Prostate Cancer

In Hong Kong, prostate cancer was the fourth most common cancer and the third most common cancer in men. In 2022, there were 2,758 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 69.1% of newly diagnosed prostate cancer cases from 2012 to 2022. 

Prostate cancer was the fourth leading cause of male cancer deaths in Hong Kong. In 2022, a total of 519 men died from this cancer, accounting for 6.2% 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 the 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 abnormally. 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
• Computed tomography (CT) scan or positron emission tomography (PET)-CT scan
• Chest X-ray

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 respectively. The higher the grade, the more aggressive the cancer cells.
• Gleason score: The two grades will be added together to form 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 classification. Prostate-specific antigen (PSA) level and Grade Group are also considered when staging prostate cancer.

• 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 level is 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, bones, or other parts of the body.
• 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 localised prostate cancer grows slowly and almost never causes symptoms. The following are treatment options for low-risk localised prostate cancer.

Active surveillance

• If you have very-low-risk prostate cancer, your doctor may recommend active surveillance.
• Patients in the very-low-risk group have all the following criteria:
  • Stage 1c tumour
  • Grade 1
  • PSA < 10 ng/ml
  • Cancer just in 1-2 biopsy core with no more than half of each core showing cancer
• Active surveillance includes:
  • PSA test: once or twice a year, or as needed
  • Digital rectal examination: once a year, or as needed
  • Repeat MRI: every 1 to 2 years, or as needed
  • Repeat prostate biopsy: every 2-5 years, or as needed
• 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 open surgery or minimally invasive surgery with or without the assistance from a robotic device.
• 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 (luteinising hormone releasing hormone (LHRH) agonist or antagonist, 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, primarily produced by the testicles. The adrenal glands and prostate cancer cells can also produce androgens.
• 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. As a result, prostate cancer shrinks or grow more slowly for a time.

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. Luteinising 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 (known as chemical castration or medical castration).
• Administration: usually by injection under skin or into muscle once every one to six months
  • When the patient takes LHRH agonists for the first time, there may be a temporary rise in testosterone that lasts for about a week, 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.
• For example (trade names are in brackets): leuprorelin (Enantone), goserelin (Zoladex), triptorelin (Decapeptyl)

3. LHRH antagonists

• 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.
• Administration: monthly injection under skin
• For example: degarelix (trade name: Firmagon)

Prostate cancer that is controlled by maintaining low levels of testosterone, i.e. castration is known as “hormone-sensitive prostate cancer (HSPC)” or “castrationsensitive prostate cancer (CSPC)”. Castration can be attained with bilateral orchiectomy, LHRH agonists, or LHRH antagonists which are collectively known as “androgen deprivation therapy (ADT)”.

However, the cancer eventually learns how to survive at low levels of testosterone, which makes it unaffected by hormonal therapy. This is called “hormonal-resistant prostate cancer (HRPC)” or “castration-resistant prostate cancer (CRPC)”. 

4. Androgen receptor pathway inhibitors (ARPIs) / Anti-androgens / Androgen receptor antagonists

• ARPIs block the action of androgens. They attach to androgen receptors on prostate cancer cells and prevent them from using testosterone to grow.
• ARPIs are used in combination with ADT (i.e. orchiectomy or an LHRH agonist or antagonist) in at different stages of prostate cancer from recurrence after primary treatment to metastatic castration-resistant prostate cancer.
• First-generation ARPIs are given for a few weeks when an LHRH agonist is first started to help prevent tumour flare.
• Administration: orally once to thrice daily
• For examples (trade names are in brackets): 
  • First-generation ARPIs: flutamide, bicalutamide (Casodex)
  • Second-generation ARPIs: enzalutamide (Xtandi), apalutamide (Erleda), darolutamide (Nubeqa)

5. Androgen synthesis inhibitors

• 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.
• Abiraterone is used in combination with ADT (i.e. orchiectomy or an LHRH agonist or antagonist) in prostate cancers which are localised high-risk, locally advanced, and metastatic.
• Administration: orally once daily with low-dose prednisolone to avoid side effects
• For example: abiraterone acetate (trade name: Zytiga)

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 approaches:

Chemotherapy 

• For example (trade names in brackets): docetaxel (Taxotere), cabazitaxel (Jevtana), carboplatin, cisplatin, etoposide, mitoxantrone
• Chemotherapy is a systemic therapy administered through intravenous route, often in combination with a low-dose oral steroid drug. 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)
  • Increased chance of infections
  • Easy bruising or bleeding
  • Fatigue
  • Hair loss
  • Sore mouth and throat
  • Loss of appetite

Radioisotope therapy

1. Radium-223 

• Trade name: Xofigo
• Radium-223 delivers radioactive particles directly to damaged bones (like those containing cancer spread), giving off radiation that kills cancer cells. It is suitable for selected patients with bone metastases only. It helps relieve pain caused by bone metastases.
• Administration: via intravenous route once every four weeks for up to six doses
• Side effects: decrease in blood cell counts, which could increase risks for infections or bleeding

2. Lutetium Lu 177 vipivotide tetraxetan / 177Lu-PSMA-617

• Trade name: Pluvicto
• Lutetium Lu 177 vipivotide tetraxetan can be considered in metastatic castration-resistant prostate cancer patients who have already been treated with hormonal therapy and chemotherapy. The cancer cells must also have the prostate-specific membrane antigen (PSMA) protein, visualised under a PSMA PET scan.
• Administration: via intravenous route once every six weeks for up to six doses
• Side effects: feeling tired, dry mouth, nausea, loss of appetite, constipation, decrease in blood cell counts, which could increase risks for infections or bleeding

Treatments for painful bone metastases

1. External radiation therapy

• 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.

2. Radium-223

• Mentioned under “Radioisotope therapy”

3. Antiresorptive agents

• For example (trade names in backets): zoledronic acid (Zometa), denosumab (Xgeva, Prolia) 
• Antiresorptive agents help slow the growth of cancer that has spread to the bone and help delay or prevent fractures. They also help strengthening bones in men who are receiving hormonal therapy. 
• Side effects: flu-like symptoms, bone or joint pain, nausea, diarrhoea, feeling weak or tired 
• Rare but serious side effect: osteonecrosis of jaw 
• Administration: via intravenous route once every three or four weeks, or under the skin once every six months

4. Surgery

• Verteoplasty is a minor surgery to stabilise a painful collapsed bone in a spine weakened by prostate cancer. During this procedure, a small incision is made in the middle of the back, and a balloon is placed into the weak spinal bone. The balloon is first filled with air and then a cement-like mixture (which will harden) to stabilise the bone and spine.

Targeted therapy 

• For example: poly(ADP)-ribose polymerase (PARP) inhibitors like olaparib (Lynparza), talazoparib (Talzenna), niraparib (Zejula)
  • PARP inhibitors block the PARP proteins, making it very hard for tumour cells with an abnormal DNA repair gene to repair their damaged DNA, which often leads to death of these cells. Therefore, PARP inhibitors are only likely to be helpful if the cancer cells express mutations in one of the DNA repair genes i.e. homologous recombination repair (HRR)) genes, such as BRCA1 or BRCA2 genes
  • PARP inhibitors in combination with hormonal therapy (abiraterone or enzalutamide) can be considered for patients with metastatic castration-resistant prostate cancer (mCRPC) with DNA repair gene defects, such as BRCA1, BRCA2.
  • Common side effects include fatigue, nausea and vomiting, headaches, diarrhoea, decreased appetite, hair loss and low blood counts.
  • Administration: taken orally, once or twice daily

Immunotherapy

• For example: pembrolizumab (trade name: Keytruda) 
• Pembrolizumab can be used in mCRPC patients if the cancer cells have high level of microsatellite instability (MSI-H) or a defect in mismatch repair gene (dMMR) or high tumour mutational burden (TMB-H)
• Side effects: fatigue, cough, nausea, itching, skin rash, decreased appetite, constipation, joint pain, and diarrhea
• Less common serious side effects: infusion reactions (fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing), autoimmune reactions (problems in the lungs, intestines, liver, hormonemaking glands, kidneys, or other organs)
• Administration: given intravenously, once every three to six weeks

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

▶️ SUPPORT+ Easy Talk: Prostate Cancer (27.9.2024)

Hospital Authority Hong Kong Cancer Registry, 2022

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

Smart Patient (by Hospital Authority): Prostate cancer

Canadian Cancer Society: Prostate cancer

American Cancer Society: Prostate Cancer

Cancer Council: Prostate Cancer

FDA: Food and Drug Administration

Search Drugs Database. Drug Office, Department of Health, The Government of the Hong Kong Special Administrative Region

Macmillan Cancer Support: Prostate Cancer

NCCN Guidelines: Prostate Cancer. Version 1.2025

NCCN Guidelines for Patients: Advanced-Stage Prostate Cancer, 2024

NCCN Guidelines for Patients: Early-Stage Prostate Cancer, 2024

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 8th Jan,2025.