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Prostate Cancer

History

In 1536, prostate was first described by Venetian anatomist Niccol Massas and it

was illustrated by Flemish anatomist Andreas Vesallius in 1538. But since then, prostate

cancer was not identified until 1853. J. A dams (1853), a surgeon at The London

Hospital, described the first case of prostate cancer in which he discovered it by

histological examination and also he noted in his report that it was a very rare disease.

Over the past several decades, surgeries for prostate cancer were executed to relieve

urinary obstruction (B. Lytton, 2001). However, there was no systematic technique for the

removal of the prostate until the pioneering work of Hugh Hampton Young in 1904 who

performed the first radical perineal prostatectomy (H. H. Young, 1905). Later, it became

the standard method for prostatectomy for the next four decades and it was used in an

attempt to achieve curative resection although it was initially performed as a palliative

therapy. In 1890s, orchiectomy (surgical removal of the testes) was first performed to

treat prostate cancer but then it wasnt that successful. After several decades,

transurethral prostatic resection (TURP) became the preference over radical

prostatectomy for the aid of obstructive prostate cancer because it could better preserve

penile erectile function. P. Walsh (1983) developed, a significant advancement through a

modified technique for radical retropubic prostatectomy to enhance control of bleeding.

This approach allows the maintenance of erectile function and sexual potency. Huggins

et al. (1941) was the first to used systemic approach to treat prostate cancer by describing

the effects of treating advanced prostate cancer patients through surgical or medical

castration by means of oral oestrogen administration. To recognize his efforts in his


studies, Charles, Huggins was awarded the Nobel Prize in Physiology and Medicine in

1966. Andrzej W. Schally and Roger Guillemin also both won the 1977 Nobel Prize in

Physiology and Medicine for determining the role of the gonadotropin-releasing hormone

(GnRH) in reproduction. GnRH receptor agonists, such as leuprolide and goserelin, were

subsequently developed and used to treat prostate cancer (Schally, Kastin & Arimura,

1971). In the advent of twentieth century, reports on the use of radiation to treat localized

prostate cancer appeared but then, these techniques, however, were difficult to perform

and it is very uncomfortable for the patient. Concerns in brachytherapy did not pop up

until the 1970s when Willet Whitmore described an open implant techniques using the

radioisotope of iodine.

Pathogenesis

The manner of development of prostate cancer is a complex process. The

androgen signalling pathway and its contact with other pathways influences cellular

process from growth, cell cycle, differentiation to growth arrest and process of

programmed cell death. And through adaptation and alteration, cells become more

capable of forming tumours. Initially, this procedure can be stopped by manipulating the

cells requirement for androgens although in the end it will just fail and cancer cells will

continue to grow. The terms 'androgen independent' and 'hormone refractory' may be

misnomers as the androgen receptor (AR) appears to maintain a role in cancer

progression as demonstrated by its continued and even increased expression. There

have been evidences that the prostate retains a level of androgen that is high enough to

induce AR transactivation in prostate cancer cell lines despite performing castration (both

surgical and medical).


The AR mutations and over-expression also enable transactivation to occur at low

levels of androgen as well as decreasing ligand specificity. The up regulation of co-

activators and possible down regulation of co-repressors further potentiate these effects.

Alternative pathways involving growth factors and receptors and IL-6 have been shown

to interact with the androgen signalling pathway enabling transactivation to occur even in

the absence of ligand (Girling, Mills, Neal & Whitaker, 2007).

Prevalence

Prevalence is the number of cases of a particular condition that exists in a given

population and consists of diagnosed cases plus those cases that are present but yet

undetected. Prostate cancer prevalence can be estimated from a variety of sources.

Prostate cancer is the fourth most common cancer in both sexes combined and the

second most common cancer in men.

The number of new cases of prostate cancer was 129.4 per 100,000 men per year.

The number of deaths was 20.7 per 100,000 men per year. These rates are age-adjusted

and based on 2009-2013 cases and deaths. Based on 2011-2013 data, approximately

12.9 percent of men will be diagnosed with prostate cancer at some point during their

lifetime. The prevalence of the prostate cancer in 2013 were an estimated 2, 850, 139

men living with prostate cancer in the United States.

In the past year, it is estimated that there will be 180,890 new cases of prostate

cancer and an estimated 26,120 people will die of this disease. The percentage of all new

cancer cases is 10.70% and percentage of all cancer deaths is 4.40%.


Signs and Symptoms

In most cases, prostate cancer symptoms are not apparent in the early stages of

the disease. The symptoms of prostate cancer may be different for each man and any

one of these may be caused by varying conditions. Consequently, it is vital for patients to

have routine screenings in the form of digital rectal exams (DRE) and prostate specific

androgen (PSA).

Since prostate gland is neighbouring the bladder and urethra, prostate cancer may

be accompanied by a variety of urinary symptoms. Depending on the size and location,

a tumour may press on and contract the urethra, preventing the flow of urine. Some

prostate cancer signs related to urination include:

Burning or pain during urination

Difficulty urinating, or trouble starting and stopping while urinating

More frequent urges to urinate at night

Loss of bladder control

Decreased flow or velocity of urine stream

Blood in urine (hematuria)

Other prostate cancer signs & symptoms

Prostate cancer may spread to nearby tissues or bones. If the cancer spreads to

the spine, it may press on the spinal nerves. Other prostate cancer symptoms include:

Blood in semen

Difficulty getting an erection (erectile dysfunction)

Painful ejaculation
Swelling in legs or pelvic area

Numbness or pain in the hips, legs or feet

Bone pain that doesn't go away, or leads to fractures

Prevention and Control

Different factors cause different types of cancer. Researchers continue to look into

what factors cause this type of cancer. Although there is no proven way to completely

prevent this disease, you may be able to lower your risk. Talk with your doctor for more

information about your personal risk of cancer as they have more knowledge about it.

High levels of testosterone, a male sex hormone, may speed up or cause the

development of prostate cancer. For instance, it is very uncommon for a man whose body

no longer makes testosterone to develop prostate cancer. In addition, stopping the bodys

production of testosterone, called androgen deprivation therapy (ADT), often shrinks a

prostate tumour.

A class of drugs called 5-alpha-reductase inhibitors (5-ARIs), which includes

dutasteride (Avodart) and finasteride (Proscar), may lower a mans risk of developing

prostate cancer. In clinical trials, both drugs have reduced the risk of prostate cancer.

Some previous studies suggested that 5-ARIs were linked to more aggressive prostate

cancers, but newer studies have shown this claim isnt true. Interestingly, according to

the results of a long-term follow-up study published in 2013, 78% of men taking finasteride

or a placebo were alive 15 years later. These results suggest that taking finasteride does

not decrease in the risk of death for men with prostate cancer. This subject remains

controversial, and the U.S. Food and Drug Administration (FDA) has not approved these
drugs for prostate cancer prevention. However, 5-ARI is FDA approved for the treatment

of lower urinary tract symptoms. Because the decision to take a 5-ARI is different for each

patient, any men considering taking this class of medications should discuss the benefits

and side effects with their doctor.

There is little information right now to prove the role of diet in preventing the risk of

having prostate cancer. Dietary changes may need to be made many years earlier in a

mans life to reduce the risk of developing prostate cancer. And here is a brief summary

of the current researches:

A diet high in fat, especially animal fat, may increase prostate cancer risk.

However, no prospective studies, meaning studies that look at men who follow either

high-fat or low-fat diets and then measure the total number of men in each group

diagnosed with prostate cancer, have yet shown that diets high in animal fat raise the risk

of prostate cancer.

A diet high in vegetables, fruits, and legumes, such as beans and peas, may

decrease the risk of prostate cancer. It is unclear which nutrients are directly responsible.

Although lycopene, the nutrient found in tomatoes and other vegetables, has been linked

to a lower risk of prostate cancer, the data so far have not demonstrated a relationship.

Currently no specific vitamins, minerals, or other supplements have conclusively

shown in clinical trials to prevent prostate cancer. Some, including vitamin D, vitamin E,

and selenium, may even be harmful for some men. Men should talk with their doctors

before taking any supplements to prevent prostate cancer.


Specific changes to diet may not stop or slow the development of prostate cancer,

and it is possible such changes would need to be made early in life to have an effect.

And lastly, there is no concrete evidence on how to prevent prostate cancer but a

healthy lifestyle may be important. The latest research suggests that being overweight or

obese probably increases your risk of aggressive or advanced prostate cancer. A

balanced diet and regular exercise can help you stay a healthy weight, so these may be

important for lowering your risk.


References

Adams, J. (1853). The case of scirrhous of the prostate gland with corresponding

affliction of the lymphatic glands in the lumbar region and in the pelvis. Lancet. 1,

393.

Lytton, B. (2001). Prostate cancer: a brief history and the discovery of hormonal ablation

treatment. J. Urol. 165, 18591862.

Young, H. H. (1905). Four cases of radical prostatectomy. Johns Hopkins Bull. 16, p. 315.

Walsh, P. C., Lepor, H. & Eggleston, J. C. Radical prostatectomy with preservation of

sexual function: anatomical and pathological considerations. Prostate. 4, 473485.

Huggins, C., Stephens, R. C. & Hodges, C. V. (1941). Studies on prostatic cancer: 2.

The effects of castration on advanced carcinoma of the prostate gland. Arch. Surg.

43, 209.

Schally, A. V., Kastin, A. J. & Arimura, A. (1971) Hypothalamic FSH and LH-regulating

hormone. Structure, physiology and clinical studies. Fertil. Steril. 22, 703721.

Whitmore, W. et al. (1972). Retropubic implantation of iodine-125 in the treatment of

prostate cancer. J. Urol. 108, 918920.

Girling, J. S., Whitaker, S. C., Mills, I. G., & Neal, D. E. (2007). Pathogenesis of prostate

cancer and hormone refractory prostate cancer. Indian Journal of Urology, 23(1),

35-42.

http://www.cancercenter.com/prostate-cancer/symptoms/

https://seer.cancer.gov/statfacts/html/prost.html
http://www.cancer.net/cancer-types/prostate-cancer/risk-factors-and-prevention

http://prostatecanceruk.org/prostate-information/are-you-at-risk/can-i-reduce-my-risk

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