2008 were reported for American Indian (75.3) and Asians (88.3). For the period spanning 1975 to 2008; for which data is available there have been significant variations in trends of incidences. In terms of annual percentage change (APC), there has been a rise of 2.6% from year 1975-1988; followed by a further significant rise of 16.5% in the next four years (1988 to 1992). During the following years (1992 to 1995), a significant fall in incidence rates was reported (11.6%) and the condition remained almost stable with a marginal rise 2.2% in the period from 1995 to 2000. During the last 8 years for which data is available (2000 to 2008), there has been a marginal fall of 1.9%). Figure 1: Incidence Rates by States in USA. The ranges of incidence shown by the different colors are: light green (120-148.1), medium green (148.2-160.9), medium blue (161.0-169.8), dark blue (169.9-207.2) (US Cancer statistics working group, 2010) The geographical variations in the incidence rates of the disease are displayed in figure 1. According to the data, incidences of prostate cancer are highest in Northeast US (171.1), and progressively decrease in South (156.2), Midwest (155.5) and West (147.1) (US Cancer statistics working group, 2010). PREVALENCE Prevalence refers to the number of living individual at a particular time, diagnosed with a particular disease. There is difference of opinion regarding criteria of prevalence estimation. While some authors consider ‘ever having been diagnosed with the disease’ as a criteria for prevalence, other consider ‘alive and under treatment or being medically followed up for a disease’ as the eligibility criteria. To enable rational comparisons however, it agreed that individuals alive, diagnosed with the disease and with a maximum of five years of post diagnosis period are included in prevalence estimates (Parkin et al., 2002). The prevalence of prostate cancer reported for July 1, 2008 in USA is 2,355,464 men. The data was gathered using the counting method and hence the prevalence estimates are limited duration estimates. Race specific data indicates the highest prevalence for the specified period for whites (1,984,603) followed by blacks (2, 84,208) (Howlader et al., 2011). MORTALITY Mortality is the number of death and is expressed as rate per thousand persons. In context of a disease, mortality refers to number of death due to the particular disease and is product of disease incidence and fatality. While fatality is the inverse of survival and expresses the probability of an individual dying from a disease; mortality indicates the average risk of dying from a particular cancer in a particular population during a specified period (Parkin et al., 2002). The age adjusted mortality for prostate cancer in USA was reported to be 24.4 per 100,000 men for the period 2004-2008. The highest death rate was observed for the age group 75-84 (39.5%), followed by those above 85 years of age (31.4%). No death was reported for the age group 0 to 34 and besides this the lowest death rates were reported for the age groups 35-44; and 45-54 (1.5%). Mortality rates have been reported to have declined significantly (3.9%) over the years (1998-2007) (Kohler et al., 2011). Data provided by U. S. cancer Statistics working group available till 2007 shows similar trends in results with highest incidence and mortality reported for black followed by white and Hispanic. Geographical variations in mortality indicate highest mortality in Midwest (24.5), followed by South (23.5), Northeast (23.1) and West (22.8) (US Cancer statistics working group, 2010) RISK FACTORS Prostate cancer results as a cumulative impact of several genetic and epigenetic factors that are further influenced by environmental risk factors. The major individual and environmental risk factors associated with the burden of prostate cancer can be listed as (Pienta et al., 1993): Table 2: Risk Factors for Prostate Cnacer Individual Risk Factors Environmental Risk Factors Family History Socioeconomic Factors Race Occupation Smoking Cadmium exposure Sexual Behavior Vasectomy Benign Prostatic Hyperplasia Dietary Factors Hormones Individual Risk Factors There have been substantial data to indicate that individuals with relatives affected by prostate cancer are at higher risk for the development of disease. In accordance the American Cancer screening guide recommends a prostate cancer examination for individuals with the condition in family (Pienta et al., 1993). In terms of race, as has been observed in aforementioned race specific incidence and mortality rates, the white and the black Americans are at a significantly higher risk of the disease compared to Asian and Scandinavian population. However this data cannot be considered as accurate since it does not take in to account the life style, dietary habits and socioeconomic factors; since these factors are also major determining factors for the development of disease (Pienta et al., 1993). Occupation, especially in terms of physical activity has been considered a risk factor for the disease. Further individuals working in industries where they are exposed to cadmium (a trace mineral found in cigarette smoke and alkaline batteries) are found to be at higher risk of developing prostate cancer. No clear evidences for the association of sexual activity to disease development are available (Pienta et al., 1993). Among the dietary factors, a high fat intake has been positively associated with the disease (Muir et al., 1991). Contradicting results for the association of vitamin A is available. Steroid hormones are another set of risk factors that have been positively associated with prostate cancer though the exact mechanism of association of the two is incompletely understood (Pienta et al., 1993). The major cause of difference in the burden of disease in white and African-American men has been attributed to the socioeconomic disparities between the two groups. However there has been no clear evidence available for the same. Studies provide conflicting evidences, that socioeconomic factors are associated as well as not associated with the occurrence of prostate cancer. INTERVENTION STUDY Management of localized prostate cancer is involves watchful waiting, radical prostatectomy, external beam radiotherapy (EBRT), brachytherapy, Cryoablation; however there is a lack of consensus on optimal management technique. A recent study by Donnelly and colleagues (2010) aimed to study the comparative efficacy of radiotherapy to cryolablation for treatment of localized prostate cancer. The study was supported by National Cancer Institute of Canada and involved an unblended, randomized control trial (RCT), and was conducted on a group of 244 men newly diagnosed with localized prostate cancer over the period from December 1997 to February 2003. The selected eligibility criteria included a histologically evidenced adenocarcinoma, T2 or T3 type of tumor, and metastases not reaching lymph nodes or evidence for any other distant metastases. Individuals with a PSA level less than or equal to 20ng/ml na d a gland volume of less than or equal to 60cm3 prior to initiation of treatment were considered eligible for the study. Each of the selected treatment modalities were offered to 122 men randomly, in addition all subjects received neoadjuvant antiandrogen therapy. The primary endpoint selected for disease progression at the end of the three year follow up period was based on trifecta definition: radiologic evidence of metastatic disease, initiation of further antineoplastic therapy, or biochemical failure. Biochemical failure with respect to prostate cancer has been defined as rise in PSA at two consecutive occasions with a final value reaching >1.0ng/ml; a rise beyond the PSA nadir +2ng/ml. The secondary endpoints were selected to be survival and prostate biopsy at 3 yrs. During the 36 month follow up, 23.9% men of cryoablation group were reported to exhibit disease progression, while in the radiotherapy group 23.7% did so. Cancer positive biopsy at 36 month follow up was reported for 7.7% and 28.9% subjects in cryoablation and radiotherapy groups respectively. Overall and prostate cancer specific disease survival was found to be equivalent for both the groups. Thus was a minimal difference (0.2%) in disease progression at 36 month for the two treatment modalities. However since the confidence interval was high (-10.8% to 11.2%), inferiority exists. This is corroborated with longer follow up results which appear to favor cryoablation. Evidences from biopsy were also favorable for cryoablation, compared to radiotherapy. Another major limitation of the study was slow accrual leading to the termination of the trial prematurely. The smaller sample size was also responsible for the high CIs for the differences observed in the two selected groups. Despite the shortcomings the study has been able to provide a comparative account of the various aspects of the cryoablation and radiotherapy for the treatment of prostate cancer. REFERENCES 1 U. S. Cancer Statistics Working Group. (2010). United States Cancer Statistics: 1999–2007 Incidence and Mortality Web-based Report. Atlanta: Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute. Read More