Young-Age Prostate Cancer
Although prostate cancer is a disease of the elderly, its diagnosis is not uncommonly made in men younger than 55 years. Both ethnic, familial and genetic factors play a role in the early onset of prostate cancer, but the biology, particularly of low-grade prostate cancers detected at young age is not well understood. Autopsy studies have shown a high prevalence of Gleason score 6 prostate cancers in men under 55 years, but mortality of prostate cancer at this young age is almost negligible. Recently, a number of susceptibility genes such as BRCA2 and HOXB13 were reported, each with their own specific biological and histopathology features. In this review, we provide an update on the most recent findings in young-age prostate cancer.
Overview
Prostate cancer is a disease of the elderly with most men diagnosed at the age of 65 years or above. The incidence of prostate cancer rapidly increases after the age of 55 years. During the past few decades, the median age of diagnosis was steadily decreasing, as a consequence of the widespread introduction of prostate-specific antigen (PSA) screening. In the USA (Surveillance Epidemiology and End Result (SEER) data), the median age at diagnosis of prostate cancer dropped from 72 years in 1986 to 66 years in 2011. Since 1977, there was an overall threefold increase of prostate cancer incidence; however, among men aged <55 years in the UK this increase was ninefold. Likely, this trend change is because more men at young age underwent PSA testing, particularly when they would have a positive family history. Furthermore, a baseline PSA testing at the age of 40 years was recommended by American Urological Association, in 2009, as some studies had indicated that increased PSA value at this age would herald the development of a more aggressive cancer at older age. The substantial increase of prostate cancer diagnosis at young age raises today a number of important questions both about their biology and their management. A 60-year-old man with a low-risk, biopsy Gleason score 6, prostate cancer is a suitable candidate for active surveillance, who could defer therapy until signs of grade progression or rapid growth. However, a similar scenario in a 50-year-old man might prompt immediate intervention, taking into account his longer life expectancy and the suspicion that prostate cancer detected at young age might behave more aggressively. This review intends to identify characteristic features of prostate cancer in men at young age as opposed to prostate cancers identified in older men, taking into consideration both histomorphological and molecular-genetic findings.
Autopsy studies can give an insight into the prevalence of asymptomatic or latent prostate cancer in a population. The prevalence of latent prostate cancer in younger men varies markedly among different autopsy series. Breslow et al showed that, on average, about 15% of men aged 45–54 years have latent prostate cancer with a prevalence ranging from 9% to 22%, depending on the geographical distribution of the population. Sakr et al reported that 27% and 34% of men in USA aged 30–40 years and 40–50 years, respectively, harboured a prostate cancer, although there is none with a high-grade component. In a Greek autopsy series, prostate cancer was found only in one among 38 men aged 40–50 years (2.6%). However, in another Mediterranean (Spanish) population, a prevalence of 14.3% was established in this age group. These observations are in contrast to the much higher prevalence of 27% and 34% found in men aged 40–50 years from Hungary and the USA, respectively. Altogether, these observations would indicate that about 20%–30% of older men aged 40–50 years living in the USA and Middle and Northern Europe would harbour a prostate cancer. Importantly, their natural course and biology remain unclear.
The age cut-off to define young-age prostate cancer is somewhat arbitrary. The upper limit of the age range for young-age prostate cancer cited in the literature varies between 50 and 55 years. According to UK and USA epidemiological data, the mortality from prostate cancer at the age under 55 years is extremely low, but starts rising rapidly in men over 55 years. On the other hand, autopsy studies show a high prevalence of latent prostate cancer in the fourth and fifth decades, some of which could be detectable in case of random prostate biopsies prompted by elevated PSA. The European and North American urology associations recommended PSA testing particularly for men aged over 55 years, and as a consequence, it is likely that in the PSA era a larger proportion of prostate cancers discovered in European and American men aged under 55 years were symptomatic as compared with men aged over 55 years. Obviously, a prostate cancer discovered because of the symptoms of metastatic disease is an entirely different disease than a prostate cancer identified merely on the basis of a PSA prompted prostate needle biopsy. The literature occasionally refers to early-onset prostate cancer as a subset of young-age or familial prostate cancers with more aggressive disease and higher prostate-cancer-specific death. Here, we would propose to define early-onset prostate cancer as prostate cancers detected in men aged <55 years with at least one clinical sign of prostate cancer, such as positive digital rectal examination or a visible tumour at time of imaging (at least T2 prostate cancer) rather than a prostate cancer, incidentally detected because of PSA testing alone (T1c). In contrast, young-age prostate cancer could be defined broadly as any prostate cancer, regardless tumour extent or clinical manifestations in men aged <55 years. Although this distinction between young-age and early-onset prostate cancer is not always explicit in the literature, we tried to apply these two definitions for this review on the basis of the populations studied or data provided in the reviewed publications.
Abstract and Introduction
Abstract
Although prostate cancer is a disease of the elderly, its diagnosis is not uncommonly made in men younger than 55 years. Both ethnic, familial and genetic factors play a role in the early onset of prostate cancer, but the biology, particularly of low-grade prostate cancers detected at young age is not well understood. Autopsy studies have shown a high prevalence of Gleason score 6 prostate cancers in men under 55 years, but mortality of prostate cancer at this young age is almost negligible. Recently, a number of susceptibility genes such as BRCA2 and HOXB13 were reported, each with their own specific biological and histopathology features. In this review, we provide an update on the most recent findings in young-age prostate cancer.
Introduction
Overview
Prostate cancer is a disease of the elderly with most men diagnosed at the age of 65 years or above. The incidence of prostate cancer rapidly increases after the age of 55 years. During the past few decades, the median age of diagnosis was steadily decreasing, as a consequence of the widespread introduction of prostate-specific antigen (PSA) screening. In the USA (Surveillance Epidemiology and End Result (SEER) data), the median age at diagnosis of prostate cancer dropped from 72 years in 1986 to 66 years in 2011. Since 1977, there was an overall threefold increase of prostate cancer incidence; however, among men aged <55 years in the UK this increase was ninefold. Likely, this trend change is because more men at young age underwent PSA testing, particularly when they would have a positive family history. Furthermore, a baseline PSA testing at the age of 40 years was recommended by American Urological Association, in 2009, as some studies had indicated that increased PSA value at this age would herald the development of a more aggressive cancer at older age. The substantial increase of prostate cancer diagnosis at young age raises today a number of important questions both about their biology and their management. A 60-year-old man with a low-risk, biopsy Gleason score 6, prostate cancer is a suitable candidate for active surveillance, who could defer therapy until signs of grade progression or rapid growth. However, a similar scenario in a 50-year-old man might prompt immediate intervention, taking into account his longer life expectancy and the suspicion that prostate cancer detected at young age might behave more aggressively. This review intends to identify characteristic features of prostate cancer in men at young age as opposed to prostate cancers identified in older men, taking into consideration both histomorphological and molecular-genetic findings.
Prevalence
Autopsy studies can give an insight into the prevalence of asymptomatic or latent prostate cancer in a population. The prevalence of latent prostate cancer in younger men varies markedly among different autopsy series. Breslow et al showed that, on average, about 15% of men aged 45–54 years have latent prostate cancer with a prevalence ranging from 9% to 22%, depending on the geographical distribution of the population. Sakr et al reported that 27% and 34% of men in USA aged 30–40 years and 40–50 years, respectively, harboured a prostate cancer, although there is none with a high-grade component. In a Greek autopsy series, prostate cancer was found only in one among 38 men aged 40–50 years (2.6%). However, in another Mediterranean (Spanish) population, a prevalence of 14.3% was established in this age group. These observations are in contrast to the much higher prevalence of 27% and 34% found in men aged 40–50 years from Hungary and the USA, respectively. Altogether, these observations would indicate that about 20%–30% of older men aged 40–50 years living in the USA and Middle and Northern Europe would harbour a prostate cancer. Importantly, their natural course and biology remain unclear.
Definition of Young-age and Early-onset Prostate Cancer
The age cut-off to define young-age prostate cancer is somewhat arbitrary. The upper limit of the age range for young-age prostate cancer cited in the literature varies between 50 and 55 years. According to UK and USA epidemiological data, the mortality from prostate cancer at the age under 55 years is extremely low, but starts rising rapidly in men over 55 years. On the other hand, autopsy studies show a high prevalence of latent prostate cancer in the fourth and fifth decades, some of which could be detectable in case of random prostate biopsies prompted by elevated PSA. The European and North American urology associations recommended PSA testing particularly for men aged over 55 years, and as a consequence, it is likely that in the PSA era a larger proportion of prostate cancers discovered in European and American men aged under 55 years were symptomatic as compared with men aged over 55 years. Obviously, a prostate cancer discovered because of the symptoms of metastatic disease is an entirely different disease than a prostate cancer identified merely on the basis of a PSA prompted prostate needle biopsy. The literature occasionally refers to early-onset prostate cancer as a subset of young-age or familial prostate cancers with more aggressive disease and higher prostate-cancer-specific death. Here, we would propose to define early-onset prostate cancer as prostate cancers detected in men aged <55 years with at least one clinical sign of prostate cancer, such as positive digital rectal examination or a visible tumour at time of imaging (at least T2 prostate cancer) rather than a prostate cancer, incidentally detected because of PSA testing alone (T1c). In contrast, young-age prostate cancer could be defined broadly as any prostate cancer, regardless tumour extent or clinical manifestations in men aged <55 years. Although this distinction between young-age and early-onset prostate cancer is not always explicit in the literature, we tried to apply these two definitions for this review on the basis of the populations studied or data provided in the reviewed publications.