PROSTATE HISTOSCANNING
 
What is Prostate Cancer?
Prostate cancer occurs when malignant (cancer) cells form in the glandular tissue of the prostate. The prostate is a small gland in the male reproductive system that sits just below the bladder and in front of the rectum. The gland surrounds the male urinary tract (or urethra) and produces fluid that makes up part of the semen. When detected and treated early, prostate cancer can often be managed successfully.  
Facts about Prostate Cancer
  • Prostate cancer is the most common non-skin malignancy and second leading cause of male cancer deaths after lung cancer.
  • In recent years, evidence suggests an increasing trend in prostate cancer incidence in most countries around the world, with higher incidence in the USA and Northern Europe (including the UK), whilst mortality has decreased.
  • Prostate cancer is uncommon in younger men, with over half of all new cases diagnosed in men aged 70 or more.
  • Men are more likely to die with prostate cancer than from it, as suggested by the large disparity in lifetime risk ofdiagnosis vs. the lifetime risk of disease-related death. Prostate cancer behaves in different ways.
  • Most tumours are slow-growing and may remain dodsrmant for some time before they progress. These are unlikely to cause significant clinical symptoms during a man's life. In some cases however, cancer can grow rapidly and spread to other parts of the body.
 
Prostate Cancer Statistics
USA EU* UK
Prevalence 2 million1 >1 million2 80,0003
Age-adjusted incidence  rate per 100,000 1681 (in 2004) 20-913 (in 2002) 1204 (in 2004)
Total incidence 219,0005 202,0006 35,0004
Percent of all cancer diagnosis in men 29%5 (1 in 3) 18%6 (1 in 6) 24%4 (1 in 4)
Age-adjusted death rate per 100,000 271 237 (in 2002) 254
Total cancer-related deaths 27,0005 68,0006 10,0004
5-year survival rate 98%1 77.5%8 70%9
Percent of all cancer deaths in men 9%5 10.4%6 13%4
Lifetime risk of diagnosis 18%5 (1 in 6) 6%6 (1 in 16) 7%4 (1 in 14)
Lifetime risk of dying 3.1%5 (1 in 33) 1.1%6 (1 in 90) 4%4 (1 in 25)
* The 25 EU countries.
Diagnosing Prostate Cancer
Timely detection of prostate cancer may be achieved using one or a combination of several methods, such as digital rectal examination (DRE), measurement of serum PSA, transrectal ultrasonography (TRUS) and other imaging modalities. There is currently no definitive diagnostic test that can reliably predict which tumour will be slow growing and which will become more aggressive. This renders decisions about cancer screening and management difficult.
Prostate specific antigen test: The PSA test is a minimally invasive test that measures the level of Prostate Specific Antigen (PSA) in the blood. PSA is produced in the prostate gland. Its principal role is to liquefy semen. It exists in very high concentrations in the semen. Some, however, finds its way into the bloodstream. In small healthy prostates the amount of PSA that makes it into the blood stream is small. If the prostate is enlarged or inflamed or infected the amount of PSA finding its way into the blood stream will usually be increased. Because prostate cancer results in a disruption of the usual cell-cell architecture within the prostate and also encourages a new but abnormal blood supply to be formed to support the growth of the cancer its presence will also invariably result in higher levels of PSA getting into the blood than would be expected to be there if cancer were not present. It is this proportionally higher blood (serum) PSA in the presence of cancer that we use to identify men who will be at higher risk of harbouring the disease. PSA is currently the strongest predictive test for early detection of asymptomatic prostate cancer (sensitivity of up to 80% and a Positive Predictive Value (PPV) of up to 50% in men whose PSA level is >4ng/mL)10. Unfortunately the test is not cancer-specific and not completely reliable. Conditions other than cancer (e.g. enlargement of the prostate, prostatitis, and urinary infection) can cause a rise in PSA levels. Furthermore, it is shown that about two thirds of men who have elevated PSA, do not have prostate cancer11. Nevertheless, these will be referred for prostate biopsies and may suffer the anxiety, discomfort and risk of follow-up investigations. Similarly, up to 27% of men with prostate cancer have a PSA level of < 4.0 ng/mL (i.e. a level considered to be "normal") and as many as 25% of these men (7% in total) will have a high-grade or clinically aggressive form of the disease (i.e. Gleason score =7)11.
Digital Rectal Examination (DRE): DRE is a standard procedure used in routine urological examination, during which the physician palpates the prostate. The test has limited reproducibility and can vary widely among physicians. It is also shown to have a poor sensitivity for staging prostate cancer (up to 60%)12 and a lower predictive value than PSA (PPV of about 10%)10. Nevertheless it may detect asymptomatic cancers in some men with a low PSA value. It is therefore generally accepted that any abnormality found during DRE should prompt prostate biopsy.
Trans Rectal Ultrasound (TRUS): TRUS is a widely available test that is easy to manage in an outpatient clinic and is less expensive than other available imaging modalities such as MRI. However there are many questions about the interpretation of the ultrasound scans. TRUS can detect cancer as an hypoechoic lesion on the scan, but only in 60% of cancer cases13. Furthermore, the finding of an hypoechoic lesion is not specific to prostate cancer, as it may also be observed in benign processes such as prostatitis or infection12. Although TRUS is insufficient for cancer detection it has become indispensable for conducting prostate biopsies.
Biopsy: PSA testing, DRE, and TRUS do not diagnose prostate cancer either independently or collectively. They only establish the likelihood that prostate cancer may be present. The only way to make a definitive positive diagnosis of prostate cancer today is to perform a biopsy followed by histopathological examination. The prostate is one of the few remaining human organs where biopsies are carried out blindly. Even with TRUS-guided needle biopsy, the reference procedure for the diagnosis of prostate cancer, only a small fraction of the gland is taken per sample or core, and will inevitably miss some cases of cancer. Data from the USA (PLCO trial) shows cancer was detected in about 1 in every 3 men14 who underwent biopsy. Also, a negative biopsy result does not completely exclude cancer as up to 30% of men with an initial negative biopsy are found to have cancer with a subsequent biopsy13.
Other imaging tests: Several additional imaging tests are available for prostate cancer such as computerized tomography scans (CT-scans), and magnetic resonance imaging (MRI). These are relatively expensive procedures that are mainly used to determine the extent to which cancer may have spread outside the prostate.
On receipt of biopsy tissue, the pathologist's task is to estimate the extent of cancer within each core. This is normally measured in mm or as a percentage of the length of the core. The pathologist's second task is to grade the tumour with respect to its likely biological aggressiveness. Although a rather unusual approach he assigns a numerical value to the predominant pattern of tumour within each core. The range available to the pathologist varies from 1-5. However, these days it is rare for a pathologist to attribute a score of less than 3. The reason for this is that, on current criteria, tissue assigned a score of less than 3 rarely has the attributes of cancer. Once the predominant pattern has been assigned the pathologist assigns a secondary score. This is given to the next most predominant pattern of prostate cancer within the specimen. The scores can be presented individually (for example 3 + 3) or as the sum of the two, in this case as the number 6. This scoring system was devised by a pathologist called Gleason and therefore is widely referred to as the Gleason score and or the Gleason sum. Attributing a Gleason score to tissue remains a relatively subjective process and is dependent on the skill and expertise of the examining pathologist.
Treating Prostate Cancer
There are several management options available for men with prostate cancer. The choice of therapy is influenced principally by the probability of achieving a cure but also by other factors such as patient life-expectancy, co-morbidities, potential side-effects and patient preference. Possible options may include surgery, radiation therapy, cryosurgery, HIFU (High Intensity Focused Ultrasound), hormone therapy, or a combination, as well as active surveillance. There is today no conclusive evidence that one particular option is superior to another in terms of survival. This has led to a wide variation in therapy utilization, which may impact the quality of care.
Radical prostatectomy: involves surgery to remove the entire prostate gland, with the intention of cure by eliminating all cancer cells. However complete tumour clearance is not always achieved with up to 40% of men who undergo surgery being found to have capsular invasion or positive resection margins with associated risk of cancer recurrence. Although severe or life-threatening complications associated with this surgery are rare, it is shown that up to two thirds of men may have impaired erectile function or impotence as a result of radical prostatectomy and as many as 50% of operated men have urinary incontinence one year later15. Other complications may include excessive intra-operative bleeding and infection at the incision site. Additionally, some men may not be considered for surgery due to their age or existing co-morbidity.
Radiotherapy: involves the use of radiation to kill cancer cells or keep them from growing. Two approaches are used, mainly external-beam radiotherapy (EBRT) using high-energy x-rays, and brachytherapy using internal radioactive implants. Complications due to radiation exposure include bladder irritation (urgency, pain) in nearly 5% of men and impotence in up to 50% of patients16. Because this procedure does not eliminate the entire prostate gland, successful treatment is more difficult to define.
High Intensity Focused Ultrasound (HIFU): radical treatment is associated with significant morbidities and quality of life impact. This risk versus the reward is not acceptable to many physicians and patients and has motivated the development of minimally invasive therapies such as HIFU. HIFU is a minimally invasive treatment that requires no incision. Treatment is accomplished by systematically pulsing high energy ultrasound waves throughout a tumour volume, which results in its ablation. Although it is a relatively new technique, early studies are encouraging. HIFU treatment is shown to have a disease free rate (i.e. negative biopsy and PSA < 4.0ng/ml) of nearly 72% and appears to be associated to a lower rate of impotence and incontinence then radical prostatectomy17.
Active surveillance: because not all diagnosed cancers require immediate therapy, active surveillance is an alternative to invasive treatment, mainly used in low-grade cancers. Regular follow-up tests, including biopsies may be performed to monitor the evidence of the progression of cancer with the prospect of offering deferred curative treatment should the tumour be seen to progress. The advantage of this is that many men avoid the side effects of radiotherapy and surgery. But the disadvantages are that the patient might miss the window of opportunity for a cure if an aggressive form of cancer does eventually develop and patient anxiety due to their continual confrontation with the disease.
Clinical Challenges of Prostate Cancer
Overdiagnosis vs. underdiagnosis: Although timely cancer detection improves a patient's chance of cure, the overall benefit of prostate screening is still controversial and is currently being assessed in two large clinical trials in Europe (ESRPC) and PROTECT in the UK, and in the United States (PLCO trial). However, the final results are not expected for several years. Because screening is mainly PSA driven, there is a growing concern today that many, if not most of the detected cancers may be clinically insignificant and may not require immediate radical treatment. It is indeed shown that PSA-screening has led to a higher detection of small volume, low grade and organ confined cancers that are diagnosed earlier in their natural course16. This results in overdiagnosis i.e. a frequent discovery of indolent cancers that would otherwise remain clinically unrecognized during the patient's natural lifespan. Overdiagnosis is exacerbated by the fact that the PSA thresholds for biopsy are decreasing around the world due to the risk of underdiagnosis and missing aggressive cancers in low PSA ranges. In a recent ERSPC report, instances of overdiagnosis were identified in up to 60% of prostate cancer cases16. If this estimate is accurate, the potential impact of overdiagnosis and unnecessary treatment on patients' health and its burden to healthcare services would be substantial.
Choice of treatment: The main challenge in prostate cancer treatment is to distinguish between indolent cancers, which require active surveillance or conservative management, and those cancers at high-risk of local and distant spread which may warrant radical therapy. In the latter, the survival benefits of radical therapy may outweigh the associated side effects of treatment. In addition, some cancers may evolve from being slow to fast growing, and it is therefore important to detect this change in time so that the course of the treatment can be changed while the disease is still curable.
Total Economic Burden of Prostate Cancer: The economic burden of prostate cancer is substantial and likely to grow given the ageing of the population and the increasing use of screening around the world. In the USA alone, estimates of the total cost of prostate cancer (including screening, diagnosis, treatment, and monitoring) ranged from $5 billion to well over $10 billion per year18. While in the UK, the total annual expenditures for prostate cancer reached £92.8 million, in 200219. Whereas the increase in prostate cancer screening has enabled the detection of cancer earlier and at a potentially curable stage, it has also resulted in overdiagnosis of indolent tumours and unnecessary biopsies for men with false-positive screening tests. In Sweden, it is shown that the use of PSA tests has increased seven fold and radical prostatectomies have increased six fold between 1991 and 2002, while radiation therapy increased ten fold from 1997 to 200220. A similar trend is likely in the USA with a 243% increase in radical prostatectomy procedures between 1989 and 200221. To achieve a better quality of care for men with prostate cancer and to be more cost effective, it is being suggested that patients should be treated more discerningly. New diagnostic tools are needed to reduce the rate of false positives and reliably discriminate between those men with latent cancers and those with more aggressive forms of the disease.
References
1. Cancer of the prostate. Surveillance Epidemiology and End Results (SEER). http://seer.cancer.gov/
2. European prostate cancer coalition, Europa Uomo. http://cancerworld.org
3. Globocan 2002, IARC. www.iarc.fr
4. UK Prostate Cancer Statistics. Cancer Research UK. http://info.cancerresearchuk.org/
5. Ahmedin J, Siegel R, Ward E, et al. Cancer Statistics, 2007. CA Cancer J Clin 2007 ;57 :43-66.
6. Boyle P, Ferlay J. Cancer Incidence and mortality in Europe, 2004. Annals of Oncology 2005;16:481-488.
7. European Commission Health Status Indicators (2002).
http://ec.europa.eu/health/ph_information/dissemination/echi/echi_2_en.htm
8. Verdecchia A. et al. Recent cancer survival in Europe: a 2000-02 period analysis of EUROCARE-4 data.
9. Melia J. Part1: The burden of prostate cancer. BJU International 2005;3:4-15.
10. Crawford D and Thompson IM. Controversies regarding screening for prostate cancer. BJU International 2007;2:5-7.
11. Thompson IM Pauler DK, Goodman PJ et al. Prevalence of prostate cancer among men with a prostate-specific antigen level =4.0 ng per milliliter. N Engl J Med 2004;350: 2239-46.
12. Van Der Cruijsen-Koeter et al. The value of current diagnostic tests in prostate cancer screening. BJU International 2001;88:458-466.
13. Grossfeld GD and Carroll PR. Prostate cancer Early Detection: a clinical perspective. Epidemiol Rev 2001;23:173-180.
14. Andriole GL, Levin DL, Crawford D et al. Prostate Cancer Screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial: Findings From the Initial Screening Round of a Randomized Trial. Journal of National Cancer Institute 2005;97:433-438.
15. Harris R and Lohr K. Screening for Prostate Cancer: An Update of the Evidence for the U.S. Preventive Services Task Force. Annals of Internal Medicine 2002;137:917-926.
16. Bangma CH, Roemeling S, and Shröder FH. Overdiagnosis and overtreatment of early detected prostate cancer. World J Urology 2007;25:3-9
17. Rewcastle JC. High Intensity Focused Ultrasound for Prostate Cancer : Clinical Results and Technological Evolution. University of Calgary, Alberta, Canada.
18. DiSantostefano RL and Lavelle JP. The Economic Impact of Prostate Cancer Screening and Treatment. NC Med J 2006;67:158-160.
19. Sangar VK, Ragavan N, Matanhelia S et al. The economic consequence of prostate and bladder cancer in the UK. BJU International 2005;95:59-63.
20. Sennfält K, Carlsson P, Varenhorst E. Diffusion and Economic Consequences of Health Technologies in Prostate Cancer Care in Sweden, 1999-2002. Eur Urol 2006;49:1028-34.
21. Saigal CS, Litwin MS. The economic costs of early stage prostate cancer. Pharmacoeconomics 2002;20:869-878.
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