OVERVIEW OF PROSTATE CANCER

The prostate gland is a small organ found below the bladder of the male reproductive system. It surrounds a part of the urethra called the prostatic urethra. About the size of a walnut, It is an accessory glandular organ which secretes the whitish prostatic fluid which is one of the main components of human semen.

Cancer of the prostate gland is one of the most common cancers in middle aged men. It normally affects men above 65 years.The cancer cells may grow slowly initially or even rapidly depending on the type. Cancers of the prostate are normally Adenocarcinomas(cancers of glandular epithelial cells; cells that line the surfaces of glands.)

WHAT IS PROSTATE CANCER?

This happens when cells in the prostate grow abnormally and spread to other organs .This abnormal growth of cells normally begins in the peripheral zone of the prostate gland. This zone is at the posterior part of the gland and it is made up of large amounts of glandular tissues.

TYPES OF PROSTATE CANCER?

For effective management of prostate cancer it is important to know the types. These types may be fast growing (aggressive) or slow growing(non-aggressive). The type of cancer is mostly based on the original cell the cancer begins from.

  • Acinar Adenocarcinoma:

The malignant glandular epithelial cells of the prostate grow into saclike structures called acinus. The epithelial cells in this cancer are either cuboidal or columnar in shape  .This is the most common type of prostate cancers known.

  • Ductal Adenocarcinoma :

The cancer cells originate from the cells lining the ducts of the gland.The growth rate and metastasis is higher than the acinus adenocarcinoma.

  • Transitional Cell Carcinoma:

The cancerous cells in this type arise from the transitional epithelial cells. The cancer mostly begins from the bladder and invades the prostate. Although rare, the cancer may begin from the prostate and spread to the urethra and bladder.

  • Squamous cell  Carcinoma of prostate :

The cancer cells originate from the squamous epithelial cells covering the prostate gland. These cells grow quicker and spread faster .They are more aggressive than the adenocarcinomas.

  • Small Cell Carcinoma of the prostate:

The cells in this type of cancer are undifferentiated cells (have not taken a final form) and are highly malignant .The cells are small and have little to no cytoplasm .These cells contain small secretory granules which produce hormones .

This type of cancer is  also known as neuroendocrine cancer. This mean that the cells in this cancer have influence from the nervous system, which stimulates them to produce hormones. This cancer type is not very common.

  • Other rare types of prostate cancers may occur. Examples include carcinoid and sarcoma variants.

PRECANCEROUS NEOPLASMS OF THE PROSTATE GLAND

These conditions are normally asymptomatic and are only detected during prostate biopsy. In this scenario, there are abnormal cellular changes in the cells of the prostate gland. The changes in the cells are mostly mild with no metastasis, but these cells are concidered precancerous because they can become cancerous if not treated in time. Examples of these precancerous conditions are discussed below . 

  • Prostatic intraepithelial neoplasia (PIN):

During prostate biopsy, abnormal cells are detected on the microscope.The abnormal cells don’t appear invasive or metastatic. It can be called Carcinoma in situ of the prostate. This is grouped into two, based on the extent of deviation of the prostate cells from their normal structure, towards abnormal.

The first type of cells look nearly normal  (Low grade PIN) and the other type of cells appear more abnormal from the normal prostate cells (High grade PIN ). 

  • Proliferative Inflammatory (PIA):

The abnormal cells are mostly due to epithelial regeneration, as a result of inflammatory reactions. The cells look smaller than normal cells and can lead to high grade prostatic intraepithelial neoplasia .

EPIDEMIOLOGY

Prostate cancer is the most common cancer in men, after skin cancer. It affects men above the age 65 with an average of 66 years. African-American men are more likely to present with prostate cancer than Asians. According to the American Cancer Society’s statistical findings in 2018, the estimated number of newly diagnosed prostate cancer cases in USA was 164,690 and about 29,430 deaths were recorded due to prostate cancer in 2018.

Prostate cancer kills more men in USA, after lung cancer which ranks as the most common cause of cancer death. About 1 out of 41 men diagnosed with prostate cancer will die from the condition. Though prostate  cancer can be a serious condition, only a small number of those diagnosed die from it .

CANCER RESEARCH BUDGET PER YEAR

Most governments of developed countries allocate funds for cancer research. This helps to boost the effective management of various cancerous conditions in the world.The US government normally gives funds to the National Cancer Institute for research into new cancer drugs and management procedures.

According to the National Cancer Institute, the budget allocation for prostate cancer research, made from 2012 to 2017, is about  1442.1 billion dollars.The average amount per year spent on prostate cancer research within this time is estimated at around  250.0million dollars.

In addition, other non-governmental organizations generate funds to help research into prostate cancer programs. Some health related companies and even charitable donations from the general public, are some of the key sources of financing cancer research.

CAUSES

Although the exact cause of prostatic malignancy is not clear, it is known that mutations on genes that regulate cell growth in the prostate cause this disease. These mutation may be:

  • Spontaneous mutations:

Inherited genetic mutations or acquired in intrauterine (in the uterus) life .These mutations are congenital (present at birth) .

  • Induced mutations:

Acquired mutations which occur after birth, as a result of environmental factors .

PATHOPHYSIOLOGY

The mutations of genes found in the prostate gland cells, lead to the abnormal growth of the cells. Most of the abnormal cells are epithelial in origin and they form precancerous lesions. This is called carcinoma in situ. These cells are localized and stay in their place of origin.

The precancerous lesions continue to grow bigger and invade neighboring tissues and organs. The abnormal cells grow and begin to spread through lymphatic vessels and blood to distant organs. The ability of the cells to invade or spread is what makes them cancerous.

RISK FACTORS

Prostate cancer can occur in all men. Nevertheless, these factors make its occurrence more likely.

  • Old age:

Increasing age corresponds directly with risk of getting prostate cancer .

  • Family history of prostate cancer:

If there are males diagnosed of Prostate cancer in your family .

  • Obesity:

There is a link between unhealthy lifestyles, being overweight and prostate cancer

  • Known Genetic changes:

Mutations in tumor suppressor genes BRCA1 /BRCA2.

SIGNS AND SYMPTOMS

Prostate cancer in its early stages may not show any clear clinical manifestations; if they do however, the early signs are urine related symptoms .

  • Difficult urination .
  • Reduced force in the stream of urine.
  • Blood in urine .
  • Blood in semen
  • Erectile dysfunction.
  • Pain in the pelvic region and back .
  • Numbness in the pelvic region and back.

PROGNOSIS

The outcome of prostate cancer is not always death. Early detection by prostate biopsy can help reduce the deaths of prostate cancer patients.

Prostate cancers which are non-metastatic at the time of  diagnosis have 5 year patient survival rate of 100%. Metastatic cancers have 5 year survival rate of 29%.

There are clear markers of outcome for patients under therapy:

  • Stage of cancer
  • Levels of Prostate specific antigen (PSA)before therapy began
  • Gleason score.

Decreased levels of PSA to normal range after hormonal therapy depicts great prognosis. Similarly ,the prognosis is very bad for patients with a higher grade or stage of cancer .

ROUTES OF METASTASIS

Like all other cancers, prostate cancers also invade neighboring tissue or spread to other distant organs. This may be achieved by:

  • Local invasion:

Tumors which are locally situated, grow bigger and violently puncture into seminal vesicles, the bladder and other organs nearby. 

  • Hematogenous spread:

Cancer cells spread by blood vessels to other regions of the body, mostly bone. These sites of spread include pelvic bones, lower lumbar vertebrae, femoral head, rig cage and skull. 

  • Lymphatic spread:

Cancers spread through lymphatic vessels to lymph nodes along the rectum or obturator fossa.This spread continues to lymph nodes above the clavicle.

CRITERIA FOR STAGING

The staging is done using the following criteria: (TNM)

  • Tumor size (T)
  • Lymph node involvement (N)
  • Whether cancer spreads to other organs or not (M)

STAGES

The stage of prostate cancer is a very important factor for its treatment.It is also a great assessment tool for prognosis. Based on the criteria above we have the stages of prostate cancer .

Stage 1:

The cancerous cells are localized and non-invasive .They are normally found after examinations or screenings. This stage is mostly asymptomatic.

Stage 2:

Cells are still localized within the capsules of the prostate gland.

Stage 2A:

Mass localized in less than half of one lobe

Stage 2B:

Mass localized in one lobe .

Stage 2C:

Tumor confined to both lobes

Stage 3:

Tumor punctures capsule and invades nearby tissues .

Stage 3A:

Extension of tumor beyond capsule at a single or both sides into the neck of urethra

Stage 3B:

Extension of tumor behind capsule into both seminal vesicles

Stage 4:

Cancerous cells invade nearby organs like the rectum and pelvic wall. These cells may also spread to distant lymph nodes or bones .

DIAGNOSIS

To diagnose prostate cancer, a medical doctor performs several tests and examinations. These tests are  listed below.

 A.SCREENING TESTS

These tests are mostly done in men who are at risk of developing prostate cancer .Other men from age 55 and above do these tests to determine if they are developing prostate cancer or not .These tests are normally done when there is no manifestation of prostate cancer. Some screening tests include:

  • Digital Rectal Exam (DRE):

    A doctor wears gloves and inserts the finger through the anus into the rectum to feel and check for lumps around the prostate.Irregularities in shape and size of the gland can also be detected .

  • Test For Prostate Specific Antigen(PSA):

PSA is a protein produced in very low amounts in normal men without prostate cancer or any prostate related disease. High levels of PSA in blood may suggest prostate cancer, however this is not always the case. This is because other non-malignant conditions may increase PSA.

B.CONFIRMATORY TESTS.

These tests are done after a suspicion of a prostate neoplasia or tumor. They can also be done when prostate cancer is already detected. This is to affirm the presence of cancer in the prostate after screening procedures .

  • Transrectal Ultrasonography (TRUS):

This ultrasound is done after abnormalities are detected in a screening procedure. An image of the prostate is produced and abnormalities when present are seen using a machine that produces soundwaves to visualize internal structures.

  • Prostate Biopsy:

A doctor obtains tissue samples of the prostate gland and examines the cells under a microscope. This is done by comparing the structural deviations of the cancerous cells to the normal ones. This is the core concept on which the Gleason Scoring System is developed.

WHAT IS THE GLEASON SYSTEM OF GRADING PROSTATE CANCER?

Tissue samples of the prostate gland are observed under the microscope.The abnormal cells are compared to normal cells of the prostate gland. The determination of how the abnormal cells deviate from the normal is done using the Gleason system.

The scale uses the differentiation of cancer cells to grade prostate cancer. It determines how aggressive the cancer is.

To use this system, five main appearances of the tissue samples under the microscope are used:

  • Cancerous cells are just like normal prostate cells. Cells are uniform and small in size and are well differentiated.
  • Cancerous cells are larger than normal cells. The cells have increased stroma tissues and are moderately differentiated.
  • These cells have invasive appearances. They appear to invade nearby tissues under the microscope.They are moderately differentiated.
  • The sample tissues appear as irregular neoplastic glandular cells invading nearby tissues. The cells do not look like normal prostate cells. They are poorly differentiated.
  • The cells are spread out. They are undifferentiated cells with no glandular appearance .

To give the Gleason score two areas of the sample are observed:

  • The area where the cancerous cells stand out the most.
  • The next most outstanding area of cancerous cells.

Area one is graded 1-5 and the same happens with Area two .The sum of grades of these two areas give the final Gleason score .This score begins from 2, which indicates a non-aggressive carcinoma to 10, which is a more aggressive carcinoma.

A score above below 7 has a good treatment outcome. A score above 7 is associated with a poorer response to treatment and a poorer prognosis.

 C.Imaging tests

These tests are done to check if the cancer has travelled to other parts of the body or invaded nearby tissues.

  • Magnetic Resonance Imaging (MRI)
  • Computed Tomography (CT)
  • Bone Scan or Single -photon emission computed tomography (SPECT)
  • Ultrasound.

PREVENTION AND MANAGEMENT

  • Dietary management:

Eating fruits and vegetables will help reduce the risk of prostate cancer .

  • Regular Exercise:

Working out reduces cancer risk by reducing body weight.

  • Medications for high risk men to prevent prostate cancer:

These drugs are 5-Alpha Reductase inhibitors, and work by preventing the conversion of testosterone to dihydrotestosterone(DHT), by inhibiting the enzyme 5-Alpha reductase. The absence of DHT prevents prostate enlargement.

 

 TREATMENT

  • Patients with asymptomatic low grade cancers undergo regular checkups, examinations and monitoring without any active treatment therapies. This is called Active Surveillance
  • Radiation therapy:

High energy electromagnetic waves are used to kill cancerous cells.

  • Hormone therapy:

Drugs are given to prevent production of testosterone or to prevent testosterone from reaching cancerous cells. This starves cancerous cells, reducing their growth rate and resulting in their death. Some of these drugs include:

  • Testosterone production inhibitors: Histrelin, Leuprolide, Triptorelin
  • Androgen Receptor blockers: Flutamide,Nilutamide
  • Surgery:

  • Removal of the prostate gland (prostatectomy)
  • Removal of both testes to prevent the production of testosterone (bilateral orchidectomy).
  • Freezing of cancer cells to kill them(Cryosurgery)
  • Immunotherapy:

Boosting the body’s immune system to help it kill cancer cells. It is also called biological therapy.

  • Chemotherapy:

Use of Drugs to kill cancer cells .