PDF Ebook The biological nature of prostate cancer – a basis for new treatment approaches
The statistics for prostate cancer make alarming reading and set undoubted challenges for oncological research. In the Western world, where the incidence is highest, a man has a 10–11% chance of developing clinically apparent prostate cancer, and a 3–4% chance of dying from the disease [1]. Worldwide the incidence of prostate cancer is rising annually by 2–3% [2]. In 1986 a quarter of a million cases of prostate cancer were diagnosed and at least half a million cases were expected by the turn of the last century [2,3]. In many countries prostate cancer is now the second leading cause of cancer-related death [4] and in Northern Europe it has already taken number one position as the leading cause of cancer-related death in males [4]. The incidence has increased recently, largely due to better and earlier detection, but also because of the general aging of the world’s population and hence an increase in the proportion of men aged over 65 years old in whom the disease is known to be prevalent. In the USA, although signs are that the rate of increase in incidence is falling slightly, it is predicted that in the next 50 years the number of deaths from this disease could increase by 50% [5]. Translated into actual figures these statistics mean that, in the USA in 1999, there were an estimated 179,300 new cases and 37,000 deaths [6]. Similarly, in Europe, assuming that age-specific rates of prostate cancer remain at 1980 levels, the number of men aged over 65 years with prostate cancer is expected to rise from 79,453 in 1990 to 92,240 in 2000. The rise will be most pronounced in those countries with the greatest increase in life expectancy – France, Germany and Spain – and will be further exacerbated as the post-war ‘baby-boomers’ reach their fifties [5].
Despite its high incidence, knowledge and understanding of the pathophysiology of prostate cancer remains rudimentary. A clearer understanding of the biological nature of the disease could have a real impact on its management. Much progress has been made towards understanding the development and progression of prostate cancer and the factors, which drive the development of androgen independence.
There still remain many enigmas about the pathophysiology of prostate cancer. Evidence indicates that the disease is present histologically many years and even decades before clinically significant prostate cancer can be detected. Sakr et al (1993) showed that prostatic intraepithelial neoplasia (PIN) and foci of histological cancer are present at an early age [7]. They concluded that the factors which initiate clinically significant prostate cancer must occur at a young age and that clinically relevant prostate cancer must develop over a much longer period of time than originally postulated. [7]. There is also some data that suggests a higher prevalence of PIN in African-American men than in Caucasian men [8]. However, it still remains unclear why one in four men aged 40–50 years have evidence of foci in the prostate gland while only 1:2000 will go on to develop cancer. Cell turnover is known to be high in prostate cancer; even higher than that observed in testicular cancer. However, disease progression is slow; a man may have malignant cells in the prostate gland for years before the disease becomes clinically significant.
In terms of management, the lack of known markers of tumour aggressiveness to help select patients for more or less aggressive management means that many patients are either over-treated or under-treated. In addition, most patients progress to androgen independence, in which case they become unresponsive to hormonal intervention. At this stage, treatment options are limited to chemotherapy with its concomitant side effects and distressing negative impact on quality of life. Today the factors involved in the development of androgen independence are still being elucidated and therefore it is unclear how to intervene to prevent or delay the process.
Optimal treatment relies on a clear understanding of the disease process, however, it is apparent that there remain significant gaps in knowledge about prostate cancer. A better understanding of the disease is difficult to acquire for the practicing clinician when there is a paucity of reviews summarising the pertinent literature in a way, which is meaningful and on a practical level. This review aims to fulfill this need - to summarise the key facts about the pathophysiology of prostate cancer and highlight their relevance for treatment practice. Although, it is not possible to complete current understanding, but by providing practicing clinicians with the most recent evidence on the biological nature of the disease, we hope to help facilitate more rational decision-making in the treatment of prostate cancer.
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PDF Ebook The biological nature of prostate cancer – a basis for new treatment approaches
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