· Prostate cancer is second most common cause of cancer death in men.
· Risk is greatest for men over 65, and if a father or brother had the disease.
· Early prostate cancer usually causes no symptoms.
· Treatment may include surgery, radiation or hormone therapy.
· Annual screening is recommended for men over 50, or over 45 if there is a positive family history.
· A lower intake of dietary fat and red meat may help prevent prostate cancer.
Prostate cancer is the second most common cause of cancer death in men, second only to lung cancer. It most commonly occurs in men above age 65, and very rarely occurs under the age of 40 years. It is a slow growing cancer, but progressive. If it is detected early and managed correctly, the survival rates are high.
The incidence of prostate cancer is rising, but the mortality rate of prostate cancer is decreasing. This paradox is most likely because of a more active prostate cancer screening, due to better media exposure and increased health awareness by males nowadays.
Because of routine screening for prostate cancer, it is diagnosed at an earlier stage, where it is still curable, hence the decline in mortality.
What is the prostate?
The prostate is a gland the size of an apricot positioned below the bladder outlet, with the urethra (the tube that carries urine from the bladder) traversing through it.
It forms part of the male reproductive system, secreting seminal fluid. This fluid acts as a nutrient rich transport medium for sperm, produced by the testes.
About 80% of the ejaculate volume is produced by the prostate. The prostate is under direct influence of the male hormone testosterone.
Cause of prostate cancer
The exact cause of prostate cancer is not clear. There are, however, a few risk factors for developing this disease. These include genetic factors (a positive family history), increase in age, and environmental factors such as diet.
Ten percent of prostate cancer is inherited. These cancers usually develop at a younger age and are more aggressive. If one first degree family member (father or brother) has prostate cancer, the risk for developing prostate cancer is twice as high as it is for the normal population. This increases to eleven-fold if three first degree family members have prostate cancer.
An increase in age also increases the risk of developing prostate cancer. Prostate cancer is exceedingly rare before the age of 40, but one in eight men between the ages of 60 and 80 years suffer from the disease. In very old men prostate cancer is not always clinically significant. Autopsy data indicate a 70% incidence of prostate cancer in 80-year-old men. The majority of these men died with rather than from prostate cancer.
Acquired risk factors from the environment mainly include diet. A typical Western diet high in animal fats and with a large consumption of red meat may increase the risk of developing prostate cancer.
It is important to note that early prostate cancer is usually completely asymptomatic. By the time that prostate cancer becomes bothersome or clinically apparent it has usually spread beyond the confines of the prostatic capsule and is no longer amenable to cure. In the first world early prostate cancer is usually diagnosed following screening. Prostate cancer can also be a chance finding in the tissue removed by transurethral resection for symptomatic benign prostatic hyperplasia (BPH).
The primary tumour can cause obstructive and irritative lower urinary tract symptoms similar to BPH.
Obstructive symptoms include poor stream, incomplete emptying and straining while passing urine. Irritative symptoms include frequent urination, urgency and nocturia (getting up to pass urine more than twice at night).
Prostate cancer can also cause blood in the urine and ejaculate, but this is not common.
In advanced prostate cancer the tumour cells can break loose, with typical spread (metastases) to the bony skeleton and the lymph glands of the pelvis. Bony metastases commonly involve the lower spine and pelvic girdle causing lower backache and hip pain. If these bone lesions are left untreated, they can lead to spinal fractures and paralysis. Lymphatic involvement can cause swelling of the legs and obstruction of the ureters (the tubes leading from the kidneys to the bladder), which can lead to renal failure.
Diagnosis of prostate cancer
Early and asymptomatic prostate cancer can be diagnosed by routine cancer screening. This involves a yearly PSA blood test and a digital rectal examination (DRE) in men above the age of 50, or 45 if there is a family history of prostate cancer. Routine screening is not advised for elderly men with a life expectancy of less than ten years, because this cancer is very slow growing. As mentioned before, they will probably die with the disease and not from it.
In clinically suspected or symptomatic men the same approach in diagnosis applies.
Prostate specific antigen (PSA) is a protein that is secreted by prostate cells. If the integrity of prostate cells is compromised (as with prostate cancer), the release of PSA into the bloodstream increases. The normal range of PSA is between 0 and 4 nanograms per millilitre. If the PSA count rises above 4, it raises suspicion of possible malignancy.
There are other causes for a raised PSA as well. Benign prostatic hypertrophy (BPH), prostatitis, injury to the prostate (prostate biopsy or catheterization) might also raise the PSA. Note, however, that cycling does not significantly raise PSA count.
The onus is on the urologist to decide when to react on a raised PSA, based on the clinical findings and associated symptoms, as well as the PSA density, the PSA velocity and PSA ratios.
Digital rectal examination
A digital rectal examination (DRE) is a method whereby the prostate is clinically assessed by inserting a gloved finger into the rectum. The urologist can palpate the prostate through the rectal to get an impression of the size and consistency of the gland. Suspicious and possible cancerous nodules in the prostate can also be detected.
If there are any suspicious nodules, a biopsy of the prostate should be done, regardless of the PSA count. It is important to state that a PSA blood test alone is not sufficient for prostate cancer screening, since up to 20% of prostate cancers might have a PSA below 4.
If there are abnormal findings with either the PSA or DRE, or both, a needle biopsy of the prostate is recommended. This procedure is done via a trans-rectal or trans-perineal route under ultrasound guidance. A trans-rectal ultrasound (TRUS) aids in the placement of the biopsy needles. This procedure is performed under local or general anaesthesia. It is normal to see blood in the urine, stool and ejaculate after this procedure, but this will resolve spontaneously.
The diagnosis of prostate cancer is confirmed by needle biopsy and histological analysis of the biopsy specimens.
Prostate cancer may also be an incidental finding when the histology is reviewed after a transurethral prostate resection (TURP) done for obstructive prostatic hypertrophy (BPH), where there was no clinical suggestion of cancer pre-operatively.
Doctor`s visit preparation
No specific preparation is needed for the first visit. The health professional will take a detailed medical history and perform a physical examination. The physical examination should include a digital rectal examination of the prostate gland. The health professional will almost certainly require a urine sample. It is a good idea not to empty the bladder shortly before the appointment. A blood sample will be taken to measure the level of PSA.
Staging and grading
Once the diagnosis of prostate cancer has been made, the disease has to be staged and graded. The stage refers to the extent and spread of the disease while the grade refers to the nature (aggressiveness) of the particular tumour. Staging and grading will determine the extent of disease and provide important prognostic information that will influence the management decisions.
Special investigations used to help with staging include PSA, X-ray of spine and pelvis, chest X-ray and a radionucleotide bone scan, if bone metastases are suspected.
TNM Staging system
Prostate cancer is staged with the TNM staging system. This classifies the extent of the cancer in the prostate (T-stage), the lymph nodes (N-stage) and whether distant metastatic spread is present or not (M-stage).
T-stage (extent of primary lesion)
· T1 – tumour confined to prostate, not palpable or visible on TRUS
· T2 – tumour palpable or visible on TRUS but confined to prostate
· T3 – spread beyond the prostatic capsule
· T3a – extracapsular spread only
· T3b – involvement of the seminal vesicles
· T4 – invasion into rectal wall, bladder neck or pelvic wall
N (Nodal) status
· N0 – regional nodes not involved
· N1 – regional nodes involved by tumour
M (Distant Metastases)
· M0 – no distant metastases
· M1 – distant metastases present
Grading refers to what the cancer looks like under a microscope. The most commonly used system is the Gleason grade and score. The glandular pattern is compared to that of a normal prostate and scored out of 5, where 1 resembles a pattern very close to normal and 5 resembles severely distorted glandular architecture. The two predominant glandular patterns within the cancer are graded out of 5 and the combined score calculated out of 10. The higher the Gleason score, the more aggressive the tumour and the worse the prognosis.
Patients with cancers confined to the prostate (T1 and T2) and no involvement of the lymph nodes or other organs (N0 and M0) are potentially curable by surgery or radiotherapy. Patients with disease beyond the prostate are not curable, but the cancer can still be treated to prevent progression.
Treatment of prostate cancer
Various options exist for the treatment of prostate cancer.
· Surgery (radical prostatectomy)
· Radiation (external beam radiation and brachytherapy).
· Hormonal treatment
· Watchful waiting.
The choice of treatment depends on the stage of the cancer as well as factors pertaining to each specific patient, such as life expectancy and co-morbid diseases. Surgery and radiation as treatment modalities are aimed at complete cure for prostate cancer, whereas hormonal treatment is merely to limit the progression of the disease. This is used when the cancer cannot be eradicated with surgery or radiotherapy.
Surgery for prostate cancer
Surgery for prostate cancer is called a radical prostatectomy. During this procedure the entire prostate and seminal vesicles are removed. The bladder is then re-connected to the urethra. The pelvic lymph nodes may also be removed for staging. The surgery can be done via the retropubic, perineal or laparoscopic method. A retropubic prostatectomy involves a 10 cm cut in the lower midline abdomen. With a perineal prostatectomy, the incision is made in the perineum, the area between the scrotum and the anus. With a laparoscopic prostatectomy, four small incisions are made in the abdomen through which the procedure is done.
Surgery is a treatment option only when the prostate cancer is still localized to the prostate gland (T1 – 2), no lymph node or metastatic spread is present (N0, M0), and life expectancy is more than 10 years. Due to the slow-growing nature of the disease, the benefit of cure usually only becomes apparent after 10 – 15 years. For this reason, a patient who receives treatment with curative intent should have a life expectancy of longer than ten
years. This prediction is made based on patient age and co-morbid diseases.
What to expect
A radical prostatectomy takes about two to four hours. Post-operatively there is a urinary catheter that stays in for 10-14 days. A wound drain stays in for two days. Patients are urged to mobilize from day two, and are usually discharged after about five days. The patient should expect to be booked off from work for at least four to six weeks.
The prostate and lymph nodes that have been removed will be sent for histological assessment to confirm whether all of the cancer has been removed, and whether the pelvic lymph nodes are involved or not.
The two main complications after surgery are impotence and incontinence. Although newer surgical techniques have dramatically reduced these complications, patients should be aware of the risk. The incidence of impotence is around 30% and incontinence about 4-10%. The erectile dysfunction can be treated with oral medication or penile injections at an early stage. Urinary incontinence is usually transient and will improve over a period of three to six months.
These complications and their management can be discussed with the urologist during the post-operative follow-up visits.
Radiotherapy for prostate cancer
Radiotherapy is a treatment method also with curative intent, whereby radiation energy is used to kill the cancer cells. This radiation can be delivered via external beam radio therapy (EBRT) or brachytherapy:
· EBRT stretches over a few weeks, during which daily sessions of radiation are delivered to the prostate.
· Brachytherapy, done under general anaesthesia, is a procedure that involves implanting radioactive seeds under ultrasound guidance into the prostate. Patients are discharged the same or next day after this relatively painless procedure. The advantage of brachytherapy over external radiation is that the radiation is delivered only to the prostate and not to adjacent organs like the bladder and rectum, limiting possible side-effects. The treatment also takes only one day, compared to multiple visits with EBRT. Brachytherapy with radioactive seeds has the lowest incidence of complications. The results of brachytherapy are comparable to surgery in patients with well-differentiated cancers and low PSA levels. This type of treatment however should not be used in patients with high-grade prostate cancer, or with obstructive urinary symptoms. Hormonal therapy is then sometimes used as well to improve the outcome of this treatment.
After treatment with curative intent, with either surgery or radiotherapy, the PSA should drop to an undetectable level. A PSA that fails to reach an undetectable level or rises after an initial drop indicates residual disease or metastases.
Hormone therapy is used in cases where the cancer has spread outside the prostatic capsule (T3-T4), or where there is lymph node involvement or metastatic spread. In other words, hormone therapy is used where the cancer is not curable by either surgery or radiotherapy.
Prostate cancer is dependent on the male hormone testosterone; 80% of patients will respond to hormonal treatment, which deprives the tumour of testosterone. This response usually involves shrinkage of metastases and symptomatic improvement for the patient, with a significant decline in PSA values.
The response to hormonal treatment is not a cure but can last for many years in some patients.
The two most common types of hormonal therapy that are used include:
· Surgical orchidectomy – surgical removal of the testes (castration), stopping testosterone production. Cessation of testosterone production with this procedure is permanent.
· Medical orchidectomy – three-monthly injections (LHRH analogues) that prevent the testes from producing testosterone. This can be given continuously on a three monthly basis or intermittently, based on the response of the cancer. Intermittent LHRH-analogue administration is called intermittent androgen deprivation (IAD).
The side effects of hormonal therapy (castration) include hot flushes (short-lived and transient), impotence and a decrease in sexual drive (libido), osteoporosis and weight gain.
This process involves surveillance of the diagnosed prostate cancer only, but no active treatment. Due to the slow-growing nature of the disease, the benefit of cure usually only becomes apparent after 10 – 15 years. It is a suitable option for patients with shorter than 10 years life expectancy and some patients with very early low-risk cancers.
The patient is informed about the decision to “sit back and wait” while monitoring the PSA. Only if a rise in PSA or increase in tumour stage warrants it, is treatment initiated.
Avoiding a high intake of dietary fat and red meat may be beneficial in preventing prostate cancer. Omega-3 fatty acid as contained in fish is a healthy substitute. Tomato-containing products rich in lycopene are also beneficial, as well as anti-oxidants found in selenium and vitamins E and D.
Screening for prostate cancer does not prevent the disease, but it ensures that the disease is detected when still curable. An annual screening for prostate cancer above the age of 50, or above the age of 45 if there is a positive family history, is recommended.
– Reviewed for Health24 by Dr Pieter Theron, Urologist, Netcare N1 City Hospital, Cape Town, August 2010