The Application of Androgen Deprivation Therapy for Prostate Cancer

Introduction:

The prostate gland is a walnut-shaped gland of the urogenital system. It is the largest accessory gland of the male reproductive system. The cancerous growth of the epithelial cells of the prostate gland is known as prostate cancer. This is one of the most common cancers seen in men. It is the fifth leading cause of death in men in the world. Traditional treatment options like surgery, radiation therapy, and chemotherapy can be used for the treatment of such cases. Recently, a type of treatment known as androgen deprivation therapy has been used for curing prostate cancers.

What Is Prostate Cancer?

The prostate is situated at the base of the urinary bladder. It is situated just above the urethral sphincter muscle. The main function of the prostate gland is to secrete proteolytic enzymes. These enzymes help in breaking down the factors responsible for coagulation of semen. This maintains the fluidic state of the semen and helps in its movement. Prostate cancer usually arises from the peripheral zone and spreads quickly to the periphery due to its proximity to the neurovascular bundle. The commonest type of prostate cancer is adenocarcinoma of the prostate. Other types of prostate cancer are small cell carcinoma, neuroendocrine tumors, transitional cell carcinoma, and sarcoma.

Etiology of Prostate Cancer:

The etiological factors associated with prostate cancer are:

• Genetics is one of the most common causes of prostate cancer. Genetic mutation is related to genes like BRCA, RNASEL, HOXB13, and ATM genes.

• Increased age is another risk factor. This type of carcinoma is mainly seen in men who are older than 40 years. Familial history is another important etiological factor related to prostate cancer. The incidence of prostate cancer in fathers and brothers increases the risk factor of prostate cancer by sixfold.

• Infection conditions are also related to the increased incidence of prostate cancer. Infection caused by human papillomavirus (HPV) is linked to an increased risk of prostate cancer.

• A higher incidence of prostate cancer is seen in black people of African descent. The severity of disease and mortality is high in those individuals.

• Excessive smoking, alcoholism, and obesity are also considered etiological factors for prostate cancer.

Symptoms:

The symptoms of prostate cancer are:

• Increased frequency of urination.

• Urine flow is weak, and it's hard to maintain a steady urinary flow rate.

• Presence of blood in the urine.

• Pain in the lower back region.

• Pain and burning sensation during urination.

• The prostate gland becomes swollen up, hard, and irregular on palpation. The prostate gland is usually palpated through digital rectal examination.

• Unexplained weight loss, pain in the low back region, and tiredness can also be found.

• A high level of prostate-specific antigen is linked to the hyperactivity of the prostate cells and prostate cancer.

What Are the Treatment Options?

The treatment option for prostate cancer depends upon the extent of the spread of the cancer and the severity of the condition. The treatment options are:

1. Radical prostatectomy and pelvic lymphadenectomy (PLDN) are surgical procedures done for the treatment of prostate cancer. Radical prostatectomy is not done in aggressive cases due to the high rate of positive surgical margin, lymph node metastasis, and high rate of recurrence. Involved lymph nodes are removed by pelvic lymphadenectomy. Surgical technique alone can not be used as a treatment option for prostate cancer. Other treatment procedures should be combined with it.

2. Radiation therapy like External-beam radiotherapy (EBRT) and brachytherapy can be used as a second-line of treatment modality for curing prostate cancer. Also, advanced methods of radiotherapy like low-dose-rate brachytherapy (LDRB). In this procedure, radioactive seeds are inserted into the offending site through ultrasound guidance. This technique is used as an adjunct to surgical protocol. High-dose-rate brachytherapy (HDRB) is used as single monotherapy for prostate cancer treatment. Proton beam therapy (PBT) is another modern form of radiation therapy that uses ionizing radiation for localizing radiation.

3. In the cryosurgical procedure, extreme cold is applied to remove diseased tissue. Liquid nitrogen is used for treating the cases of low-risk localized cases of prostate cancer.

What Is Androgen Deprivation Therapy?

Androgen deprivation therapy is also known as hormone replacement therapy. Androgens are male sexual hormones that help in male reproduction and sexual activity. These hormones act through androgen receptors. These receptors are needed for the normal development and functioning of the prostate gland. These androgen receptors bind to testosterone and dihydrotestosterone (DHT), which leads to the supply of y secretory proteins to the prostate gland, such as prostate-specific antigen (PSA). Also, the transcriptional activity of the androgen receptors is maintained by these hormones. Activation of androgen receptors leads to the growth and proliferation of prostate epithelial cells. Androgens play a pivotal role in the activation of androgen receptors.

Androgen deprivation therapy is considered the first line of treatment for symptomatic metastatic prostate cancer. Also, this can be used as an adjunct with high-grade, clinically localized prostate cancer who undergo radiotherapy to improve survival rate. Different types of drugs belong to this category are:

1. Gonadotropin-Releasing Hormone (GnRH) Agonists: Drugs belonging to this category act on the anterior pituitary gland. This causes a decrease in the release of l luteinizing hormone and down-regulates the functioning of GnRH Receptors. Leuprolide and Goserelin are the drugs that belong to this category.

2. GnRH Antagonists: Abarelix is a drug that belongs to this category that acts on the anterior pituitary gland. This drug inhibits the functioning of GnRH Receptors.

3. Androgen Receptor Antagonists: These drugs act on the prostate gland. They inhibit the androgen receptor’s ligand domain activity through competitive binding. Drugs belonging to this category are Flutamide, Bicalutamide, and Nilutamide.

4. 5 alpha-Reductase Inhibitors: These drugs prevent the conversion of testosterone to dihydrotestosterone (DHT) by inhibiting the activity of 5 alpha-Reductase. Finasteride, a drug that belongs to this group, acts on the prostate gland.

5. Adrenal Ablating Drugs: Ketoconazole, a drug that belongs to this category, decreases androgen synthesis by inhibiting Cytochrome P450 Enzymes.

What Are the Adverse Effects?

The adverse effects related to androgen deprivation therapy are:

1. One of the main adverse effects of hormone replacement therapy is vasomotor symptoms like hot flashing.

2. Reduced bone marrow densities, joint pain, and micro-fractures can be seen.

3. Male endocrine dysfunction can be observed. As a result, symptoms like high sugar levels, high triglyceride levels, and insulin-resistant diabetes can be seen in patients.

4. Gynecomastia, or the development of male boobs, can be observed.

5. Cardiovascular symptoms like hypertension can be seen.

Conclusion:

Prostate cancer is one of the most preventable cancers in males. It is also one of the major causes of male mortality. Androgen deprivation therapy or hormonal replacement therapy can be used in the treatment of symptomatic metastatic prostate cancer. Complications like endocrine dysfunctions, hot flashes, and gynecomastia are seen in such cases of treatment.