Prostate Cancer Diagnosis & Treatment in Singapore

Surgery is a common treatment choice to curing prostate cancer. Patients in good health whose tumour has not spread outside the prostate gland may be treated with surgery to remove the tumour.

The main type of surgery for prostate cancer is radical prostatectomy. In this surgical procedure, the surgeon removes the entire prostate gland and some of the surrounding tissue, including the seminal vesicles. Removal of nearby lymph nodes may be done at the same time.

The main type of radical prostatectomy includes:

• Open radical prostatectomy: In this open operation, an incision or cut is made in the retropubic area (lower abdomen) or the perineum (the area between the anus and scrotum). Surgery is performed through the incision. If there are any reasonable chances that the cancer may have spread to nearby lymph nodes (based on a patient’s PSA level, prostate biopsy results and other factors), the surgeon may also remove some of these affected lymph nodes (known as a pelvic lymph node dissection). These nodes will be sent to the lab to check for cancer cells.
• Radical laparoscopic prostatectomy: Several small incisions or cuts are made in the wall of the abdomen. A laparoscope (a thin, tube-like instrument with a light and lens for viewing) is inserted through one opening to guide the surgery, while surgical instruments are inserted through the other openings to remove the prostate.

Robot-assisted laparoscopic radical prostatectomy: In this approach, also known as robotic prostatectomy, the laparoscopic surgery is done using a robotic system. Several small cuts are made in the wall of the patient’s abdomen. The surgeon inserts an instrument with a camera through one of the openings using robotic arms. The camera gives the surgeon a three-dimensional view of the prostate and the surrounding structures.

• Transurethral resection of the prostate (TURP): This operation is more often used to treat men with non-cancerous enlargement of the prostate called benign prostatic hyperplasia (BPH). It is also sometimes used in men with advanced prostate cancer to help relieve symptoms such as urinary blockage, however, it is not used to treat or cure the cancer. In this procedure, the surgeon inserts a narrow tube with a cutting device called a cystoscope into the urethra and then into the prostate to remove prostate tissue.

Radiation therapy is the use of high-energy rays to destroy cancer cells. A radiation therapy regimen, or schedule, usually consists of a specific number of treatments given over a set period of time.

Depending on the stage of the prostate cancer and other factors, radiation therapy may be used in the following situations:

• As the first treatment for cancer that is still just in the prostate gland and is low grade. The cure rates for men in these types of cancers are similar in men treated with radical prostatectomy.
• As part of the first treatment for cancers that have grown outside the prostate gland and in nearby tissues. The radiation therapy is done together with hormone therapy.
• Radiation therapy is used if the cancer is not removed completely or recurs (come back) around the prostate after surgery.
• If the cancer is advanced, radiation therapy is used to help keep the cancer under control and help keep prevent or relieve symptoms.

The different types of radiation therapy used are:

• External-beam radiation therapy: This is the most common type of radiation therapy treatment. Beams of radiation are focused on the prostate gland from a machine outside the body. This type of radiation can be used to try to cure earlier stage cancers, or to help relieve symptoms such as bone pain if the cancer has spread to a specific area of bone.

Another method of external-beam radiation therapy used to treat prostate cancer is called hypo fractionated radiation therapy. This is when a patient receives a higher daily dose of radiation therapy given over a shorter period, instead of lower doses given over a longer period. Extreme hypo fraction radiation therapy is when the entire treatment is delivered in five or fewer treatments. This is also called stereotactic body radiation therapy (SBRT) or stereotactic ablative radiation therapy (SABR).

• Brachytherapy: Brachytherapy, or internal radiation therapy, is the insertion of radioactive sources directly into the prostate. These sources, called seeds, gives off radiation just around the area where they are inserted and may be left for a short time (high-dose rate) or for a longer time (low-dose rate). Low dose rate seeds are left in the prostate permanently and work for up to one year after they are inserted. High-dose-rate brachytherapy is usually left in the body for less than 30 minutes, but it may need to be given more than once. Brachytherapy may be used with other treatments, such as external-beam radiation therapy and/or hormonal therapy.

• Three-dimensional conformal radiation therapy (3D-CRT): 3D-CRT is a radiation therapy that uses computers to precisely map the location of a patient’s prostate. Radiation beams will then be shaped and aimed at the prostate from several directions. This helps to make it less likely damage the surrounding normal tissues and organs.

• Intensity modulated radiation therapy (IMRT): IMRT is an advanced form of 3D-CRT therapy which is also the most common type of external beam radiation therapy for patients with prostate cancer. IMRT uses CT scans to form a 3D picture of the prostate before treatment. A computer uses this information about the size, shape, and location of the prostate cancer to determine how much radiation is needed to destroy it. With IMRT, high doses of radiation can be directed at the prostate without increasing the risk of damaging nearby organs.

• Proton therapy: Proton therapy, also called proton beam therapy, is a type of external-beam radiation therapy that uses protons rather than x-rays. At high energy, protons can destroy cancer cells. Unlike x-rays, which release energy both before and after they hit their target, protons cause little damage to tissue they pass through and release their energy only after traveling a certain distance. This means that proton beam radiation may deliver more radiation to the prostate while doing less damage to nearby normal tissues. Proton beam radiation can be aimed with techniques like 3D-CRT and IMRT.

Stereotactic body radiation therapy (SBRT): In SBRT technique, doctors uses advanced image guided techniques to deliver large doses of radiation to a precise area of the prostate. Due to the large doses of radiation in each dose, the entire course of treatment is given over just a few days.

Hormone therapy is a cancer treatment that removes hormones or blocks their action to stop cancer cells from growing. Because prostate cancer growth is driven by male sex hormones called androgens, lowering levels of these hormones can help slow the growth of the cancer. The most common androgen is testosterone. Hormonal therapy is used to lower testosterone levels in the body, either by surgically removing the testicles, known as surgical castration, or by taking drugs that turn off the function of the testicles, called medical castration. Which hormonal therapy is used is less important than the main goal of lowering testosterone levels. This treatment can be referred to with other names, including androgen-deprivation therapy (ADT).

Hormone therapy alone does not cure prostate cancer. Hormone therapy may be used in cases where:

• The cancer has spread too far to be cured by surgery or radiation
• If the cancer remains or recurs after treatment with surgery or radiation therapy
• Along with radiation therapy as an initial treatment, or if a patient is at a higher risk of the cancer recurring back after treatment, and/or growth of the cancer outside the prostate
• Before radiation to try to shrink the cancer to make the treatment more effective

The several types of hormone therapy can be used to treat prostate cancer are:

• Orchiectomy (surgical castration): Even though this is a type of surgery, its main effect is as a form of hormone therapy. In this operation, the surgeon removes the testicles, where most of the androgens (such as testosterone and DHT) are made. This causes most prostate cancers to stop growing or shrink for a time.

• LHRH Agonists: Luteinizing hormone-releasing hormone (LHRH) agonists, also called LHRH analogs or GnRH agonists, are drugs that lower the amount of testosterone made by the testicles. Treatment with these drugs is sometimes called medical castrationbecause they lower androgen levels just as well as orchiectomy. With these drugs, the testicles stay in place, however they will shrink over time. LHRH agonists are injected or placed as small implants under the skin. Depending on the drug used, they are given anywhere from once a month up to once every six months.
• LHRH Antagonists: This drug, also called a gonadotropin-releasing hormone (GnRH) antagonist, stops the testicles from producing testosterone like LHRH agonists. However, they reduce testosterone levels more quickly and do not cause the flare associated with LHRH agonists.Treatment with these drugs can also be considered a form of medical castration.
• Androgen receptor inhibitors: For most prostate cancer cells to grow, androgens must attach to a protein in the prostate cancer cell called an androgen receptor. Anti-androgens are drugs that also connect to these receptors, keeping the androgens from causing tumor growth. Anti-androgens are also sometimes called androgen receptor antagonists. These drugs are taken daily as pills but are not usually used on its own to treat the cancer. New generation of androgen receptor inhibitors that are more potent and efficacious are now available such as Enzalutamide, Apalutamide and Darolutamide.
• Novel hormonal agents such as Abiraterone Acetate which interrupts androgen production at testes, adrenal gland and cancer cell itself.

Immunotherapy, also called biologic therapy, is designed to boost the body’s natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function.

• Sipuleucel-T (Provenge): For some patients with castration-resistant metastatic prostate cancer who have no or very few cancer symptoms and generally have not had chemotherapy, vaccine therapy with Sipuleucel-T (Provenge) may be an option. Unlike traditional vaccines that helps boost the body’s immune system to help prevent infections, Sipuleucel-T (Provenge) boosts the immune system to help the body attack prostate cancer cells.

This vaccine is made specifically for each man and is used to treat advanced prostate cancer that is no longer responding to hormone therapy. To create the vaccine, white blood cells (cells of the immune system) are removed from the patient’s blood over a few hours while they are hooked up to a special machine. The cells are then sent to a lab, where they are mixed with a protein from prostate cancer cells called prostatic acid phosphatase (PAP). The white blood cells are then sent back to the doctor’s office or hospital, where they are given back to the patient by infusion into a vein (IV). This process is repeated two more times, two weeks apart, so that the patient gets three doses of cells. The cells help the patient’s other immune system cells attack the prostate cancer.

• PD-1 inhibitor: Another form of immunotherapy treatment is PD-1 inhibitor. Pembrolizumab (Keytruda) is a drug that targets PD-1, a checkpoint protein on immune system cells called T cells,that normally helps keep these cells from attacking normal cells in the body. By blocking PD-1, this drug boosts the immune response against prostate cancer cells. It has shown promising results in some men with prostate cancer and continues to be studied. This drug is given as an intravenous (IV) infusion every two or three weeks.

• PARP Inhibitor: Studies have shown that 20%–30% of men with metastatic prostate cancer have genetic alterations that impair cells’ DNA repair mechanisms. These mutations or alterations can be detected with genomic characterization of tumor and normal cells of the patient. 2 drugs- Olaparib and Rucaparib have been approved by the FDA for treatment of advanced metastatic castration resistant prostate cancer that have certain genetic alterations (BRCA 1 and 2, ATM and other DNA repair pathway genes)

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and may reach cancer cells throughout the body. This is also commonly termed as systemic chemotherapy.

Chemotherapy is used if the prostate cancer has spread outside the prostate gland, and when hormone therapy is not working. Chemotherapy is however not a standard treatment for early prostate cancer.

For prostate cancer, chemotherapy drugs are typically used one at a time. Some of the common chemotherapy drugs used to treat prostate cancer include:

• Docetaxel (Taxotere)
• Cabazitaxel (Jevtana)
• Mitoxantrone (Novantrone)

These drugs are typically given intravenously (IV) over a certain period of time. Often, a slightly larger and sturdier IV is required in the vein system to administer chemotherapy. They are known as central venous catheters (CVCs), central venous access devices (CVADs), or central lines. They are used to put medicines, blood products, nutrients, or fluids right into the patient’s blood. They can also be used to take out blood for testing.

Chemotherapy is given in cycles, with each period of treatment followed by a rest period to give the patient time to recover from the effects of the drugs. Cycles are most often two or three weeks long, and the schedule varies depending on the drugs used for the treatment.

Lutetium-177 PSMA therapy, also called Prostate-Specific Membrane Antigen Therapy, is a targeted treatment for men experiencing advanced prostate cancer with metastatic or treatment-resistant prostate tumors.

Lutetium-177 PSMA therapy allows for very specific and targeted radiation on prostate cancer cells, which is usually radiosensitive. The therapy aims to shrink the tumour and stabilise the disease. Patients whose bodies have not been responsive to other therapies or treatments may be referred to undergo this therapy.

The Lutetium-177 PSMA therapy combines therapy with diagnostics. The approach is referred to as ‘theranostic’. Most types of prostate cancers express high levels of PSMA. Rarely, about five to ten percent of prostate cancers do not create PSMA. Prior to starting Lutetium-177 PSMA therapy, a diagnostic scan will be performed to ensure that the therapy’s radiation will target the right areas during treatment.

PSMA is a type of protein expressed on the membrane of prostate cells, that is believed to have numerous cellular functions. Although the epithelium of the prostate naturally creates very low levels of PSMA, cancerous prostate tumours prostate extremely high levels (often 1,000 times higher than a normal prostate cell). If prostate cancer has spread to other areas of the body, the PSMA will be detectable in those areas. Lutetium is a radiation-based treatment that utilises a molecule to attach itself to the PSMA receptors located on the cancer cells. Lutetium-177 emits beta radiation that effectively damages cancer cells and, over time, destroys them. By targeting the molecules of PSMA, the radiation-focused treatment by Lutetium becomes very precise as the Lutetium molecule binds with the PSMA. The act of targeting the cancer cells is also often referred to as, ‘Peptide Receptor Radionuclide Therapy (PRRT).

Radiation therapy may cause side effects during treatment, including:

• Increased urinary urge or frequency
• Erectile dysfunction (impotence)
• Problems with bowel function, including diarrhea, rectal discomfort, or rectal bleeding
• Fatigue
• Lymphedema (swelling or pain in the legs or genital area)

Most of these side effects usually go away after treatment.

The possible side effects of hormone therapy may include:

• Reduced or absent sexual desire
• Erectile dysfunction (impotence)
• Shrinkage of testicles and penis
• Hot flashes, which may get better or go away with time
• Breast tenderness and growth of breast tissue (gynecomastia)
• Osteoporosis (bone thinning), which can lead to broken bones
• Anaemia (low red blood cell counts)
• Decreased mental sharpness
• Loss of muscle mass
• Weight gain
• Fatigue
• Increased cholesterol levels
• Depression

The common side effects from immunotherapy can include:

• Fever
• Chills
• Fatigue
• Back and joint pains
• Nausea
• Headache
• Skin rash
• Decreased appetite
• Constipation
• Diarrhea

The side effects of chemotherapy commonly include the following:

• Nausea and vomiting
• Diarrhea
• Constipation
• Tiredness
• Pain
• Loss of appetite
• Hair loss
• Skin and nail changes
• Numbness and tingling
• Swelling

The most common side effect is dry mouth and dry eyes. Occasionally, some patients may experience nausea or vomiting. Mild lethargy is also a side effect. Most of these side effects are transient and usually resolve after a few days. In patients with very extensive bone disease, marrow suppression is also a potential side effect due to collateral damage from the radiation on adjacent bone marrow.