Prostate Cancer

 Carol Yu, Ph.D

Introduction to prostate cancer

medical illustration of the effects of prostate cancer
Everything you need to know about Prostate Cancer and treatments

The second most common cancer and the fifth leading cause of death from cancer among men globally [1], prostate cancer affected approximately 1.1 million men worldwide in the year of 2012 (data from the Centers for Disease Control and Prevention). Most prostate cancers occur in men over the age of 50.

Prostate cancer is a tumour that starts in the cells of the prostate and can spread to other parts of the body, but most initially remains confined to the prostate gland. While most prostate cancers grow slowly, some can grow quite fast. Although less than 5% of men are diagnosed initially at late stages of prostate cancer, around 40% of these men continue on to find out that the cancer has spread [2]. Fortunately, if managed successfully, prostate cancer can be completely removed and cured.

The prostate is a walnut-sized gland below the bladder and just in front of the rectum.As a part of men’s reproductive system, it produces seminal fluid, which mixes with sperm produced from the testicles to make semen. When prostate cells are growing or behaving abnormally, they change in properties that can make them pre-cancerous. Often, these changes occur in the glandular cells of the prostate and there are a few types of prostate cancers including adenocarcinoma of the prostate, transitional cell carcinoma and sarcoma. More than 90% of prostate cancer cases are a type called acinar adenocarcinoma.

The diagnosis of prostate cancer is typically through biopsy. Just like any other cancers, early detection of prostate cancer before it spreads is the key to more successful treatment.

Symptoms of prostate cancer

At early stages of prostate cancer, symptoms are difficult to spot and there may not be any symptoms at all. However, there are some symptoms at later stages – the patient may feel tired, have difficulty urinating, frequent urination, have blood appearing in the urine, feel pelvic pain or back pain while urinating, feel pain when ejaculating, and feel pain or stiffness in the lower back, hips, or upper thighs. If you are experiencing these symptoms, consult your doctor as soon as possible for a screening test.

Risk factors for prostate cancer

A number of risk factors have been found associated with prostate cancer, including:

  • Increasing age (especially over the age of 65)
  • Certain ethnicity (men of African descent are more likely to get prostate cancer) (American Cancer Society)
  • Family history of prostate cancer[3]
  • Sexually transmitted diseases[4]
  • Inactivity [5]
  • Western diet consumption including increased fat consumption [6, 7]
  • High calcium intake[8]
  • Geography [9]

It is interesting to note that in some studies, sexual frequency or ejaculation frequency have been suggested to decrease the risk for developing prostate cancer[10]. However, there are also studies that show no significant correlations between the two [11]. The topic of association between sexual frequency or ejaculation frequency is still, therefore, controversial, and inconclusive.

Tests to screen for prostate cancer

There are available tests to screen for prostate cancer, although it remains controversial whether these tests are helpful in decreasing deaths from prostate cancer and whether screening increases the risks of over-diagnosis or over-treatment.

One of these tests is theprostate-specific antigen (PSA) test, which is a blood test that can detect specific abundance of certain genes in patients with prostate cancer. When high levels of PSA are found, doctors might suggest doing a biopsy.

Another test is the digital rectal exam, which involves the doctor feeling for a lump in the prostate with a gloved finger. Usually, nearby tissues will be taken for biopsy to test for prostate cancer.

Transrectal ultrasound, MRI, and CT scans are tests that utilize waves and X-rays to make pictures of the organ, in this case, the prostate, to detect presence of tumours.

If prostate cancer is diagnosed, a specialist will then determine the stage or grade of the tumour depending on its size, whether it has spread, and how far it has spread.

Stages of prostate cancer

Doctors may use the “TNM System”, where TNM stands for Tumour, Nodes, and Metastasis, to stage and categorize prostate cancer. Tumour describes the size of the original area of cancer, Nodes describes whether the prostate cancer has spread to nearby lymph nodes and to what extent it has spread, while Metastasis describes the spread of the prostate cancer to distant organs such as the bones.

Tumour staging:
T1 tumours are ones that are too small to be seen with scans or to be felt with prostate examinations. Usually, prostate cancer diagnosed at this stage is a result of noticing raised PSA levels from a blood test.

T2 tumours are ones that are growing inside the prostate gland only and have not spread. This stage is subdivided into 3 smaller groups – T2a, T2b, and T2c, according to how many lobes of the prostate gland is affected.

T3 tumours are ones that have broken through the covering of the prostate gland but have not yet spread into distant organs. This stage is further subdivided into T3a and T3b to more appropriately describe whether or not the cancer has spread into the seminal vesicles, or the glands that are responsible for the secretion of semen.

T4 tumours are ones that have spread to distant nearby organs such has the rectum and bladder.

Node staging:
If lymph nodes are described as “positive”, it means that the cancer cells have spread into the lymph nodes.
NX lymph nodes are ones that are either undetectable or cannot be checked.
N0 lymph nodes are ones with no cancer cells in it.
N1 lymph nodes are ones with presence of cancer cells.

Metastasis staging:
M0 means that the cancer is not yet spread outside the pelvic region.

M1 means that the cancer has already spread outside the pelvic region. This stage is further subdivided into M1a, M1b, and M1c to describe whether the cancer has spread to the nearby lymph nodes outside the pelvis, whether it has read into the bones, and whether it has spread to other distant places.

Another widespread system used to evaluate the prognosis of prostate cancer is the Gleason grading system, which uses a scoring system to evaluate the prostate cancer based on its microscopic appearance from a biopsy. A high Gleason score means that the prognosis of the prostate cancer is worse and it is more aggressive. The grading system goes from 2 to 10 with 10 being the most abnormalities in the prostate tissues tested. With any staging method, prostate cancer can commonly be staged into 4 broader stages:

Stage I: At this stage, the prostate cancer is found only in the prostate and the cancer is too small to be detected.

Stage II: The tumour can be detected at this stage, but has not spread beyond the prostate gland yet.

Stage III: The tumour has spread beyond the prostate gland but only involve nearby tissues.

Stage IV: The tumour has spread to distant tissues, into the lymph nodes, and distant organs such as the bones or liver.

How prostate cancer can spread to other parts of the body

Prostate cancer cells often grow locally within the prostate for a number of years before it extends into neighbouring tissues. Tumour cells can break off from its origin and into the bloodstream, allowing them to travel to distant parts of the body, settle there and start dividing into new tumours. The process of tumour migration is called metastasis. When that happens, the patient may also feel pain where the new tumour has settled. Besides the bloodstream, tumour cells can also travel through the lymphatic system, or the network of tubes that carry the liquid containing waste products and immune cells. These secondary tumours can therefore spread to almost anywhere in the body that blood and lymph can reach to, including the bones, the brain, and the lungs.

Prostate Cancer Treatment options

Similar to other cancer types, there are a few treatment options for those who have been diagnosed with prostate cancer, and we will discuss a few of them:
Surgery:
For patients with localized prostate cancer, meaning that the cancer has not spread, surgery can usually cure the prostate cancer. Usually the prostate cancer is at either Stage I or II. The standard procedure or operation is radical prostatectomy, or complete removal of the prostate gland. Removal of the prostate, however, can have major side effects, including impotence and urinary incontinence. Although doctors usually try to conserve the nerves near the prostate that govern erection, impotence can occur regardless. Therefore, it is important to discuss with your doctor whether surgery is a suitable choice for the patient.

Chemotherapy:
The use of cancer drugs to attack cancer cells and to stop their growth is called chemotherapy. However, these drugs may also attack normal and healthy cells that are not cancerous, which can lead to side effects, and will be discussed later.

Cryotherapy or Cryosurgery:
This method of treatment involves freezing the prostate cancer with very cold gases and is an option to treat early-stage prostate cancer. However, it is usually not used as a first line of treatment. Instead, doctors may use it for recurring prostate cancers. After the procedure, the patient may experience soreness and bruising in the treated area.

Hormonal therapy:
In patients with advanced prostate cancer, hormonal therapy by androgen deprivation is the main treatment. Since prostate cancer cells rely on these hormones to grow, lowering hormone levels can help control the growth of the cancer. Hormonal therapy therefore involves lowering levels of hormones such as androgen and testosterone. However, hormonal therapy does not cure prostate cancer. Some methods of hormonal therapy include surgical castration to remove the testicles, where most of the hormones are produced, or to use drugs to lower production of hormones or to stop them from working.

Radiation therapy:
This is mainly used in patients with localized prostate cancer that has not spread, and is also common in patients whose cancer has returned. Radiation therapy for prostate cancer utilizes high-energy rays or particles to kill cancer cells. There are different types of radiation therapy including brachytherapy, external beam radiation therapy, 3D conformal radiation therapy, intensity modulated radiation therapy, and proton beam radiation therapy. It is important to discuss with your doctor which radiation therapy method(s) is suitable for your needs.

Surveillance:
Patients who are diagnosed with low-risk prostate cancer are often times eligible for active surveillance, meaning that the patient and his doctor observe the progression of the tumour carefully over time. This type of treatment involves continuous observation of PSA levels, physical examinations, and repeated biopsies.

Vaccine therapy:
Using cancer vaccine, namely Sipuleucel-T (Provenge), this method boots the patient’s immune system to attack the prostate cancer cells in the body. This method is often used to treat advanced prostate cancer that is not responding to hormonal therapy. The vaccine is made specifically tailored to each patient by using his white blood cells, and has been shown to help extend the patient’s life by a few months [12].

Bone-directed treatment:
This type of treatment aims to maintain bone health in advanced prostate cancer patients. As prostate cancer spreads to the bone more frequently than any other cancers, maintaining bone health using bone-targeted therapies can provide benefits for those who have the cancer spread to the bone, or to prevent it to spread to the bone for others [13]. Bisphosphonates are drugs that are used to strengthen the bone.

After discussing about some treatment options, it is important to remember that the decision of treatment options depend both on the doctor, the patient and his personal needs. Often times, if it is diagnosed in an elderly man, especially in a low-grade form, treatment may not even be needed because the cancer usually grows slowly and the costs of treatment often times outweigh the benefits. Treatment options are typically based on factors such as age, health, and possible side effects of treatment.

I have been diagnosed with prostate cancer and will be going through treatment, what should I expect next?

Outcomes for prostate cancer heavily depend on the stage of the prostate cancer at diagnosis, the patient’s overall health, and his age. That being said, diagnosis at early stages of prostate cancer is associated with an excellent prognosis – close to 100% as a 5-year survival rate, which refers to the percentage of patients who will live for at least 5 years after initial diagnosis. When including all stages of prostate cancer, the relative 5-year survival rate is almost 100%, the relative 10-year survival rate is 99%, and the relative 15-year survival rate is 94%. Keep in mind, however, for prostate cancer patients that have the cancer spread to distant organs have a relative 5-year survival rate is only 28%.

Side effects from treatment and how can I manage them?

Much like any treatment in cancer patients, there are always side effects associated with them. We will discuss some of the side effects and possible ways that patients can manage them.

For ones that undergo radical prostatectomy as part of the surgery treatment option, there is a small risk of major side effects including adverse reactions to anaesthesia, heart attack, stroke, bleeding and blood clots. Very rarely, the intestines might be cut during the surgery, leading to abdominal infections. This may require subsequent surgeries to correct the problem. Overall, these surgical risks are dependent on the patient’s health, age, and the surgical skills of the surgeon. Common side effects of surgery include erectile dysfunction, impotence and urinary incontinence. However, patients may choose to use phosphodiesterase-5 inhibitors such as Viagra, Levitra, and Cialis that may help with erectile dysfunction but one should be aware that side effects of these drugs include headache, upset stomach, skin flushing or feeling warm, increased sensitivity to light, and stuffy nose. Other options such as vacuum devices and penile implants are also used to help solve erectile dysfunction issues.

Side effects of chemotherapy will be discussed in more detail in a later section, but common side effects include hair loss, mouth sores, nausea and vomiting, diarrhoea, loss of appetite, atypical bruising or bleeding, general fatique, and increased chances of infections.

For cryotherapy or cryosurgery, as already mentioned, patients may experience soreness and bruising in the treated area.

Due to changes in hormone levels, hormonal therapy are often associated with side effects such as decreased libido, or sexual desire, shrinkage of penis and/or testicles, erectile dysfunction, hot flashes, osteoporosis or bone thinning, low red blood cell counts, loss of muscle mass, fatigue, increased cholesterol, weight gain, reduced mental capacity, and even depression.

Patients who go through radiation therapy may experience fatigue that may prevail until a few months after treatment is finished. Some may experience bowel problems such as rectal pain, diarrhoea, and burning. Others may also experience urinary problems although they are usually not very severe. Patients might experience frequent urination. Patients undergoing radiation therapy may also experience erection problems.

For those who are going through the surveillance treatment option, physical side effects are most likely not involved because this treatment option does not use any external treatment sources such as chemo drugs or radiation. However, anxiety and distress may be the most common side effect [14] as patients are sometimes not entirely aware of the prostate cancer progression due to insufficient knowledge and may lack the opportunities to discuss their disease with their doctors. To alleviate anxiety and distress, patients are encouraged to seek support from local support groups, family, and friends.

Some commonly used drugs to treat prostate cancer

There are a few approved prostate cancer drugs out there in the market, and like other cancer drugs that treat other cancer types, doctors often give chemotherapy in cycles. Each cycle involves a treatment period followed by a recovery period so that the body can recover. Usually, a cycle lasts for a few weeks and in the case of prostate cancer, usually only one type of drug is used at a time. Schedules of drugs given and length of drug cycles depend on the particular drug(s) used, and should be well explained to you by your doctor.

Some of the more common prostate cancer drugs used will be presented below to identify their uses or benefits as well as their known side effects. You will find the common brand name of the particular drug in parenthesis.

Docetaxel (Taxotere):
These drugs work by interfering cell division of cancer cells. However, they may also affect the cell function of normal cells. Therefore, common side effects associated with the use of docetaxcel include hair loss and blood cell abnormalities.

Cabazitaxel (Jevtana):
These drugs are used to treat hormone-refractory prostate cancer, or advanced prostate cancer that is no longer responding to hormonal therapy. They work by stopping cancer cells from dividing, thus stopping cancer growth. Common side effects with the use of these drugs include increased susceptibility to an infection (immunosuppression), tiredness, breathlessness, unusual bruising, diarrhoea, constipation, loss of appetite, coughing, back pain, joint pain, and presence of blood in the urine.

Mitoxantrone (Novantrone):
Used in patients with advanced prostate cancer, mitoxantrone is typically used with prednisone (an anti-inflammatory agent) and they work by disrupting DNA synthesis in both cancer cells and normal cells. Common side effects of varying severity are associated with the use of these drugs. For example, one may experience nausea, vomiting, hair loss, heart damage, and immunosuppression.

Estramustine (Emcyt):
These drugs work by selectively stopping the cell growth of prostate cancer [15]. Common side effects associated with the use of these drugs include easy bruising, vomiting, insomnia, blood clots, itchiness and dry skin, impotence, leg cramps, nausea, diarrhoea, breast tenderness and enlargement, fluid retention, breathlessness, and weakness. Of note, estramustine has been withdrawn from a few markets including Australia, Brazil, Ireland, and Norway.

Doxorubicin (Adriamycin):
Also used in other types of cancer, these drugs target cancer cell growth by interfering with their DNA. The most serious adverse effects of using this drug are heart damage and inflammation of the bowel system, both of which can be life threatening. Other less serious side effects include hair loss, bone marrow suppression, nausea and vomiting, oral mucositis, esophagitis, diarrhoea, skin reactions, and local swelling where drug is administered.

Etoposide (Etopophos):
These drugs break cancer DNA strands, causing them to die [16]. They are also used to treat other cancers such as lung cancer leukemia. Side effects associated with the use of etoposide include hair loss, the feeling of pain where drug is administered, low blood pressure, constipation, diarrhoea, nausea, vomiting, allergic reactions, fever, and mouth sores.

Vinblastine (Velban):
Also used to treat other types of cancer, vinblastine works by inhibiting cancer cell division, thus stopping them from growing. Most patients who are treated with these drugs will experience some side effects, including constipation, loss of appetite, headache, weakness, bone marrow suppression, muscle cramps, and blister formation.

Paclitaxel (Taxol):
Used to treat other cancers such as breast cancer as well, these drugs interfere with cancer cell division, thus repressing tumour growth. Some of the common side effects for prostate cancer patients are allergic reactions, low red and/or white blood cell count, low platelet count, nausea, vomiting, fatigue, diarrhoea, mouth sores, irregular sperm production, hair loss, numbness or tingling in the hands or feet, muscle cramps, and brittle nails.

Carboplatin (Paraplatin):
The use of carboplatin, in combination with estramustine and paclitaxel, has been shown effective in treating patients with advanced prostate cancer [17]. Carboplatin on its own interferes with cancer cell DNA repair, thus interfering tumour growth. The use of these drugs is associated with a small number of side effects, although they still include bone marrow suppression, nausea and vomiting.

Vinorelbine (Navelbine):
Also used to treat other cancers, these drugs can be beneficial in treating patients with metastatic prostate cancer that do not respond to hormonal therapy [18]. It is moderate in terms of its toxic effects and these drugs are well tolerated in elder patients [19]. Still, some common side effects caused by the use of vinorelbine include nausea, vomiting, diarrhoea, mouth sores, hearing loss, weight loss, and loss of appetite.

Castrate-resistant prostate cancer

Patients with metastatic prostate cancer may commonly only see temporary benefits from hormonal therapy. Eventually, they may develop disease progression even when their hormone (androgen) levels are very low. Castrate-resistant prostate cancer refers to the ones where the tumour continues to grow even though hormone levels are as low as it could be as if the testicles were removed.

Historically, patients diagnosed with castrate-resistant prostate cancer have had rather poor survival rates. Until very recently, docetaxel was the only approved drug to treat castrate-resistant prostate cancer [20]. In the last few years, a number of new agents have been developed and have shown promising results with favourable toxicity. They include sipuleucel-T and cabazitaxel, which have already have outlined earlier. Recently, there have been a few experimental agents – MDV3100 and radium-223, both of which have demonstrated success in improving the overall survival in patients who no longer respond to their chemotherapy [2]. As a result of the significant medical advances, patients and physicians now have a few more options to target the castrate-resistant prostate cancer.

In castrate-resistant prostate cancer patients, hormonal therapy is typically still continued even though it may not respond as well, as the cancer could grow even more rapidly without hormonal therapy.

Radiation therapy may be an additional option to treat castrate-resistant prostate cancer to help relief bone pain if the cancer has already spread to the bone. In addition, bone-therapy can be used to strengthen the bone in addition to the standard treatments for castrate-resistant prostate cancer.

For patients diagnosed with castrate-resistant prostate cancer, it is important to openly discuss the available treatment options with your doctor, including their benefits, risks, overall goals, and costs.

Reference:

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