Prostate Cancer
What is Prostate cancer?
Prostate cancer is cancer of the prostate gland (a small walnut-sized gland) in males. It secretes the seminal fluid which carries the sperm and nourishes the sperms produced in the testes. Prostate lies in the pelvis, encompasses the uretha and lies in front of the rectum. Prostate is a common cancer in men. usually prostate cancer grows and progresses slowly and remain confined in the prostate gland. However there are some cancer types that are aggressive and spread quickly. When detected early, the prognosis is good.
Causes of prostate cancer
The etiology of prostate cancer is unknown. Cancer in general begins when some cells in the prostate becomes abnormal. DNA mutations in the abnormal cells cause the cells to grow and divide more rapidly than normal cells do. The abnormal cells cumulatively form a tumor that can grow to invade nearby tissue (cancer). The cancer cells can break off and spread (metastasize) to other parts of the body.
Approximately 5%-10% of prostate cancers are due to inherited gene changes. There are several inherited genes that have been identified to cause an increase the risk of prostate cancer include: RNASEL, BRCA 1, and BRCA 2, DNA mismatch genes, and HoxB13.
Acquired gene mutations: Certain gene mutations happen during a person’s lifetime and are not passed on to their children. These changes are found only in cells that come from the original mutated cell. Most gene mutations related to prostate cancer seem to develop during a man’s life rather than having been inherited.
Risk factors of prostate cancer
Certain risk factors will predispose a person to prostate cancer and they are:
1. Age: the risk increases as you age. It is rare in men below 40. 60% of prostate cancer occur in men above 65 years old.
2. Race or ethnicity: African-American men and Jamaican men of African ancestry are diagnosed with prostate cancer more often than are men of other races and ethnic. Asian and Hispanic men are less likely to develop prostate cancer than are non-Hispanic white males.
3. Family history of prostate cancer: If a man's brother and brother have had prostate cancer, his risk may be increased.
4. Genetic factors: Certain inherited gene mutations increases the risk of prostate cancer. If he has a family history of genes that increase the risk of breast cancer (BRCA1 or BRCA2) or a very strong family history of breast cancer, then his risk of prostate cancer may be higher than others. Men with HNPCC (hereditary non-polyposis colorectal cancer) are also at risk of other cancers like prostate cancer. Other inherited genes associated with an increased risk of prostate cancer are: RNASEL, BRCA 2, DNA mismatch genes, and HoxB13.
5. Geographical location: Prostate cancer is most common in countries like North America, northwestern Europe, Australia, and on Caribbean islands. It is much less common in Asia, Africa, Central America, and South America.
6. Diet: Men who consume a lot of red meats and fatty foods and low amounts of fruits and vegetables have higher risk of developing prostate cancer.
7. Obesity: It is linked with higher risk of prostate cancer
8. Prostatitis: some studies find the chronic inflammation of prostate (prostatitis) has been linked with an increase risk of prostate cancer. But some studies did not find similar findings. Hence more research needs to be done to confirm this possible link.
Symptoms of prostate cancer
Early stages of prostate may not cause any signs or symptoms.
Advanced stages of prostate will cause symptoms like:
- Poor stream of urine
- Nocturia (increased urination frequency at night)
- Blood appears in urine/semen
- Erectile dysfunction
- Bone pain in hips, pelvis, lower back (may suggest cancer has spread to bone)
- Caudal equina (emergency): cancer has compressed the spinal cord causing urine and bowel incontinence as well as numbness and weakness in lower limbs
- Loss of weight
- Fatigue
Do note that certain conditions like prostatitis and benign prostate hypertrophy may also cause problems with urination.
Diagnosis of prostate cancer
Routine health screening for prostate cancer is controversial.
Tests for prostate cancer:
1. Digital Rectal Examination: During a medical physical examination, the doctor will put on glove and use lubricant to insert into the anus to examine for any lumps or hard mass of the prostate.
2. PSA Blood test: The Prostate Specific Antigen blood test measures the level of a protein found in the blood that is produced by the prostate gland and helps keep semen in liquid form. The normal level is usually less than 4 ng/mL, increasing levels of PSA indicates increasing likelihood of prostate cancer. However in <15% prostate cancers patients, their levels maybe in normal ranges. Men with a PSA level between 4 and 10 have about a 25% chance of having prostate cancer. If the PSA is more than 10, the chance of having prostate cancer is over 50%. Other causes of increased PSA levels are benign prostate hypertrophy (BPH), prostate infection and inflammation.
3. Transrectal ultrasound (TRUS): If the digital rectal examination and PSA level is suspicious of prostate cancer, then urologists will suggest for TRUS. A small ultrasound probe about the width of a finger size is inserted into the rectum and and scan is done to image the prostate gland to evaluate the prostate gland. TRUS is also used during therapy treatment of brachytherapy (internal radiation therapy) and cryotherapy).
4. Prostate biopsy: If suggestive of prostate cancer, then a biopsy is done during transrectal ultrasound. An anesthetic injection is given first before samples of prostate gland tissue is taken and examined under microscope to look for cancer cells. After biopsy, you may feel some soreness over the area, blood in urine and blood in semen for few days.
Grading of prostate cancer (Gleason Score): Prostate cancers are graded according to the Gleason system. Pathologists grade prostate cancers using numbers from 1 to 5 based on how much of the cells in the cancerous tissue look like normal prostate tissue under the microscope after a prostate biopsy tissue is done. Prostate cancers with lower Gleason scores (2 – 4) tend to be less aggressive, while prostate cancers with higher Gleason scores (7 – 10) tend to be more aggressive. Having any Gleason 5 in your biopsy or prostate puts you at a higher risk of recurrence.
5. More extensive imaging tests: To determine metastases of cancer (spread of prostate cancer to other parts of the body. Bone scan is to look for spread of cancers to the bone (often prostate cancer spread to the bones first). CT scans are not as useful as magnetic resonance imaging (MRI) for looking at the prostate gland itself. MRI scans compared with CT scan gives a clearer picture of the prostate and show if the cancer has spread outside the prostate into the seminal vesicles or other nearby structures. So CT scan , MRI and sometimes PET scan are used especially in advanced stages of prostate cancers to see the extension of spread of cancer to other organs/sites.
Stages of Prostate Cancer
Staging of prostate cancer is important as it plays a part in choosing the treatment options and predicts the prognosis of the patient.
According to the American Joint Committee on Cancer (AJCC) TNM system, the staging of prostate cancer is based on 5 key points:
Stage II. Cancer at this stage is still be small but the cancer cells maybe of aggressive type when viewed under the microscope. Or cancer in stage II may be larger in size than stage I and may have grown to involve both sides of the prostate gland but still confined to the prostate.
Stage III. The cancer has spread beyond the prostate to the seminal vesicles or other nearby tissues.
Stage IV. The cancer has grown to invade nearby organs, such as the bladder, or spread to lymph nodes, bones, lungs or other organs.
Treatment of prostate cancer
Depending on each individual case and the stage of prostate cancer, medical board comprising of urologists, medical oncologists and radiation oncologists will decide the treatment options. Besides medical treatment, psychological support from friends and family during the treatment process is also very important.
The various treatment options:
In men with very early prostate cancers, immediate treatments like surgery and chemotherapy may not be necessary and may bring more side effects. In some cases the cancer may progress very slowly and they may not need treatment at all. In such cases, the doctors may recommend active surveillance to monitor the situation. This comprise of regular follow ups with urologists, digital rectal examination, blood PSA levels test and possible biopsies to monitor the progression of the cancer. If the tests and follow up show your cancer is progressing, you may opt for other prostate cancer treatments such as surgery or radiation.
Surgery
The surgery to remove the prostate gland is called radical prostatectomy. Traditionally an incision was made below the navel to reach the prostate but this was replaced with laparoscopic method to reduce morbidity. Currently there is robot assisted laparoscopic surgery to minimize complications of operations because of better precision. Possible complications from operation is erectile dysfunction, urinary infections bleeding and urinary incontinence.
Radiation surgery
Radiation is used to kill prostate cancer cells. It can be delivered in two ways via external beam therapy (EBRT) or the placement of radioactive seeds into the prostate (prostate brachytherapy).
In external beam therapy (ERBT) , high-powered energy beams from a machine are directed at the prostate while you lie on the table. ERBT may cause fatigue and bladder and/or rectal irritation such that one may experience urination or stool frequency and blood in the urine or stools. These effects are usually temporary. Radiation also damage adjacent tissues resulting in skin irritation and local hair loss. Delayed onset of impotence can occur after radiation therapy.
In prostate brachytherapy, the radioactive seeds deliver a low dose of radiation over a long period of time. Similar to ERBT, one may experience urination and rectal irritation and blood in urine or stools.
Hormone therapy
Hormone therapy aims to reduce the testosterone hormone which is necessary for the prostate gland and the cancer cells to grow. In the past, this was accomplished by surgical castration which is called bilateral orchiectomy whereby bilateral testes are surgically removed. But in this new age, medication castration is carried out using oral medications to block the testosterone hormone instead.
Luteinizing hormone-releasing hormone (LH-RH) agonists block testosterone production by the testes whereas anti-androgens block the action of testosterone include the androgen receptor blockers. Medications and surgery result in low testosterone which cause fatigue, impotence, hot flushes, osteoporosis, reduced sex drive and possible weight gain.
Hormone therapy is used to treat men with advanced prostate cancer to shrink the cancer and slow the growth of cancer. In men with early stages of prostate cancer, hormone therapy may be used to shrink tumors before radiation therapy (neo-adjuvant therapy).
Chemotherapy
Chemotherapy involves injections or oral medications to kill the cancer cells. It is usually used for prostate cancer that has metastases (spread) and for cancer that does not respond to hormone therapy. New chemotherapy drugs have less side effects.
Cryotherapy
Cryotherapy involves freezing the prostate tissue to kill cancer cells.It is most frequently used as a salvage treatment after failure of radiation therapy. Under ultrasound guidance, small needles are inserted into the prostate gland. Through the needles a very cold gas is delivered to freeze the tissue followed by a second gas to reheat the tissue. This repeated freezing and thawing kill the cancer cells. The side effects include pain and the inability to urinate. Possible long-term side effects include tissue damage at needle-insertion sites, impotence, and incontinence.
Vaccine treatment (Immunotherapy)
Immunotherapy genetically engineered your own immune cells, injects them back into your body to help fight the cancer cells. This is used to treat advance recurrent prostate cancer or cancer that does not respond to hormone therapy. This type of treatment is expensive.
Bone directed treatment
Prostate cancer itself and hormone therapy will result in the bones being more brittle (osteoporosis). Bisphonates have been used for bone related treatment.
What is Prostate cancer?
Prostate cancer is cancer of the prostate gland (a small walnut-sized gland) in males. It secretes the seminal fluid which carries the sperm and nourishes the sperms produced in the testes. Prostate lies in the pelvis, encompasses the uretha and lies in front of the rectum. Prostate is a common cancer in men. usually prostate cancer grows and progresses slowly and remain confined in the prostate gland. However there are some cancer types that are aggressive and spread quickly. When detected early, the prognosis is good.
Causes of prostate cancer
The etiology of prostate cancer is unknown. Cancer in general begins when some cells in the prostate becomes abnormal. DNA mutations in the abnormal cells cause the cells to grow and divide more rapidly than normal cells do. The abnormal cells cumulatively form a tumor that can grow to invade nearby tissue (cancer). The cancer cells can break off and spread (metastasize) to other parts of the body.
Approximately 5%-10% of prostate cancers are due to inherited gene changes. There are several inherited genes that have been identified to cause an increase the risk of prostate cancer include: RNASEL, BRCA 1, and BRCA 2, DNA mismatch genes, and HoxB13.
Acquired gene mutations: Certain gene mutations happen during a person’s lifetime and are not passed on to their children. These changes are found only in cells that come from the original mutated cell. Most gene mutations related to prostate cancer seem to develop during a man’s life rather than having been inherited.
Risk factors of prostate cancer
Certain risk factors will predispose a person to prostate cancer and they are:
1. Age: the risk increases as you age. It is rare in men below 40. 60% of prostate cancer occur in men above 65 years old.
2. Race or ethnicity: African-American men and Jamaican men of African ancestry are diagnosed with prostate cancer more often than are men of other races and ethnic. Asian and Hispanic men are less likely to develop prostate cancer than are non-Hispanic white males.
3. Family history of prostate cancer: If a man's brother and brother have had prostate cancer, his risk may be increased.
4. Genetic factors: Certain inherited gene mutations increases the risk of prostate cancer. If he has a family history of genes that increase the risk of breast cancer (BRCA1 or BRCA2) or a very strong family history of breast cancer, then his risk of prostate cancer may be higher than others. Men with HNPCC (hereditary non-polyposis colorectal cancer) are also at risk of other cancers like prostate cancer. Other inherited genes associated with an increased risk of prostate cancer are: RNASEL, BRCA 2, DNA mismatch genes, and HoxB13.
5. Geographical location: Prostate cancer is most common in countries like North America, northwestern Europe, Australia, and on Caribbean islands. It is much less common in Asia, Africa, Central America, and South America.
6. Diet: Men who consume a lot of red meats and fatty foods and low amounts of fruits and vegetables have higher risk of developing prostate cancer.
7. Obesity: It is linked with higher risk of prostate cancer
8. Prostatitis: some studies find the chronic inflammation of prostate (prostatitis) has been linked with an increase risk of prostate cancer. But some studies did not find similar findings. Hence more research needs to be done to confirm this possible link.
Symptoms of prostate cancer
Early stages of prostate may not cause any signs or symptoms.
Advanced stages of prostate will cause symptoms like:
- Poor stream of urine
- Nocturia (increased urination frequency at night)
- Blood appears in urine/semen
- Erectile dysfunction
- Bone pain in hips, pelvis, lower back (may suggest cancer has spread to bone)
- Caudal equina (emergency): cancer has compressed the spinal cord causing urine and bowel incontinence as well as numbness and weakness in lower limbs
- Loss of weight
- Fatigue
Do note that certain conditions like prostatitis and benign prostate hypertrophy may also cause problems with urination.
Diagnosis of prostate cancer
Routine health screening for prostate cancer is controversial.
Tests for prostate cancer:
1. Digital Rectal Examination: During a medical physical examination, the doctor will put on glove and use lubricant to insert into the anus to examine for any lumps or hard mass of the prostate.
2. PSA Blood test: The Prostate Specific Antigen blood test measures the level of a protein found in the blood that is produced by the prostate gland and helps keep semen in liquid form. The normal level is usually less than 4 ng/mL, increasing levels of PSA indicates increasing likelihood of prostate cancer. However in <15% prostate cancers patients, their levels maybe in normal ranges. Men with a PSA level between 4 and 10 have about a 25% chance of having prostate cancer. If the PSA is more than 10, the chance of having prostate cancer is over 50%. Other causes of increased PSA levels are benign prostate hypertrophy (BPH), prostate infection and inflammation.
3. Transrectal ultrasound (TRUS): If the digital rectal examination and PSA level is suspicious of prostate cancer, then urologists will suggest for TRUS. A small ultrasound probe about the width of a finger size is inserted into the rectum and and scan is done to image the prostate gland to evaluate the prostate gland. TRUS is also used during therapy treatment of brachytherapy (internal radiation therapy) and cryotherapy).
4. Prostate biopsy: If suggestive of prostate cancer, then a biopsy is done during transrectal ultrasound. An anesthetic injection is given first before samples of prostate gland tissue is taken and examined under microscope to look for cancer cells. After biopsy, you may feel some soreness over the area, blood in urine and blood in semen for few days.
Grading of prostate cancer (Gleason Score): Prostate cancers are graded according to the Gleason system. Pathologists grade prostate cancers using numbers from 1 to 5 based on how much of the cells in the cancerous tissue look like normal prostate tissue under the microscope after a prostate biopsy tissue is done. Prostate cancers with lower Gleason scores (2 – 4) tend to be less aggressive, while prostate cancers with higher Gleason scores (7 – 10) tend to be more aggressive. Having any Gleason 5 in your biopsy or prostate puts you at a higher risk of recurrence.
5. More extensive imaging tests: To determine metastases of cancer (spread of prostate cancer to other parts of the body. Bone scan is to look for spread of cancers to the bone (often prostate cancer spread to the bones first). CT scans are not as useful as magnetic resonance imaging (MRI) for looking at the prostate gland itself. MRI scans compared with CT scan gives a clearer picture of the prostate and show if the cancer has spread outside the prostate into the seminal vesicles or other nearby structures. So CT scan , MRI and sometimes PET scan are used especially in advanced stages of prostate cancers to see the extension of spread of cancer to other organs/sites.
Stages of Prostate Cancer
Staging of prostate cancer is important as it plays a part in choosing the treatment options and predicts the prognosis of the patient.
According to the American Joint Committee on Cancer (AJCC) TNM system, the staging of prostate cancer is based on 5 key points:
- Tumor(T): the extent of the main (primary) cancer site
- Nodes (N) : Whether the cancer has spread to nearby lymph nodes
- Metastases (M): Whether the cancer has spread to other parts of the body
- The PSA blood level at the time of diagnosis
- The Gleason score, based on the prostate biopsy (or surgery tissue sample)
Stage II. Cancer at this stage is still be small but the cancer cells maybe of aggressive type when viewed under the microscope. Or cancer in stage II may be larger in size than stage I and may have grown to involve both sides of the prostate gland but still confined to the prostate.
Stage III. The cancer has spread beyond the prostate to the seminal vesicles or other nearby tissues.
Stage IV. The cancer has grown to invade nearby organs, such as the bladder, or spread to lymph nodes, bones, lungs or other organs.
Treatment of prostate cancer
Depending on each individual case and the stage of prostate cancer, medical board comprising of urologists, medical oncologists and radiation oncologists will decide the treatment options. Besides medical treatment, psychological support from friends and family during the treatment process is also very important.
The various treatment options:
- Observe with active surveillance
- Surgery
- Radiation therapy
- Hormone Therapy
- Chemotherapy
- Cryotherapy
- Vaccine treatment
- Bone directed treatment
In men with very early prostate cancers, immediate treatments like surgery and chemotherapy may not be necessary and may bring more side effects. In some cases the cancer may progress very slowly and they may not need treatment at all. In such cases, the doctors may recommend active surveillance to monitor the situation. This comprise of regular follow ups with urologists, digital rectal examination, blood PSA levels test and possible biopsies to monitor the progression of the cancer. If the tests and follow up show your cancer is progressing, you may opt for other prostate cancer treatments such as surgery or radiation.
Surgery
The surgery to remove the prostate gland is called radical prostatectomy. Traditionally an incision was made below the navel to reach the prostate but this was replaced with laparoscopic method to reduce morbidity. Currently there is robot assisted laparoscopic surgery to minimize complications of operations because of better precision. Possible complications from operation is erectile dysfunction, urinary infections bleeding and urinary incontinence.
Radiation surgery
Radiation is used to kill prostate cancer cells. It can be delivered in two ways via external beam therapy (EBRT) or the placement of radioactive seeds into the prostate (prostate brachytherapy).
In external beam therapy (ERBT) , high-powered energy beams from a machine are directed at the prostate while you lie on the table. ERBT may cause fatigue and bladder and/or rectal irritation such that one may experience urination or stool frequency and blood in the urine or stools. These effects are usually temporary. Radiation also damage adjacent tissues resulting in skin irritation and local hair loss. Delayed onset of impotence can occur after radiation therapy.
In prostate brachytherapy, the radioactive seeds deliver a low dose of radiation over a long period of time. Similar to ERBT, one may experience urination and rectal irritation and blood in urine or stools.
Hormone therapy
Hormone therapy aims to reduce the testosterone hormone which is necessary for the prostate gland and the cancer cells to grow. In the past, this was accomplished by surgical castration which is called bilateral orchiectomy whereby bilateral testes are surgically removed. But in this new age, medication castration is carried out using oral medications to block the testosterone hormone instead.
Luteinizing hormone-releasing hormone (LH-RH) agonists block testosterone production by the testes whereas anti-androgens block the action of testosterone include the androgen receptor blockers. Medications and surgery result in low testosterone which cause fatigue, impotence, hot flushes, osteoporosis, reduced sex drive and possible weight gain.
Hormone therapy is used to treat men with advanced prostate cancer to shrink the cancer and slow the growth of cancer. In men with early stages of prostate cancer, hormone therapy may be used to shrink tumors before radiation therapy (neo-adjuvant therapy).
Chemotherapy
Chemotherapy involves injections or oral medications to kill the cancer cells. It is usually used for prostate cancer that has metastases (spread) and for cancer that does not respond to hormone therapy. New chemotherapy drugs have less side effects.
Cryotherapy
Cryotherapy involves freezing the prostate tissue to kill cancer cells.It is most frequently used as a salvage treatment after failure of radiation therapy. Under ultrasound guidance, small needles are inserted into the prostate gland. Through the needles a very cold gas is delivered to freeze the tissue followed by a second gas to reheat the tissue. This repeated freezing and thawing kill the cancer cells. The side effects include pain and the inability to urinate. Possible long-term side effects include tissue damage at needle-insertion sites, impotence, and incontinence.
Vaccine treatment (Immunotherapy)
Immunotherapy genetically engineered your own immune cells, injects them back into your body to help fight the cancer cells. This is used to treat advance recurrent prostate cancer or cancer that does not respond to hormone therapy. This type of treatment is expensive.
Bone directed treatment
Prostate cancer itself and hormone therapy will result in the bones being more brittle (osteoporosis). Bisphonates have been used for bone related treatment.
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