Everything you need to know about Prostate Cancer

by Gurpreet Kaur Bumrah, Shoolini University, Himachal Pradesh

Understanding Prostate Cancer

The prostate is a small organ located below the urinary bladder and in front of the rectum in men. It is typical for the size of the prostate to increase with age. In younger men, it is about the size of a walnut. The prostate delivers a smooth liquid, which is part of the semen that feeds the sperm.
Prostate cancer is defined as the uncontrolled growth of cells in the prostate gland. Almost all prostate cancers diagnosed after biopsy are diagnosed as adenocarcinoma of the prostate while the rarer types would be a small cell carcinoma, neuroendocrine tumour, transitional cell carcinoma, or a sarcoma. Many cases of prostate cancer develop slowly over time and do not spread outside the prostate gland. More aggressive cases that spread outside the prostate gland, on the other hand, can be life-threatening. Early detection and treatment of prostate cancer can reduce the risk of mortality, especially when the cancer is treated while it remains confined to the prostate gland. Today, prostate cancer has become one of the most common types of cancer.

Reasons behind the onset of Prostate Cancer

The precise cause of prostate cancer is largely unknown. Cancer develops when cells in the prostate incorporate a drastic change in their DNA (mutation), causing them to grow and multiply more quickly than normal cells. These abnormal cells can eventually combine to form a tumour, wreaking havoc on surrounding tissues and organs. These abnormal cells can separate from the tumour and spread (metastasize) to other organs and tissues in aggressive cases of prostate cancer. When the prostatic tissue rapidly replicates, adenocarcinoma develops.

This results in benign prostatic hypertrophy and, in the worst-case scenario, prostate cancer. This occurs after the age of 60-65. Benign prostatic hypertrophy is frequently associated with frequent urination and incontinence. The DNA of a cell contains the guidelines that instruct the cell. The modifications instruct the cells to grow and divide at a faster rate than normal cells. When other cells would die, the abnormal cells would continue to live.

Risk Factors

Factors that can increase the risk of prostate cancer are:

1. Age progression: The risk of prostate cancer increases with one’s progression in age. It’s most common after age 50. This can be due to many reasons, primarily due to rise in abnormal cells that are approaching senescence and due telomere shortening.
2. Race: For undetermined reasons, people of the African-American origin were reported to have a higher risk of developing prostate cancer as compared to people of other races, which is mostly aggressive or advanced.
3. Family History: With a case of strong family history of breast cancer (BRCA1 & BRCA2) and prostate cancer, the danger of acquiring the disease increases.
4. Obesity: People who are obese have a higher risk of developing prostate cancer compared to people that are overweight or are healthy, although this is not absolute since studies have depicted mixed results. In obese people, the cancer is bound to be more forceful and firm to return (relapse) after starting treatment.
5. Cigarette Smoking: Cigarette smoke affects the circulation of hormones and various carcinogens from it can give rise to prostate cancer (risk level: low to moderate), although the exact mechanisms of the same are still being studied.
6. Alcoholism: Consumption of alcoholic beverages can induce the proliferation of tumour cells. It has been reported that treatment with white wine lead to mild cell proliferation of the PC3 cell-line.
7. Hormonal causes: Abnormalities in the circulation and regulation of endocrine hormones are linked to onset of this cancer as well.

Symptoms

Prostate cancer may cause no signs or symptoms in its early stages. More advanced prostate cancer may cause signs and symptoms such as:

1. Trouble/Painful urinating including a slow or weak urinary stream or the need to urinate more often, especially at night (nocturia). Painful urination is also known as dysuria which tends to be more common in older men than in younger men. Dysuria is characterized by feelings of discomfort, pain, and/or burning when urinating which can also be a sign of other medical conditions, including a urinary tract infection or sexually transmitted infection.
2. Blood in the urine and semen- Blood in the urine that you can see is known as gross haematuria. Gross haematuria usually isn’t painful but can be alarming when in the urine stream. Other potential causes of gross haematuria include urinary tract infection, kidney infection, and kidney stones.
   Blood in the semen may indicate prostate cancer as the prostate gland produces part of the fluid in the semen. The presence of a tumour in the prostate gland can rupture blood vessel walls to cause blood to appear in semen.
3. Losing weight without trying to.
4. Erectile dysfunction- Erectile dysfunction is the inability to achieve or maintain an erection, which is caused by a wide range of medical conditions. It may be an early sign of prostate cancer if other early symptoms are also detected.
5. Pain in the hips, back, chest, or other areas from cancer that have spread to bones leading to pain.
6. Weakness or numbness in the legs or feet, loss of bladder or bowel control from cancer pressing on the spinal cord.

Types of Prostate Cancer

More than 95% of prostate cancers are adenocarcinomas. Several other forms of prostate cancer are extremely rare. The different types of prostate cancer start in distinct cells. Doctors analyse the prostate tissue in a lab to see what kinds of cells have cancer in them and use this information along with the stage and the grade to help decide the treatment plan.

1. The Most Common Prostate Cancer: Adenocarcinoma
   Adenocarcinomas occur almost anywhere in the body. They are formed in the glandular epithelial cells that line the inside of the organs and secrete mucus, digestive juices, or other fluids. In the prostate, adenocarcinoma is also called glandular prostate cancer. Symptoms include a frequent urge to urinate, painful urination and ejaculation, and blood in the semen.
   a. Acinar adenocarcinoma is- The most common type of prostate cancer. In this case, carcinoma occurs in the gland cells that are present in the lining of the prostate gland.
   b. Ductal adenocarcinoma– This type starts in the cells that line the ducts (or tubes) of the prostate gland. It’s usually more aggressive than the other type.
   Other Rare Forms of Prostate Cancer:
   
2. Around 5% of prostate cancers are not adenocarcinoma. They may be the following:
   a. Small-cell carcinoma– This type makes up about 1% of prostate cancers. It develops in small round cells in the prostate and can rapidly spread to other parts of the body, such as the bones.
   b. Squamous cell carcinoma– Fewer than 1% of men with prostate cancer have this type. It is developed in flat cells that encapsulate the prostate. This type is also a faster, more aggressive form.
   Transitional cell (or urothelial) cancer- This cancer grows in the urethra, the tube that carries urine outside the body. Often, it starts in the bladder before spreading.
   3. Neuroendocrine tumours– These tumours can emerge from neuroendocrine cells anywhere in the body. These cells make hormones to help the function of the organ they occupy, such as the lungs, stomach, and pancreas. Rarely do tumours grow inside neuroendocrine cells of the prostate.
   Soft tissue sarcoma- This starts in supportive tissues which include muscle, nerves, fat, and blood vessels. In the prostate, this cancer is extremely rare, accounting for less than 0.1% of cases, that’s fewer than 1 in 1,000 men with prostate cancer.

Diagnosis

Prostate cancer can be treated in several different ways depending on the seriousness of the cancer and the rate at which it is growing.
All treatment options are determined by the severity of the condition and the patient’s current health status. Radiation plays a huge part in the treatment of prostate cancer. This comes in many forms—external beam radiation, prostate seed implants, proton therapy, high-intensity focused ultrasound, and chemotherapy. For advanced diseases, radioactive isotopes can be administered to make the patient more comfortable. Low-grade prostate cancer may not require treatment, especially if there aren’t any hampering symptoms. In these instances, active surveillance of symptoms and undergoing regular blood testing, rectal exams, and prostate biopsies are prescribed.

Screening methods include:
Digital rectal examination (DRE) helps to find prostate problems- DRE is a standard way to check the prostate. With a gloved and lubricated finger, the doctor feels the prostate from the rectum. The test lasts about 10-15 seconds. This exam checks for:
1. The size, firmness, and texture of the prostate
2. Hard areas, lumps, or growth spreading beyond the organ
3. Pain caused by touching or pressing the organ.
4. Prostate-specific antigen (PSA): PSA is a protein made by prostate cells. It is normally secreted into ducts of the prostate, where it assists in making semen, but sometimes it leaks into the blood. PSA levels in the blood can be determined via a blood test known as the PSA test. PSA levels in the blood can occasionally suggest prostate cancer.
5. Definite diagnosis based on the biopsy of the prostate tissue- If symptoms or test results suggest prostate cancer, the doctor will ask a specialist (a urologist) for a prostate biopsy. For a biopsy, a small amount of tissue samples are taken from the prostate. This helps lower the chance of missing any areas of the gland that may have cancer cells. Magnetic resonance imaging investigations and imaging tests may be done to determine the spread’s distance (metastasis).

Treatment

Bilateral orchiectomy : This is the surgical removal of both testicles eliminating the main source of testosterone production.

LHRH agonist : LHRH agonists block the testicles from getting information from the body in order to produce testosterone.

LHRH antagonist: Also called a gonadotropin-releasing hormone (GnRH) antagonist, stops the testicles from producing testosterone like LHRH agonists, reduce testosterone levels more quickly and prevents association with LHRH agonists.

Androgen receptor (AR) inhibitors: This blocks testosterone from binding to androgen receptors, which are chemical structures in cancer cells that allow testosterone and other male hormones to enter the cells.

Apalutamide: This FDA approved drug is for the treatment of non-metastatic castration-resistant prostate cancer and for metastatic castration-sensitive prostate cancer in combination with hormonal therapy.

Androgen synthesis inhibitors: Glands like adrenal glands can also produce testosterone that can drive cancer cells growth. Androgen synthesis inhibitors work by inhibiting an enzyme called CYP17, which prevents cells from producing testosterone.

Combined androgen blockade: Androgen receptor inhibitors are combined with bilateral orchiectomy or LHRH agonist treatment to maximize the blockade of male hormones or to prevent the flare associated with treatment with LHRH agonists. Side effects of Hormonal therapy inclides impotence, breast tissue growth, hot flashes and weight gain.

Freezing Or Heating Prostate tissue can be frozen using cryoablation or cryotherapy, which makes use of cold gas to freeze and destroy the cancerous prostate tissues. High-intensity focused ultrasound energy can also be utilised to heat and kill prostate tissue.

Surgery: Surgery to remove the prostate gland may be undertaken, especially if the cancer is limited to the prostate gland.

Radical (open) prostatectomy: A surgical removal of the entire prostate and the seminal vesicles along with lymph nodes in the pelvic area which may also be removed.Robotic or laparoscopic prostatectomy: This surgery is less invasive and shortens the recovery time. A camera and tools are placed into the patient’s belly through tiny keyhole incisions. The robotic devices are then directed by the surgeon to remove the prostate gland.

Therapy approaches:

Bilateral orchiectomy : This is the surgical removal of both testicles.

Transurethral resection of the prostate (TURP): TURP is used to relieve symptoms of a urinary blockage.

Radiation Therapy: Radiation therapy destroys cancer cells in the prostate using high-powered energy conducted by a specialist, Radiation oncologist. Types of treatments involved in radiation therapy are as follows:

External-beam radiation therapy: External-beam radiation therapy is the most common type of radiation treatment in which a machine located outside the body to focus a beam of X-rays on the area with the cancer.

One method of external-beam radiation therapy is called hypo fractionated radiation therapy. The patient receives a higher daily dose of radiation therapy over a shorter period, instead of lower doses over a longer period of time. Extreme hypo fraction radiation therapy is when the entire regime is delivered in 5 or fewer treatments. Stereotactic body radiation treatment (SBRT) or Stereotactic Ablative Radiation therapy (SAR) is another term for this method.

Brachytherapy– Also called as internal radiation therapy, is the insertion of radioactive sources directly into the prostate. The sources, called seeds, give off radiation just around the area where inserted and is left either for a short time (high-dose rate) which is usually left in the body for less than 30 minutes, but it may need to be given more than once., or for a longer time (low-dose rate) which is left in the prostate permanently and its functions upto about an year since insertion. However, their working depends on the source of radiation.

Intensity-modulated radiation therapy (IMRT)– IMRT is a type of external-beam radiation therapy in which CT scans is used to form a 3D image of the prostate before treatment. A computer utilises this information about the prostate cancer’s size, shape, and location to calculate how much radiation is required to eradicate it. Using IMRT, high doses of radiation can be directed at the prostate without increasing the risk of damaging nearby organs.

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, these protons can destroy cancer cells. Proton treatment does not appear to be any more beneficial to men with prostate cancer than standard radiation therapy, according to current data.

Radiation therapy: may cause side effects during treatment, like increased urinary urge or frequency, problems with libido, problems with bowel function, including diarrhoea, rectal discomfort or rectal bleeding and fatigue.

Chemotherapy: Chemotherapy can destroy rapidly growing cells using combination of drugs. Chemotherapy is often used for aggressive and advanced castration-resistant prostate cancer and newly diagnosed or castration-sensitive metastatic prostate cancer cells that have metastasize to other body sites. Usually, chemotherapy is administered through intravenous line in a series of treatments for several months. Unfortunately, chemotherapy often kills other fast-growing body cells like hair cells, mucosal cells, and cells that line the gastrointestinal tract which results in several unwanted side effects. A chemotherapy regimen consists of a specific number of cycles given over a set period of time.

There are several standard drugs used for prostate cancer, beginning with docetaxel (Taxotere) combined with prednisone. Recent research shows adding docetaxel to hormonal therapy for newly diagnosed or castration-sensitive metastatic prostate cancer patients, has significantly improved longevity and stops the disease from growing and spreading. Cabazitaxel (Jevtana) is another approved drug for metastatic castration-resistant prostate cancer, is a microtubule inhibitor.

The side effects of chemotherapy depend on the individual, the type of chemotherapy received, dosage, and the length of treatment, usually includes fatigue, sores in the mouth and throat, diarrhoea, nausea and vomiting, constipation, blood disorders, nervous system effects, changes in thinking and memory, sexual and reproductive issues, appetite loss, pain, and hair loss. The side effects of chemotherapy usually go away after treatment has finished. However, some side effects may continue, come back, or develop later.

Immunotherapy: Immunotherapy helps the body identify and attack cancer cells. This involves taking a sample of immune cells from the patient and using genetic engineering to change them into cancer-fighting cells that destroy prostate cancer. Other forms of immunotherapy involve using drugs that trains the immune system to destroy cancer. Immune therapy for prostate cancer has been using vaccine, but it does not prevent prostatic cancer from developing in men. The prostate cancer “vaccine” is an individualized treatment method, designed to provide immune cells derived from a single patient’s own cells. These cells are laboratory enhanced immune cells that become capable of killing or damaging the patient’s own prostate cancer cells. Like hormone therapy, these vaccines do not kill off all cancer cells and is currently used to slow the progression of aggressive cancers, especially those unresponsive to other treatments.

Remission and the chance of recurrence

Remission can be temporary or permanent. There are treatments to help prevent recurrence, such as hormonal therapy and radiation therapy, it is important to talk with the doctor about the possibility of the cancer returning. Nomograms are methods that your doctor can use to determine someone’s likelihood of recurrence. Remission can also be handled with palliative care.

Prevention Strategies

Fighting and preventing prostate cancer requires one to follow the following short guidelines:
1. Choose a healthy diet full of fruits and vegetables.
2. Choose healthy foods over supplements
3. Exercise most days of the week.
4. Maintain a healthy weight.
5. Take a genetic test
6. Talk to the doctor about increased risk of prostate cancer

Also read: BioXone Biosciences Workshop Cum Internship

Sources:

1. Pienta, K. J., & Esper, P. S. (1993). Risk factors for prostate cancer. Annals of internal medicine, 118(10), 793-803.
2. Ilic, D., Neuberger, M. M., Djulbegovic, M., & Dahm, P. (2013). Screening for prostate cancer. Cochrane Database of Systematic Reviews, (1).
3. Rawla, P. (2019). Epidemiology of prostate cancer. World journal of oncology, 10(2), 63.
4. Joshu, C. E., Mondul, A. M., Meinhold, C. L., Humphreys, E. B., Han, M., Walsh, P. C., & Platz, E. A. (2011). Cigarette smoking and prostate cancer recurrence after prostatectomy. JNCI Journal of the National Cancer Institute, 103(10), 835–838
5. Vartolomei, M. D., Kimura, S., Ferro, M., Foerster, B., Abufaraj, M., Briganti, A., Karakiewicz, P. I., & Shariat, S. F. (2018). The impact of moderate wine consumption on the risk of developing prostate cancer. Clinical Epidemiology, 10, 431–444

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