Prostate Cancer

Prostate cancer is the commonest cancer to affect males in the Western Hemisphere and Europe. Fortunately the incidence of prostate cancer is not that high in Malaysia, and is approximately one-fifth of that in the Western Hemisphere.

Prostate cancer in general is very slow growing, although the aggressive ones are known to spread fast within 3-5 years. When it is localized and confined to the prostate gland, it may not cause serious harm.

Currently until today, it is not possible to differentiate prostate cancers at diagnosis that can grow slowly from those that are aggressive.

Types of prostate cancer

The prostate has various functions, including:

    • producing the fluid that nourishes and transports sperm
    • secreting prostate specific antigen (PSA), a protein that helps semen retain its liquid state
    • helping aid urine control

It is not clear what causes prostate cancer. Prostate cancer starts when cells in the prostate become abnormal due to mutations in the abnormal cells’ DNA that causes the cells to grow and divide more rapidly and out of control compared to what normal cells do. The abnormal cells continue living and dividing, when other cells usually die to be replaced. The accumulating abnormal cells forms the tumor that can grow to invade nearby tissue. Some abnormal cells can also break off and spread (metastasize) to other parts of the body.

Almost all prostate cancers are adenocarcinomas. These cancers develop from the gland cells (the cells that make the prostate fluid that is added to the semen).

Other types of cancers that can arise from the prostate include:

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

These other types of prostate cancer are rare.

Some prostate cancers grow and spread quickly, but most grow slowly. In general, prostate cancers, unlike other cancers, have a long mean sojourn time, meaning the cancer cells divide slowly and spreads slowly. In fact, autopsy studies show that many older men (and even some younger men) who died of other causes also had prostate cancer that never affected them during their lives. In many cases, neither they nor their doctors even knew they had it.

For this, prostate cancer is considered the poster-boy example of a scrutiny-dependent cancer. Not all prostate cancers are fatal. But it is difficult to differentiate the ones that may be fatal from the ones that will not.

There are often no symptoms during the early stages of prostate cancer, but screening can detect changes that can indicate cancer.

Prostate cancer screening involves a rectal examination of the prostate and a blood test that measures levels of PSA in the blood. PSA is very specific to the prostate, but not necessarily cancer-specific. High levels of PSA suggest that cancer may be present. To confirm this, a prostate biopsy has to be done.

Risk factors for prostate cancer

Factors that may increase your risk of prostate cancer include:

  • Age. Your risk of prostate cancer increases as you age. The risk increases after the age of 50, but it is rare before the age of 45.
  • Race or ethnicity: It is more common in black males than white males. Asian and Hispanic males have a lower risk than black males or white males. In black men, prostate cancer is also more likely to be aggressive or advanced.
  • Family history and Genetic factors. If men in your family have had prostate cancer, your risk may be increased. Also, if you have a family history of genes that increase the risk of breast cancer (BRCA1 or BRCA2) or a very strong family history of breast cancer, your risk of prostate cancer may be higher. Men born with Lynch syndrome also have a higher risk of prostate and other cancers.
  • Obesity. Obese men diagnosed with prostate cancer may be more likely to have advanced disease that’s more difficult to treat.
  • Other possible factors. There is some evidence to suggest that other factors may play a role, but scientists need more evidence to confirm their involvement.  They include diet, smoking, exposure to chemicals, such as the herbicide Agent Orange, chronic inflammation of the prostate and persistent untreated sexually transmitted infections. Kindly note that there is still no evidence to prove these associations as causation of prostate cancer.

Prostate cancer screening

There are often no symptoms during the early stages of prostate cancer, but screening can detect changes that can indicate cancer.

Prostate cancer screening involves a rectal examination of the prostate and a blood test that measures levels of PSA in the blood. PSA is very specific to the prostate, but not necessarily cancer-specific. High levels of PSA suggest that cancer may be present. To confirm this, a prostate biopsy has to be done.

Prostate cancer screening is done by a combination of rectal examination of the prostate by the urologist, and a PSA blood test. A high PSA suggests possible prostate cancer.

Rectal examination of the prostate. Pic from Medscape

Controversies in prostate cancer screening

Prostate cancer screening is a very controversial issue.

Emerging evidence show that early detection may reduce the likelihood of dying from prostate cancer but this must be weighed against the serious risks incurred by early detection and subsequent treatment, particularly the risk of treating many men for screen-detected prostate cancer who would not have experienced ill effects from their disease if it had been left undetected. 

However the following should be noted:

  • Screening generally means general population screening unless stated otherwise (although selective screening is also considered screening).
  • Individual evaluation of a male with PSA and rectal examination of the prostate, after deciding the risk to benefit ratio, and after understanding the pros and cons of early detection, would be justified.

In other words, there is a difference between population or at-risk population screening which is usually done by national screening guidelines and public health authorities, from that of individual evaluation of a person based on their risk categories on the pros and cons of early detection of prostate cancer.

Debate continues regarding the risks and benefits of prostate cancer screening, and medical organizations differ on their recommendations.

Discuss prostate cancer screening with your doctor. Together, you can decide what’s best for you.

Concept 1: The normal PSA

Quite often there is a misinterpretation of what is the normal level of PSA. Usually in many lab tests, they usually inappropriately indicate the normal levels of PSA as 0-4 ng/ml. This is wrong and very misleading.

The normal PSA is the median PSA level in that particular age group of a male.

The normal or median PSA levels are:

40-49 years age: PSA 0.7 ng/ml

50-59 years age: PSA 0.9 ng/ml

60-69 years age: PSA 1.0-1.2 ng/ml

70-79 years age: PSA 1.5-5.0 ng/ml

If the PSA is at the median or less for the age group, then the risk for prostate cancer is very low. If a man’s PSA is higher than the median for his age group, his risk of having prostate cancer is higher and the risk that the cancer is aggressive is also higher.

Increasing PSA level increases risk of prostate cancer:

PSA Level (ng/ml)

Risk of prostate cancer (%)

0-0.5

0.6-1.0

1.1-2.0

2.1-3.0

3.1-4.0

0.0 – 6.6

6.0 – 13.0

12.0 – 17.0

17.0 – 23.9

21.0 – 26.9

It is important to understand this concept of what is the meant by the normal and median PSA.

This is because a trial by Lijla et al in 2007, Vickers et al in 2010, and studies reproduced by others showed that the mid-life PSA (PSA taken in the males in their mid-50 year’s age) predicted the risk of prostate cancer at 20-25 years later. PSA at age 60 years (above the median PSA value) predicts prostate cancer mortality by age 85 years.

A baseline PSA level between the median and 2.5 ng/mL is a significant predictor of future prostate cancer in 20 years, and was associated with a 14.6-fold and 7.6-fold increased risk of prostate cancer in men aged 40 to 49 and 50 to 59 years, respectively.

In other words, a single PSA taken in mid-50s age can predict ones’ risk of future prostate cancer.

If the PSA level is normal and at the median level, then the risk of prostate cancer in future is low.

If the PSA level is higher than the median level, then the risk of prostate cancer in future is higher, and these group of men will require regular PSA surveillance and follow up to detect future prostate cancer.

Concept 2: The PSA test is not a dichotomous test

One needs to understand what the PSA is all about.

The PSA is a continuous variable, and is not dichotomous. The value of doing a PSA is based on the fact that there is an increasing risk of prostate cancer with increasing PSA results. (In other words, the test does not indicate a positive or negative test. A higher PSA poses a higher risk of prostate cancer. This is not like a pregnancy test which will indicate a positive or negative test results).

There is no PSA level below which the risk of cancer is zero. There is no level of PSA which can confidently rule out a prostate cancer.

The higher the PSA level in the blood, the higher risk a person has prostate cancer.

Concept 3: The rising PSA and PSA dynamics

Once an initial PSA has been obtained (known as the initial PSA), the change in the PSA over time, known as the PSA velocity, plays a role in clinical decision making. It is felt that the PSA velocity over a year should be less than 0.75 ng/mL.

For example, a man 50 to 59 years of age with a PSA level that is 0.5 ng/mL one year and increases to 2.5 ng/mL the following year, although he may be viewed as having a normal PSA level, but the rate of change in his PSA (PSA velocity) would be worrisome and suggest an underlying prostate cancer.

Symptoms of prostate cancer

Early prostate cancer may not have any symptoms at all

Males who experience symptoms may notice:

  • difficulty starting and maintaining urination
  • decreased force in the stream of urine
  • a frequent urge to urinate, especially at night
  • acute urinary retention (unable to pass urine at all)
  • blood in the urine or semen
  • painful urination
  • in some cases, pain on ejaculation
  • Discomfort in the pelvic area
  • Bone pain

Advanced prostate cancer can involve the following symptoms:

  • bone fracture or bone pain, especially in the hips, thighs, or shoulders
  • swelling in the legs or feet
  • weight loss
  • tiredness
  • changes in bowel habits
  • persistent pelvic girdle or back pain

Diagnosis

The diagnosis of prostate cancer would start with a rectal examination and blood PSA levels to decide if prostate biopsy is necessary. During the rectal examination, the urologist will check manually for any abnormalities of the prostate with their finger.

There may be a necessity to do a uroflowmetry to assess the ability to pass urine and its flow, and ultrasound of the bladder and kidneys before and after uroflowmetry.

There will be a necessity to do a urine microscopy test.

Only a biopsy can confirm the presence and type of cancer. Prostate biopsy is the definitive method to confirm prostate cancer.

Prostate biopsy may either be done through the rectum, known as transrectal prostate biopsy, or transperineally.

Do note that such biopsies are random biopsies, meaning that early prostate cancers cannot be identified by imaging techniques.

Recently, studies have reported that multiparametric MRI (mpMRI) of the prostate may benefit in detecting the sites or areas to concentrate on during prostate biopsies. But do note that the current indications for mpMRI of the prostate is for individuals who had previous negative prostate biopsy reports and persistent elevated PSA test results.

It is best to discuss with the urologist on what is the best option for your when proceeding with prostate biopsy

Transrectal biopsy. An ultrasound probe is inserted into the rectum to show where the tumor is. Then a needle is inserted through the rectum into the prostate to remove tissue from the prostate. Pic from National Cancer Institute NCI

Staging of prostate cancer

The stage of the prostate cancer is based on the results of the staging and diagnostic tests, including the prostate-specific antigen (PSA) test and the Grade Group. The tissue samples removed during the biopsy are used to find out the Gleason score. The Gleason score ranges from 2 to 10 and describes how different the cancer cells look from normal cells under a microscope and how likely it is that the tumor will spread. The lower the number, the more cancer cells look like normal cells and are likely to grow and spread slowly.

The staging is based on the TNM staging classification and based on how large the tumor is, whether it has invaded outside the capsule of the prostate, whether it has involved the pelvic lymph nodes and seminal vesicles, and whether it has spread further to the bones, liver lungs and the rest of the body.

Localized prostate cancer – Pic from American Cancer Society

Pics from National Cancer Institute NCI

Treatment

Treatment will depend on the stage of the cancer, among other factors.

Making treatment decisions

As discussed earlier, in general, prostate cancer has a long mean sojourn time, ie most prostate cancers grow and spread slowly, but it is not possible to differentiate this from the potential aggressive ones. Some important things to consider include:

  • The stage and grade of your cancer
  • Your age and expected life span
  • Any other serious health conditions you have
  • Your feelings (and your doctor’s opinion) about the need to treat the cancer right away
  • The likelihood that treatment will cure your cancer (or help in some other way)
  • Your feelings about the possible side effects from each different treatment options that are discussed

The following are the various treatment modalities for prostate cancer. Do be informed that this is not a very exhaustive list, there are many more details on how prostate cancer is treated, and it would benefit if these issues are discussed with the doctor.

Early stage prostate cancer

If the cancer is small and localized, a doctor may recommend:

Watchful waiting or monitoring

The doctor may check PSA blood levels regularly but take no immediate action.

Prostate cancer grows slowly, and the risk of side effects may outweigh the need for immediate treatment.

Surgery

A urologist may carry out a radical prostatectomy. It involves removal of the prostate gland using either laparoscopic or open surgery. This may include removal of lymph nodes in the pelvic cavity.

Radical prostatectomy is a suitable and appropriate option for men with prostate cancers who are young and have a life expectancy of more than 10 years

Radiation therapy

Options include:

Brachytherapy:

A doctor will implant radioactive seeds into the prostate to deliver targeted radiation treatment. This is usually for smaller organ confined prostate cancers.

External Beam radiotherapy (EBRT):

Conformal radiation therapy. This targets a specific area, minimizing the risk to healthy tissue.

Another type, called intensity modulated radiation therapy (IMRT), uses beams with variable intensity.

There are different ways of doing this including conventional fractionation, moderate hypofractionation and extreme / ultra hypofractionation; with or without high dose rate brachytherapy. Your doctor can advise these options for you on discussions.

EBRT might be used for curative intent in localized prostate cancers or locally advanced prostate cancers. It may also be appropriate for palliating symptoms and for relieve.

EBRT may at times be combined with hormonal therapy as and when indications arises.

Advanced prostate cancer

As cancer grows, it can spread throughout the body. If it spreads, or if it comes back after remission, the treatment options will change.

Options include:

Hormonal therapy: Androgens are male hormones. The main androgens are testosterone and dihydrotestosterone. Blocking or reducing these hormones appears to stop or delay the growth of cancer cells. Various drugs can help to achieve this.

Another option is to undergo surgery to remove the testicles (if one is not keen to reduce testosterone levels by drugs only), which produce most of the body’s hormones.

Androgen receptor inhibitors: These are now available and can be used in advanced prostate cancers.

Chemotherapy: This is also effective for late stages of prostate cancer.

Bone targeted agents: They can strengthen bones which will invariably undergo osteoporosis not only due to cancer, but also due to hormonal therapy. Furthermore these agents may prevent the time to first fracture of the bones as well as any skeletal-related events.

Based on past statistics, the American Cancer Society expect the following percentages of people, on average, to survive for at least another 5 years after diagnosis:

Localized or regional cancer: Nearly 100% will survive at least another 5 years.

Distant: Around 30% will survive at least 5 more years if the cancer has affected other parts of the body.

With treatment, the overall 5 year survival rate for prostate cancer is 98%. Many people live longer than this, however.

The best way to detect prostate cancer in the early stages is to attend regular screening.

Prevention of prostate cancer

There is no evidence that you can reduce your risk of getting prostate cancer.

However, non-evidence based, you can try reducing your risk of prostate cancer if you:

  • Choose a healthy diet full of fruits and vegetables. Avoid high-fat foods and instead focus on choosing a variety of fruits, vegetables and whole grains. Fruits and vegetables contain many vitamins and nutrients that can contribute to your health.

Whether you can prevent prostate cancer through diet has yet to be conclusively proved. But eating a healthy diet with a variety of fruits and vegetables can improve your overall health.

  • Choose healthy foods over supplements. No studies have shown that supplements play a role in reducing your risk of prostate cancer. Instead, choose foods that are rich in vitamins and minerals so that you can maintain healthy levels of vitamins in your body.
  • Exercise most days of the week. Exercise improves your overall health, helps you maintain your weight and improves your mood. There is some evidence that men who don’t exercise have higher PSA levels, while men who exercise may have a lower risk of prostate cancer.

Try to exercise most days of the week. If you’re new to exercise, start slow and work your way up to more exercise time each day.

  • Maintain a healthy weight. If your current weight is healthy, work to maintain it by exercising most days of the week. If you need to lose weight, add more exercise and reduce the number of calories you eat each day. Ask your doctor for help creating a plan for healthy weight loss.
Remember: To be prostate healthy is to be heart healthy.

Talk to your doctor about increased risk of prostate cancer.

If you’re concerned about your risk of developing prostate cancer, talk with your doctor.

You can see your doctor anytime to discuss on prostate cancer screening when you are :

  • Age 50 for men who are at average risk of prostate cancer and are expected to live at least 10 more years.
  • Age 45 for men at high risk of developing prostate cancer. This includes men who have a first-degree relative (father or brother) diagnosed with prostate cancer at an early age (younger than age 65).
  • Age 40 for men at even higher risk (those with more than one first-degree relative who had prostate cancer at an early age).

Prostate cancer is rare below the age of 40 years,although it may still occur.

Men should make an informed decision with their doctor about whether to be screened for prostate cancer. The decision should be made after getting information about the pros and cons of screening.

Men should not be screened unless they have received this information.

If no risk of prostate cancer is found as a result of screening, the time between future screenings depends on the results of the PSA blood test:

  • Men who choose to be tested who have a PSA of less than 2.5 ng/mL may only need to be retested every 2 years.
  • Screening should be done yearly for men whose PSA level is 2.5 ng/mL or higher.

Recently there has been a strong endorsement by the 2019 Philadelphia Prostate Cancer Consensus Conference to perform genetic testing of all men with metastatic prostate cancer to inform precision medicine or clinical trial eligibility, as well as men with a family history suggesting hereditary prostate cancer, in addition to other cancers, such as breast, ovarian, pancreatic, and colon cancers, to inform active surveillance or screening discussions. Recommended priority genes for testing include BRCA2, BRCA1, and DNA mismatch repair genes in metastatic prostate cancer.

Prostate Cancer is a very broad topic with hundreds to thousands of studies and new understanding of the disease and treatment modalities. Prostate cancer deals with many issues that needs a broad understanding of the disease.

Currently until today, it is not possible to differentiate prostate cancers at diagnosis that can grow slowly from those that are aggressive.

It is best to discuss these issues on prostate cancer with your doctor to clarify any misconceptions and confusion that may arise on screening, diagnosis and treatment of prostate cancers.