Prostate Cancer

In Hong Kong, prostate cancer was the third most common cancer in men. In 2021, there were 3,038 new cases of prostate cancer, accounting for 16.0% of new cancer cases in men in Hong Kong. Its median age at diagnosis was 71. The number of prostate cancer cases has grown rapidly in recent years, reflected by an increase of 84.8% of newly diagnosed prostate cancer cases from 2011 to 2021.

Prostate cancer was the fourth leading cause of male cancer deaths in Hong Kong. In 2021, a total of 518 men died from this cancer, accounting for 5.9% of male cancer deaths.

Prostate cancer usually develops slowly, without obvious clinical symptoms in the early stage. As a result, a lot of patients are diagnosed at advanced stage, affecting the treatment outcomes.

What is prostate cancer?

• The prostate is part of a man’s reproductive and urinary system. It is a walnut-sized gland below the bladder and in front of the rectum. It surrounds part of the urethra, which is the tube that carries urine and semen through the penis. 
• A male hormone called testosterone secreted by the testicles directly affects the growth and functions of the prostate gland.
• Cells in the prostate sometimes change and no longer grow, or behave normally. Changes to prostate cells can cause prostate cancer. 

Special attention should be paid if one falls within the following categories:

• Age: Being over 50
• Family history: Men with family history of prostate cancer
• Diet: Prolonged intake of food with high calories and fat
• Others: Smoking, obesity and prostate diseases, etc.

Symptoms and signs of prostate cancer may include:

• Frequent urination
• Weak or interrupted urine flow, or the need to strain to empty the bladder
• Frequent urge to urinate at night
• Blood in urine
• New onset of erectile dysfunction
• Pain or burning sensation while urinating (less common)
• Discomfort or pain when sitting, caused by an enlarged prostate

Other noncancerous conditions of the prostate, such as benign enlargement of prostate, can cause similar symptoms. Urinary symptoms also can be caused by an infection of the bladder or other conditions.

If cancer has spread outside of the prostate gland, symptoms may include:

• Pain in the back, hips, thighs, shoulders, or other bones
• Swelling or fluid buildup in legs or feet
• Unexplained weight loss
• Fatigue
• Change in bowel habits

• Digital rectal examination 
  • The doctor inserts a gloved finger into the patient’s rectum to check for any abnormal enlargement or hardening.
• Blood test: Prostate-specific antigen (PSA) test
  • The PSA test is used to measure the level of PSA in blood. PSA is a protein produced by the prostate. When the PSA level is higher than normal, it may indicate prostate cancer. For this reason, PSA is also a tumour marker.
  • PSA levels may also be high in men with non-cancerous conditions of the prostate, such as benign prostatic hyperplasia or prostatitis.
• Transrectal ultrasound (TRUS) and biopsy
  • A transrectal ultrasound (TRUS) uses an ultrasound probe placed in the rectum to make images of the prostate. It is used to:
    • guide a needle used for extracting tissue from the prostate during a biopsy
    • measure the size of the prostate
    • look for abnormal areas of the prostate
  • During a biopsy, the doctor removes tissues or cells from the body so they can be tested in a pathology lab. The report from the pathologist will confirm whether cancer cells are present in the sample.

Once the diagnosis of prostate cancer is confirmed, the following additional tests may be needed in some patients to determine if the cancer has spread:

• Magnetic resonance imaging (MRI)
• Bone scan
• CT scan or PET-CT scan

Adenocarcinomas are the most common type of prostate cancer. Almost all prostate cancers are adenocarcinomas. These cancers develop in the gland cells that line the prostate gland. 

Other types of cancer that can occur in the prostate include:

• Small cell carcinomas
• Neuroendocrine tumours (other than small cell carcinomas)
• Transitional cell carcinomas
• Squamous cell carcinomas
• Sarcomas

These other types of prostate cancers are rare.

Grading

The Gleason score is the most common system used to grade prostate cancer. The grade of a cancer indicates the aggressiveness and speed of growth of the cancer cells. This gives doctors an idea of the types of treatment to implement.

• Cancer grade: The pathologist looks at how the cancer cells are arranged in the prostate, and assigns a score on a scale of 3 to 5 from two different locations. The higher the grade, the more aggressive the cells.
• Gleason score: The two grades will be added together to create a Gleason score. This score tells doctors how likely the cancer is to grow and spread.

Prostate cancer is staged by the T, N, and M classifications. Staging also includes the Prostate-specific antigen (PSA) level and Grade Group.

• Stage I
  • The cancer is on one side of the prostate.
  • The cancer usually grows slowly.
  • PSA level may not be high, and the cancer may not be felt during a digital rectal examination.
  • There is no lymph node involvement nor metastasis.
  • Some cancers that can be felt during a digital rectal examination may still be classified as stage 1, if the Gleason score is 6 or below and the PSA is below 10.
• Stage II
  • Stage II prostate cancer is further classified into three subgroups: A, B or C.
    • Stage IIA: 
      • The cancer is on one or both sides of the prostate gland
      • The PSA blood test level is between 10 and 19
      • The Gleason score is 6 or below
    • Stage IIB: 
      • The cancer is on one or both sides
      • The PSA is below 20
      • The Gleason score is 7
    • Stage IIC: 
      • The cancer is on one or both sides
      • The PSA is below 20
      • The Gleason score is 7 to 8
• Stage III
  • Stage III indicates that the cancer is locally advanced. The tumour is growing, or the cancer has a high grade. PSA levels are high.
  • Stage III prostate cancer is further classified into three subgroups: A, B or C.
    • Stage IIIA: 
      • The cancer is on one or both sides of the prostate
      • The PSA is 20 or above
      • The Gleason score may be as high as 8
    • Stage IIIB: 
      • The cancer has spread outside the prostate gland to nearby tissues but not to the lymph nodes
      • The PSA may be any level
      • The Gleason score may be up to 8
    • Stage IIIC: 
      • This stage is similar to 3B, but the cancer may not be growing beyond the prostate
      • The Gleason score is 9 or 10
• Stage IV
  • Stage IV prostate cancer has spread beyond the prostate
  • Stage IV prostate cancer is further classified into two subgroups: A or B
    • Stage IVA: Cancer cells have spread to the regional lymph nodes
    • Stage IVB: Cancer cells have spread to distant lymph nodes, other parts of the body or to the bones.
• Recurrent
  • Recurrent prostate cancer is a type of prostate cancer that recurs after treatment. It may grow in the prostate area or in other parts of the body. If the cancer recurs, the doctor will conduct tests or scans that are similar to the original diagnosis to learn about the extent of the recurrence. 

When deciding which treatments to implement, factors below will be considered:

• The type and stage of the cancer
• The grade or Gleason score
• The possible side effects of treatments
• Patient’s personal preferences
• Patient’s overall health
• Patient’s age and life expectancy

Low-risk localized prostate cancer grows slowly and almost never causes symptoms. The following are treatment options for low-risk localised prostate cancer.

Active surveillance

• Treatments for prostate cancer can cause long-term side effects, so treatments are not given right away for very low-risk localised prostate cancer. 
• Active surveillance may be offered to men with prostate cancer with a very low risk of the cancer growing quickly or spreading.
• Active surveillance include:
  • PSA test every 3 to 6 months
  • Digital rectal examination at least once every year
  • Another prostate biopsy within 6 to 12 months, then a biopsy 2 to 5 years
• However, if the cancer starts to grow during active surveillance, other treatments may be needed.

Surgery (Radical Prostatectomy)

• The prostate and surrounding lymph nodes will be removed in surgery (prostatectomy). The resection can be done through conventional incisions or laparoscopic techniques, which are becoming popular. 
• After surgery, the patient may be at risk of urinary incontinence and impotence. 
• A radical prostatectomy may be offered if the patient is in good health and has a life expectancy of at least 10 years. 

Radiation therapy

• External beam radiation therapy may be offered instead of a radical prostatectomy. 
• Duration: 5 times a week over 4 to 7 weeks
• Radiotherapy may be preferred in men over the age of 70 who would have a higher risk of complications with surgery.
• In patients who has higher risks of recurrence, radiotherapy may be added after surgery to lower said risks.
• Common side effects:
  • Increased urinary urge or frequency
  • Problems with sexual function
  • Problems with bowel function, including diarrhoea, rectal discomfort or rectal bleeding
  • Fatigue
  • Most of these side effects usually disappear after treatment.

• Surgery (Radical prostatectomy) for selected patients
• Radiotherapy
• Hormonal therapy
  • Hormonal therapy (luteinizing hormone releasing hormone (LHRH) agonist or antagonist, or surgical removal of testicles (orchiectomy)). May be given before, during or after radiotherapy.

Hormonal therapy

• Prostate cancer cells use androgens to grow. An androgen is a type of hormone that controls the development of male physical traits, such as deep voices and growth of bodily hair. The most common androgen is testosterone. 
• Hormonal therapy is used to lower testosterone levels in the body, either by surgically removing the testicles, or by taking drugs that disable the functions of the testicles.

• Types of hormonal therapy include:

1. Bilateral orchiectomy

• Bilateral orchiectomy is the surgical removal of both testicles, which are the main source of testosterone production.
• The effects of this surgery are permanent and cannot be reversed. 

2. Luteinizing hormone-releasing hormone (LHRH) agonists

• LHRH (also called gonadotropin-releasing hormone, or GnRH) is produced by an area of the brain called the hypothalamus. This hormone stimulates the pituitary gland to produce luteinising hormone (LH), which in turn stimulates the testicles to produce testosterone.
• LHRH agonists (also called GnRH agonists) are drugs that cause the pituitary gland to produce extra LH. Eventually the pituitary gland stops responding to the LHRH agonist and the pituitary stops releasing LH. As a result, the testicles stop producing testosterone. The lowered amount of testosterone then slows the growth of prostate cancer cells.
• Administration: usually by injection under skin or into muscle
  • When the patient takes LHRH agonists for the first time, a temporary rise in testosterone that lasts for about a week may be caused, known as a tumour flare reaction. It may cause symptoms to worsen for a few weeks. The doctor will likely prescribe another type of hormonal therapy called an anti-androgen to help prevent a tumour flare reaction. Anti-androgens are usually started at the same time as LHRH agonists and are taken for a few weeks.
• LHRH antagonist
  • LHRH antagonists (also called GnRH antagonists) are drugs that stop the pituitary gland from producing LH. This causes the testicles to stop producing testosterone, which slows the growth of prostate cancer cells.
  • LHRH antagonists usually lower testosterone levels more quickly than LHRH agonists. They also do not cause a tumour flare reaction.

3. Androgen receptor (AR) inhibitors 

• For example: flutamide, bicalutamide, enzalutamide, apalutamide
  • Anti-androgens stop the production of androgens or block the action of androgens. They attach to androgen receptors on prostate cancer cells and prevent them from using testosterone to grow.

4. Androgen synthesis inhibitors

• For example: abiraterone acetate
  • Although the testicles produce most of the body's testosterone, other cells in the body can still make small amounts of the hormone that may drive cancer growth. These include the adrenal glands and some prostate cancer cells. Androgen synthesis inhibitors stop these cells from making testosterone.

Side effects of hormonal therapy include:

• Erectile dysfunction
• Loss of sexual desire
• Hot flashes with sweating
• Gynecomastia, which is growth of breast tissue that sometimes can lead to discomfort
• Depression
• Cognitive dysfunction and memory loss
• Heart problems and heart disease
• Weight gain
• Loss of muscle mass
• Osteopenia or osteoporosis, which is the thinning of bones

Other treatment methods include

Chemotherapy 

• For example: docetaxel, cabazitaxel
• Chemotherapy is usually a systemic therapy. This means that the drugs travel through the bloodstream to reach and destroy cancer cells all over the body, including those that may have broken away from the primary tumour in the prostate.
• Side effects of chemotherapy include:
  • Nausea and vomiting
  • Diarrhea 
  • Low blood cell counts (called bone marrow suppression)
  • Fatigue
  • Hair loss
  • Sore mouth and throat
  • Loss of appetite

Radioisotope therapy 

• For example: Radium 223
• This treatment delivers radiation particles directly to tumours, limiting damage to healthy tissues.  It is only suitable for selected patients.

Radiotherapy for the painful bone sites

• Can be used for relieving pain in cancer that spreads to the bones.
• Usually given in one to ten fractions.
• Some patients may experience increased pain after 4-5 fractions of radiotherapy but it usually subsides in one to two weeks.

Targeted therapy 

• For example: PARP inhibitors like olaparib
  • For patients with metastatic castration-resistant prostate cancer whose disease has continued to grow and spread during treatment with abiraterone and/or enzalutamide, and those with DNA-repair gene defects, such as BRCA1, BRCA2, and several others, a PARP inhibitor may be considered.
  • Common side effects include fatigue, nausea and vomiting, headaches, diarrhoea, decreased appetite, hair loss and lower levels of certain blood cells.

To prevent prostate cancer, maintaining a healthy lifestyle and eating habits are essential.

• Limiting the intake of animal fat and meat (especially red meat)
• Consuming more beans and its products 
• Having a greater proportion of fresh vegetables and fruits in the diet

Hong Kong Cancer Registry, 2020, Prostate cancer

The Hong Kong Anti-Cancer Society: Prostate cancer (Chinese only)

Smart Patient (by Hospital Authority): Prostate cancer

American Society of Clinical Oncology (ASCO): Prostate cancer

Canadian Cancer Society: Prostate cancer

Special thanks to Mr. Joshua Tang, Mr. Matthew Ho-Fan Cheng (Class M23), medical student of Li Ka Shing Faculty of Medicine, the University of Hong Kong, and Dr. Steven Wai-Kwan Siu, Department of Clinical Oncology, Queen Mary Hospital for authoring and editing this article.

Last updated on 18th Dec, 2023.