Prostate cancer: Adenocarcinoma

• What is prostate cancer (adenocarcinoma of the prostate)?
• Statistics of prostate cancer
• Risk factors for prostate cancer
• Progression of prostate cancer
• Symptoms of prostate cancer
• Clinical examination of prostate cancer
• How is prostate cancer diagnosed?
• Prognosis of prostate cancer
• Treatment of prostate cancer
• References

What is prostate cancer (adenocarcinoma of the prostate)?

The prostate is a gland found only in men. It surrounds the urethra (the tube through the penis that drains urine from the bladder), and sits at the base of the bladder. The prostate is normally about the size of a walnut.
The function of the prostate is to produce fluid that forms part of the semen. This prostatic fluid, in addition to the fluid produced by the seminal vesicles, forms the fluid which carries the sperm when a man ejaculates.
An adenocarcinoma is a type of cancer that arises in the cells of glands. Most cells in the prostate gland are of the glandular type, which means that adenocarcinoma is the most common type of cancer to occur in the prostate. Cancer occurs when the genes of a cell become abnormal (mutation), causing the cell to multiply and interfere with the normal function of a tissue.
Once the cancer reaches a certain size, the abnormal cells can spread to other parts of the body and cause cancerous tumours to grow. This phenomenon is known as metastasis. If a tumour is capable of spreading to other parts of the body in this way, it is called malignant. Adenocarcinoma of the prostate is malignant, however many types grow extremely slowly, and so are unlikely to spread before a man dies of other causes.

Statistics of prostate cancer

Prostate cancer is the sixth most common cancer in the world and the most common form of cancer in Australian men (after nonmelanoma skin cancer) who have the highest incidence of this type of cancer in the world (105 cases per 100,000 males). One in six men will develop prostate cancer at some point in their lives. Although prostate cancer is the second most common cause of cancer in Indigenous Australian males (after lung cancer), the rates are lower in Indigenous men than in non-Indigenous men. It is not clear whether Indigenous Australians are truly less likely to develop prostate cancer, or whether lower rates of screening and diagnostic testing as well as a shorter life expectancy are contributing factors.
There has been a significant increase in the rates of diagnosed prostate cancer since screening asymptomatic men became popular in the 1990s. This screening is carried out via Prostate Specific Antigen (PSA) testing.
The mean age at the time of prostate cancer diagnosis is 68.4 years and 85% of new cases occur in men aged over 60. Following diagnosis, approximately 85% of men survive for 5 years or longer. Up to age 85, a quarter of Australian men will be diagnosed with prostate cancer and 1 in 25 will die from it.

Risk factors for prostate cancer

Age

The main risk factor for prostate cancer is age. Prostate cancer is rarely diagnosed before the age of 40. After 40, the incidence rises rapidly. PSA testing is not generally carried out on men aged under 50 unless they have significant risk factors. The rates of prostate cancer at different ages are as follows:

Age (years)	Percentage of men with prostate cancer
20–30	2–8%
31–40	9–31%
41–50	3–43%
51–60	5–46%
61–70	14–70%
71-80	31–83%
81–90	40–73%

Genetics

Around 5–10% of prostate cancer is due to genetic defects, so men who have a family history are more at risk of developing it themselves. Men who have a first degree relative (brother, father, son) who have had prostate cancer are two or three times more likely to develop prostate cancer themselves. This risk may be higher if the relative was diagnosed before the age of 60.
Identifying particular genes involved in prostate cancer has proved challenging. The BRCA1 and BRCA2 genes are associated with having a two to five times higher risk of prostate cancer.

Race

In American studies, Black men have higher rates of developing prostate cancer than White or Hispanic men. Indigenous Australians are at lower risk of being diagnosed with prostate cancer than White Australians.

Lifestyle

In Caucasians, smoking has been linked to a greater number of deaths due to prostate cancer.
Obesity may be linked with more aggressive forms of prostate cancer, but not with an increased incidence. The link between prostate cancer and diet has been extensively studied. Important findings include:

• A diet high in animal fat may contribute to prostate cancer;
• A diet low in vegetables may be a risk factor for prostate cancer; and
• Soy intake may have a modest protective effect against prostate cancer.

Other

Other men who are at increased risk of prostate cancer are those who have had high PSA levels, or abnormal prostate biopsies in the past.
In the past, testosterone levels were thought to be related to the development of prostate cancer, but this does not appear to be the case.

Progression of prostate cancer

In many cases, prostate cancer spreads so slowly that it never causes illness, and the patient will often die of other causes before the cancer can cause death. However, if the cancer is left untreated, it is possible that it will spread to local pelvic lymph nodes, and eventually spread to other parts of the body (metastasise). This may eventually result in organ failure and death. Bony metastases  from prostate cancer are common. For men who choose not to undergo definitive local treatment, their likelihood of survival relates to the aggressiveness of the prostate cancer.
Without treatment, the 10 year disease-specific survival of men with grade 1 prostate cancer (Gleason score 2 to 4) is 87%, with metastases present in 20%. Of men with grade 2 cancer, 42% develop metastases at 10 years. Ten year survival with grade 3 prostate cancer (Gleason 5 to 7) is 34% without treatment.
Another study found that 40% of men who did not have treatment for their prostate cancer died from the disease after fifteen years. About 80% of men who chose radical prostatectomy survived.

Symptoms of prostate cancer

Currently, most prostate cancers diagnosed have no symptoms. The cancer is detected due to abnormal PSA levels. In the past, prostate cancer was diagnosed due to an abnormal digital rectal examination (DRE), or due to the presence of urinary symptoms such as difficulty starting urine stream (hesitancy), urgent rush to get to the toilet (urgency), needing to pass urine frequently at night (nocturia), and dribbling of urine at the end of the stream (terminal dribbling). Remember, though, that these urinary symptoms are more commonly caused by benign prostatic hyperplasia (BPH) or by urinary tract infections.
Other symptoms that may raise suspicions of prostate cancer include new onset erectile dysfunction, blood in the urine (haematuria), blood in the semen (haematospermia), or symptoms of metastatic disease (e.g. bone pain).

Clinical examination of prostate cancer

The doctor will perform a digital rectal examination. This involves inserting a gloved finger into the rectum to feel the prostate and determine if it is enlarged or if there are any lumps. PSA and DRE are generally performed together to check for prostate cancer. PSA testing requires a blood test to be taken.

How is prostate cancer diagnosed?

A blood test is carried out to check the levels of prostate specific antigen (PSA). If a man’s PSA level is higher than 4 ng/mL, it may indicate that he is at increased risk of prostate cancer. However, most men with elevated PSA do not have prostate cancer.
If more investigation is needed, the next stage is usually a prostate biopsy, which is performed using ultrasound, via the rectum. A device is used to pass needles into the prostate, and withdraw them with tissue inside. The prostate tissue is examined under a microscope. If cancer is detected, it is given a Gleason score, which scores the cancer’s aggressiveness.
Serious complications due to prostate biopsy are rare. Hospitalisation (usually for urinary infections) or urinary retention occur in less than 1% of cases. One study found the following complication rates:

• These symptoms were generally short term.Blood in the semen (51%);
• Blood in the urine (23% longer than three days);
• Fever (3.5%); and
• Rectal bleeding (1.3%).

If cancer is identified on biopsy, the doctor will carry out further investigations, such as lymph node dissection or CT, to see if the cancer has spread.

Prognosis of prostate cancer

Due to PSA screening, prostate cancer is generally being diagnosed earlier, and in younger men. The risk of a man being diagnosed with prostate cancer at some point in his life is 1 in 6 (17%), and 3% of men die from prostate cancer. At autopsy, one third of men under the age of 80, and two thirds of men over the age of 80, are found to have prostate cancer. This data suggests that most men die with prostate cancer, rather than from it. At five years, 99% of men diagnosed with prostate cancer are still alive. At 10 years, 95% are still alive.
Determining the degree of spread of the cancer is known as ‘staging’. Cancer that is confined to the prostate gland is generally curable. The prognosis is not as good if the cancer has spread locally. If the cancer has spread to other parts of the body such as the bones, it is very difficult to cure. Treatment is focused on slowing the spread of the disease, and men may still live for many years with a good quality of life.
The prognosis is also related to the grade of the cancer, represented by the Gleason score, which is a measure of how aggressive the cancer is. 40% of men with Gleason scores of 8 to 10 are alive and disease free at 10 years. More than 90% of men with localised tumours and Gleason scores of 2 to 4 are alive at 5 years.

Treatment of prostate cancer

Treatment options for prostate cancer include:

• Active surveillance
• Local treatment
  • Radical prostatectomy
  • External beam radiotherapy
  • Brachytherapy (internal radiotherapy)
  • Hormonal therapy
• Palliative treatments

 Active surveillance

The risk of some small, non aggressive, localised prostate cancers ever spreading is very low. In these cases, the risks of treatment may outweigh the benefits. A doctor may therefore recommend ‘watchful waiting’, also known as ‘active surveillance‘.
In watchful waiting, the cancer and PSA levels are monitored, but no active treatment is carried out. This may be particularly appropriate for men who have a life expectancy of less than 10 or 15 years, due to advanced age or other medical problems.

Local treatment

If a man chooses to have treatment for prostate cancer, the main options in Australia include surgery, radiotherapy and hormone therapy. There is no good quality evidence that one approach is better than another, so treatment choice is based on the following considerations:

• Age, general medical condition and other medical problems. If a man has a life expectancy of less than 10 years, definitive treatment may not be recommended.
• Serum PSA and Gleason score
• Spread of the cancer
• Outcomes associated with treatment options
• Side effects and quality of life implications related to treatment options

Radical prostatectomy

Radical prostatectomy (RP) involves removing the prostate via a lower abdominal incision, or via keyhole surgery (laparoscopic). RP generally involves a 4–8 day hospital stay. A urinary catheter (tube through the penis into the bladder) with a urine bag attached remains in place for at least 2 weeks after the operation. Death rates due to radical prostatectomy are 0.5%, increasing to 1% in men over 75 years.
Sexual dysfunction may occur in 20–70% of patients following RP, and urinary problems in 15–50%. Bilateral nerve sparing surgery may be possible in some cases. In some cases, RP may be followed by radiotherapy.
See also Robotic Radical Prostatectomy.

Radiotherapy (External beam radiation therapy)

External beam radiation therapy (EBRT) may be used with RP or hormonal therapy to treat prostate cancer.
Beams of radiation (like x-rays) are targeted at the prostate by a machine that moves around the body. The rays kill the cancer cells. Small tattoos may be placed on the skin to make sure the beam is in exactly the right place, and minimise damage to healthy tissue.
This procedure is performed in an out-patient setting, and men are usually able to maintain their normal activities. Radiotherapy may lead to sexual dysfunction in 20–45% of cases, urinary incontinence in 2–16%, and bowel dysfunction in 6–25% of men who were previously normal in these areas.
For further information on EBRT, see Radiotherapy for Prostate Cancer.

Brachytherapy (internal radiotherapy)

There are two main types of brachytherapy:

1. Use of a radioactive pellet: This involves placing a small radioactive pellet into the prostate (seeding). The pellet loses its radioactivity over time, and is not removed. This option may be used for low Gleason score, low PSA, small, localised prostate cancer. Side effects such as painful urination, poor urine flow and bladder irritation are common, and can start a month after treatment; gradually getting better over 12 months.
2. Use of wide bore needles: This type of brachytherapy involves inserting wide bore needles into the prostate, through which radioactive sources can be given. After several days of treatment, the needles are removed. This type of brachytherapy is used in conjunction with EBRT for larger, more aggressive tumours. The needles may cause local discomfort, usually relieved by painkillers. Other side effects are similar to those for EBRT.

For further information on brachytherapy, see Radiotherapy for Prostate Cancer.

Hormonal therapy (androgen deprivation therapy)

Hormone therapy may be used in addition to EBRT. It is also used as palliative treatment (i.e. treatment for prostate cancer that cannot be cured). Hormone therapy does not improve outcomes when used before surgical treatment.
Testosterone appears to drive the growth of prostate cancer. Androgen deprivation therapy (ADT) aims to lower levels of testosterone. This may be achieved by removing the testes (often replaced with prosthetic testes) or medical castration with drugs.
Side effects of ADT include hot flushes, loss of libido, weight gain, erectile dysfunction, gynaecomastia, fluid retention, osteoporosis and mood swings.

Palliative treatments

Sometimes, prostate cancer is diagnosed and is too advanced to be cured by surgery or radiotherapy. In these cases, treatment is referred to as ‘palliative’. Palliative treatment is designed to relieve symptoms, maintain quality of life and, in many cases, prolong life. It will not cure the disease.

• Transuretheral resection of the prostate (TURP) may be carried out to relieve obstructive symptoms due to the cancer.
• Hormone therapy: ADT is a mainstay of treatment for cancer that is not resectable (removable by surgery). Eventually, the cancer will no longer respond to ADT.
• Bisphosphonates and analgesia may be used to treat cancer spread to bones.
• EBRT may be used to treat pain related to bone metastases.

Relative side effects of different treatments

• Radical prostatectomy and brachytherapy result in higher rates of urinary incontinence and sexual dysfunction than EBRT. Bilateral nerve sparing surgery (not possible in all cases) diminishes this difference.
• RT causes more bowel dysfunction than surgery.
• Brachytherapy causes more obstructive and irritative urinary symptoms.

Treatment recommendations

Good quality evidence of the best approach to prostate cancer is limited, but the following treatment strategies have been suggested:

• Low-risk disease: Radical prostatectomy, brachytherapy monotherapy, or EBRT.
• Intermediate-risk disease: EBRT or surgery. The role of brachytherapy alone is controversial. Brachytherapy plus EBRT may be superior to EBRT alone, though this is also controversial.
• High-risk disease: Radical prostatectomy with or without adjuvant EBRT, or EBRT plus ADT. EBRT or brachytherapy alone are not generally appropriate.

 

More information

For more information on prostate cancer, including diagnoses, types of treatments, and some useful tools, videos and animations, see Prostate Cancer.

 

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