Prostate Cancer

Prostate cancer is a kind of cancer that occurs in the prostate, a small nut-shaped gland that is found only in men and produces the seminal fluid that nourishes and transports sperm. Prostate cancer begins when prostate cells begin to grow out of control.

The prostate is under the bladder (the hollow organ for the storage of urine) and in front of the rectum (the last part of the intestine). Just behind the prostate seminal vesicles. These glands produce the greatest amount of fluid for sperm. The urethra, which is the tube that carries urine and sperm out of the body through the penis, passes through the center of the prostate.

The size of the prostate may change with age. In younger men, it is about the size of a nut, but it can be much larger in older men.

Prostate cancer is one of the most common types of cancer in men. In fact, in 2019, the American Cancer Society (ACS) predicts about 174,650 new diagnoses of prostate cancer and about 31,620 deaths from this type of cancer.

About one in nine men will be diagnosed with prostate cancer at some time in their life. However, only 1 in 41 of them will die as a result of this disease.

In general, prostate cancer develops slowly and is initially limited to the prostate, where it cannot cause serious damage. However, while some types of prostate cancer develop slowly and may require minimal or no treatment, other types are aggressive and can spread rapidly.

Prostate cancer detected early, when still confined to the prostate, has a better chance of successful treatment.

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Types of Prostate Cancer

Almost all prostate cancers are adenocarcinomas. These cancers develop from gland cells (the cells that cause prostate fluid to add to sperm).

Other types of cancer that can develop in the prostate are rare and they include:

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

Symptoms of Prostate Cancer

It may not cause any signs or symptoms in its early stages but at a later stage can cause signs and symptoms such as:

• Difficulty urinating
• Decreased force in the flow of urine
• Blood in the sperm or urine
• Discomfort in the pelvic area
• Bone-ache
• Erectile dysfunction
• In some cases, painful ejaculation
• Difficulty achieving or maintaining an erection
• Pain or discomfort when sitting if there is an enlargement of the prostate

Advanced Symptoms

• Bone fracture or bone pain, especially in the hips, thighs, and shoulders
• Increased difficulty in breathing during previously well-tolerated activities
• Edema or swelling of the legs or feet
• Weightloss
• Tiredness
• Changes in bowel habits
• Back pain

When to see a doctor

Make an appointment with your doctor if you have any signs or symptoms that concern you.

The debate about the risks and benefits of prostate cancer screening continues and medical organizations differ in their recommendations. Discuss the detection of prostate cancer with your doctor. Together, they can decide what is best for you.

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Causes of Prostate Cancer

We do not know what causes prostate cancer.

However, doctors know that prostate cancer begins when some prostate cells become abnormal. Mutations in the DNA of abnormal cells result in faster cell growth and division than normal cells. Abnormal cells continue to live, while other cells die. The accumulated abnormal cells form a tumor that can develop to invade neighboring tissues. Some abnormal cells can also break off and spread (metastasize) to various other body parts.

Possible Precancerous Conditions of the Prostate.

Some research suggests that prostate cancer comes from a precancerous condition, but it is not yet a certainty. These conditions are sometimes encountered when a man undergoes a prostate biopsy (harvesting small parts of the prostate to detect cancer).

Prostatic Intraepithelial Neoplasia (PIN)

In PIN, the appearance of the prostate cells changes when viewed with the microscope, but the abnormal cells do not appear to develop to other parts of the prostate (as would be the cancer cells). According to the abnormal appearance of cellular models, they are classified as follows:

• Low grade PIN: Prostate cell patterns seem almost normal.
• High grade PIN: Cell patterns seem more abnormal.

The low grade PIN does not seem to lead to a risk of prostate cancer. On the other hand, there is this belief that a high grade PIN is a possible precursor to prostate cancer. The discovery of high grade prostate cancer after you undergo a biopsy means you are more likely to develop prostate cancer over time.

PIN begins to appear in the prostate of some men as early as 20 years. But many men with PIN will never develop prostate cancer.

Proliferative Inflammatory Atrophy (PIA)

In PIA, prostate cells appear smaller than normal and there are signs of inflammation in the area. PIAs are not cancerous, but researchers believe that PIAs can sometimes lead to a high grade PIN or directly to prostate cancer.

Risk factors

Factors that may increase the risk of include:

1. Age: Your risk increases with age. Specifically, the risk increases after 50 years, but it is rare before 45 years.
2. Family history: Those who have a history of prostate cancer in their family, are more likely to develop it. In addition, if you have a history of breast cancer risk (BRCA1 or BRCA2) in your family, your risk of having it may be higher.
3. Race: For reasons not yet determined, black men have a higher risk of prostate cancer than men of other races. In black men, it is also more likely to be aggressive or advanced. Asian and Hispanic men have a lower risk than black or white men.
4. Obesity:  Obese men who have been diagnosed with it may be more likely to have advanced disease, which is more difficult to treat.

Other possible factors

Some evidence suggests that other factors may play a role, but there is a need for more studies to confirm this. Some of these other possible factors include:

• Diet
• Obesity
• Smoking
• Exposure to chemicals, such as Agent Orange Herbicide
• Inflammation of the prostate
• Sexually transmitted infections
• Vasectomy

Complications

The complications of prostate cancer and its treatments include:

1. Cancer that spreads (metastasis): Prostate cancer can spread to close organs, such as the bladder or travel through the bloodstream or lymphatic system to the bones or other organs. When it spreads to the bones, it can cause pain and fractures. Although it can still be controlled when it has spread to other parts of the body, it is unlikely to be cured.
2. Incontinence: Prostate cancer and its treatment can cause urinary incontinence. The treatment of incontinence will depend on the type affecting you, its severity and the likelihood that it will improve over time. Treatment options may include medications, catheters, and surgery.
3. Erectile dysfunction: Erectile dysfunction may be the result of prostate cancer or its treatment, which includes surgery, radiation or hormone therapy. Medications, erection and surgical vacuum devices are available to treat erectile dysfunction.

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Prevention of Prostate Cancer

1. Choose a healthy diet rich in fruits and vegetables. Avoid high-fat foods and focus on a variety of fruits, vegetables, and whole grains. Fruits and vegetables contain many vitamins and nutrients that can contribute to your health. There is not enough proof to conclude that dieting can help prevent prostate cancer. However, a healthy diet that includes a variety of fruits and vegetables can improve your overall health.
2. Choose healthy foods rather than supplements. No studies have shown that supplements play a role in reducing the risk of prostate cancer. Instead, choose foods rich in vitamins and minerals so you can maintain healthy levels of vitamins in your body.
3. 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 do not exercise have higher PSA levels, while men who exercise may have a lower risk. Try to exercise most days of the week.
4. Maintain a healthy weight. If your current weight is healthy, make sure to continue exercising to maintain it. If you need to lose weight, add more exercise and avoid taking more calories. Ask your doctor to help you create a healthy weight loss plan.
5. Talk to your doctor about the risk of prostate cancer. Men at high risk may consider taking medications or other treatments to reduce their risk. Some studies suggest that taking 5-reductase inhibitors, including finasteride (Propecia, Proscar) and dutasteride (Avodart), may reduce the overall risk. These drugs can control prostate enlargement and hair loss in men.

However, there is some evidence that these drugs may be associated with an increased risk of prostate cancer (high-grade). If you are concerned about your risk of having it, talk to your doctor.

Diagnosis

If anybody has symptoms of this ailment, the doctor will likely ask these questions

• ask about symptoms
• perform a urine test to look for other biomarkers
• ask questions about personal and medical history
• perform a blood test to assess PSA levels
• perform a physical exam, which may include a digital rectal exam (DRE)

During a DRE, the doctor will manually check for any abnormalities of the prostate with your finger.

Additional Tests

If a doctor suspects cancer, he may recommend additional tests, such as:

A PCA3 test: This test looks for a PCA3 gene in the urine.

Transrectal ultrasound: this involves inserting a probe that has a camera into the rectum.

A biopsy: a doctor will take a tissue sample to examine with a microscope.

Only a biopsy can confirm the presence and type of cancer.

A person who requires monitoring or treatment may require an MRI or routine CT scan.

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The Stages

The term staging cancer means describing the obvious extent of cancer in the body at the time of the initial diagnosis. The clinical evaluation of prostate cancer is based on the results of the pathology, physical examination, PSA and, if necessary, radiological studies. The cancer stage helps doctors understand the extent of cancer and plan its treatment. The results of the treatment from a similar Gleason score prostate cancer found at the same stage can help the doctor and the patient to make important decisions about which treatment options to recommend.

Cancer staging is described using what is known as the TNM system. “T” refers to a description of the size or extent of the original or primitive tumor. “N” describes the presence or absence of cancer and the degree of spread of the cancer to the lymph nodes that may be near or further from the original tumor. “M” describes the presence or absence of metastases, usually distant areas of the body other than regional (nearby) lymph nodes to which the cancer has spread. Cancers with specific TNM characteristics are grouped into stages, then Roman numbers are assigned to the stages. The numbers are used in increasing order as the extent of the cancer increases. The prognosis is eventually reflected taking into account the patient’s PSA score during the presentation, as well as his Gleason score when assigning a final stage designation.

The American Joint Commission on Cancer (AJCC) system for staging prostate cancer is as follows:

The T designations refer to the characteristics of the primary tumor of prostate cancer.

T1 prostate cancers cannot be seen on imaging tests or felt on the exam. They can be found accidentally during prostate surgery due to a supposedly benign problem, or during needle biopsy for a high PSA.

• T1a means that cancer cells make up less than 5% of the tissue removed.
• T1b means that cancer cells make up more than 5% of the tissue removed.
• T1c means that the tissue containing the cancer was obtained by needle biopsy for a high PSA.

T2 prostate cancers are those that can be felt during a physical examination of the prostate (digital rectal exam) or that can be visualized by imaging studies such as ultrasound, X-rays or related studies. The prostate is composed of two halves or lobes. The extent of the involvement of these lobes is described here.

• T2a means that cancer affects at least half a lobe of the prostate.
• T2b means that the cancer involves more than half of one lobe but does not affect the other lobe of the prostate.
• T2c means that the cancer has reached or touches both lobes of the prostate.

T3 prostate cancers have developed to the extent that the tumor extends outside the prostate. Adjacent tissues, including the capsule around the prostate, seminal vesicles, and bladder neck, may be involved in T3 tumors.

• T3a means that the cancer has spread beyond the capsule (the outer edge) of the prostate but not into the seminal vesicles.
• T3b means that the cancer has invaded the seminal vesicles.

T4 prostate cancers have spread outside the prostate and have invaded adjacent tissues or organs. This can be determined by examination, biopsy or imaging studies. T4 prostate cancer can affect the pelvic floor muscles, the urethral sphincter, the bladder itself, the rectum, the elevating muscles or the pelvic wall. T4 tumors have invaded adjacent structures other than seminal vesicles.

Traditionally, advanced prostate cancer was defined as a disease that had metastasized far beyond the prostate, surrounding tissues, and pelvic lymph nodes and was incurable. However, a more contemporary definition includes patients with a minor disease with a higher risk of progression and/or death from prostate cancer, in addition to those with widely metastatic disease.

The NCCN Guidelines for Prostate Cancer Version 2.2017 states the following:

Computed Tomography (CT)is used for initial staging in some patients, which includes:

• T3 or T4 disease, and
• T1 or T2 disease and nomogram probability of lymph node involvement greater than 10% may be candidates for pelvic CT. A nomogram is a predictive tool that takes a set of information (data) and can predict the results.

Standard Magnetic Resonance Imaging (MRI)techniques can be considered for the initial evaluation of high-risk patients, including

• T3 or T4 disease, and
• A T1 or T2 disease and a nomogram indicating a probability of lymph node involvement greater than 10% may be candidates for pelvic magnetic resonance imaging.

Bone scan is recommended in the initial evaluation of patients at high risk of skeletal metastases, which include:

• T1 disease with PSA greater than 20, T2 disease and PSA greater than 10, Gleason score greater than 8 or T3 / T4 disease, and
• Any stage disease with symptoms of bone metastases (eg, bone pain).

Nitrogen designations refer to the presence or absence of prostate cancer in adjacent lymph nodes, including the hypogastric, obturators, internal and external iliac nodes, and sacral nodes.

• N0 means that there is no obvious prostate cancer in the neighboring nodes.
• N1 means that there are signs of prostate cancer in the neighboring nodes.
• NX means that the lymph nodes cannot or have not been evaluated.

M refers to the presence or absence of prostate cancer cells in distant lymph nodes or other organs. Prostate cancer that has spread to the blood is most often transmitted first to the bones, then to the lungs and liver.

• M0 means that there is no evidence of the spread of prostate cancer to distant tissues or organs.
• M1a means that there is a spread of prostate cancer in distant lymph nodes.
• M1b means that there is evidence that prostate cancer has spread to the bones.
• M1c means that prostate cancer has spread to other distant organs, in addition to or instead of the bones.

Stratify prostate cancer by risk

NCCN guidelines stratify prostate cancer by risk. The risk groups are based on prostate cancer staging, Gleason score, PSA and the amount and extent of cancer-positive biopsy cores. Risk stratification can help decide which treatment option is best for each individual.

Very low risk: T1c stage, Gleason score ≤ 6, Gleason grade group 1, PSA <10 ng / ml, <3 prostate biopsy cores positive for cancer <50% in all cores, PSA density <0.15 ng / ml / g

Low risk: stage T1-T2a, Gleason score ≤ 6, Gleason grade group 1, PSA <10 ng / mL

Intermediate risk: stage T2b-T2c, Gleason score 3 + 4 = 7, Gleason grade group 2 or Gleason score 4 + 3 = 7, Gleason grade group 3 or PSA 10-20 ng / mL

High risk: T3a or Gleason grade 8, Gleason grade group 4 or Gleason 9-10, Gleason grade group 5, PSA> 20 ng / mL

Very high risk: stage T3b-T4, primary Gleason pattern 5, Gleason grade group 5 or> 4 cores with Gleason 8-10, Gleason grade group 4-5.

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Treatment

The treatment options for prostate cancer are many. Although it is an advantage because prostate cancer is so common in men, it can also cause great confusion. The following general description provides information about these options but is not a complete explanation.

NCCN treatment recommendations based on risk stratification are:

Very low risk

• Life expectancy <10 years – observation
• The Life expectancy 10-20 years – active surveillance
• Life expectancy> 20 years: active surveillance, external radiotherapy, brachytherapy or RRPX

Low risk

• Life expectancy <10 years – observation
• Life expectancy> 10 years: active surveillance, external radiotherapy, brachytherapy or RRPX

Intermediate risk

• Life expectancy <10 years – observation; BERT +/- ADT (4-6 months), +/- brachytherapy; brachytherapy
• Life expectancy> 10 years – RRPX +/- lymph node dissection EBRT +/- ADT (4-6 months) +/- brachytherapy; brachytherapy

High risk

• EBRT + ADT (2-3 years); EBRT + brachytherapy +/- ADT; RRPX in selected individuals

Very high risk

• EBRT + ADT in the long term; EBRT + brachytherapy +/- ADT in the long term; RRPX + lymph node dissection ADT or observation in some patients

The options for conventional medical treatment for prostate cancer are as follows:

• Observation
• Active surveillance\Surgery (radical prostatectomy: open, laparoscopic, robotic, perineal)
• Radiotherapy (external radiotherapy and brachytherapy)
• Focal therapy, including cryotherapy.
• Hormonal treatment
• Chemotherapy
• Immunotherapy/vaccine and other targeted therapies.
• Bone-directed therapy (bisphosphonates and denosumab)
• Radiopharmaceuticals (radioactive substances used as medicines).
• Research techniques, including high intensity, focused ultrasound (HIFU) and others.

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

Prostate Cancer at an Early Stage

A prostatectomy is a possible treatment for early stage prostate cancer.

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

Observation and Active Surveillance

These two options are not the same. Observation and active surveillance therapies share in common the initial decision to continue cancer treatment and periodically monitor cancer to determine if there is progression. The observation consists of monitoring the evolution of prostate cancer with the objective of treating cancer with palliative care for the appearance of symptoms or changes in the physical examination or PSA, which suggests that symptoms will develop soon. Observation therapy is not about curing cancer, but about treating the symptoms of cancer progression. Therefore, observation therapy is preferred in men with low-risk prostate cancer whose life expectancy is less than 10 years.

Active surveillance involves actively monitoring the progress of prostate cancer with the intention of intervening, with the intention of curing if the cancer seems to progress. Active surveillance is preferable in men with very low risk prostate cancer and a life expectancy of fewer than 20 years. Cancer progression may have occurred if a repeated biopsy shows a high Gleason score (Gleason 4 or 5) or if the cancer is detected in more biopsies or in a larger nucleus compared to the previous biopsy.

The NCCN Guidelines for prostate cancer (version 2.2017) take into account the following for active surveillance of prostate cancer:

1. The PSA test should not be obtained more than once every 6 months unless clinical changes warrant more frequent tests.
2. A DRE should not be performed more than once every 12 months unless clinical changes warrant a more frequent examination.
3. A prostate biopsy should be repeated within 6 months if the initial biopsy took away less than 10 cores or if the test results do not match the biopsy results.
4. Biopsy should be repeated every year to assess the progression of cancer.
5.  If life expectancy is less than 10 years, it is not necessary to repeat the biopsy.
6. If the PSA is up and the biopsy is negative, consider multiparameter magnetic resonance imaging.

Active surveillance has advantages and disadvantages. For benefits, it avoids unnecessary treatments and the possible side effects of such treatments. The disadvantages of active surveillance include the risk of lost healing, although this risk is very low if you are followed up regularly, as well as the need for periodic prostate biopsies and the side effects of prostate biopsy.

Observation has advantages and disadvantages. For the advantage, the observation avoids/delays the possible side effects of the treatment. However, there is a risk of problems with urination (urinary retention) or bone fractures before the start of treatment.

As reported in European Urology, Dr. Lu-Yao and his colleagues conducted a population-based cohort study of 31,137 Medicare patients 65 years of age and older diagnosed with prostate cancer in 1992-2009 and having initially benefited of a conservative treatment (without surgery, radiotherapy, cryotherapy or androgen deprivation treatment) followed until death on December 31, 2009 (for prostate cancer mortality) and on December 31, 2011 for general mortality and found that the results at 15 years with conservative management of prostate cancer T1c Gleason 5-7 newly diagnosed in men 65 years and older was excellent (mortality risk of prostate cancer over 15 years of 5.7%), whereas in men with prostate cancer T1c Gleason 8-10, there was significant risk of death from prostate cancer (22%).

Surgery

The removal of the entire prostate and urethra that crosses the prostate and attached seminal vesicles is called radical prostatectomy. There are a variety of approaches available to perform this procedure. The type of approach may vary depending on the preferences of your surgeon, your physique and your medical condition. Traditionally, radical prostatectomy was performed through an incision that extended below the belly button to the pubic bone or through an incision under the scrotum (perineal).

To reduce the morbidity of the procedure, laparoscopic approaches have been developed to perform a radical prostatectomy. The use of the robot to perform a laparoscopic radical prostatectomy, a robotic-assisted prostatectomy, is currently the most common method to perform a radical prostatectomy.

Compared to open radical prostatectomy, robotic-assisted laparoscopic radical prostatectomy is associated with less postoperative discomfort and a faster return to complete activity, as well as less intraoperative blood loss with comparable results in regards to urinary continence, erectile function. Radical prostatectomy is an appropriate treatment option for people with clinically localized prostate cancer that can be completely surgically removed, with a life expectancy of 10 years or more and for those who do not have any medical contraindications for surgery.

In some men, pelvic node dissection may be recommended based on the Gleason score, APE and radiological findings. It involves removing lymph nodes from the pelvis, which are common sites of spread of prostate cancer. This can be done at the time of radical prostatectomy or rarely as a separate procedure before definitive treatment.

The side effects of radical prostatectomy can have a significant impact on the quality of life. Therefore, it is essential that you discuss with your surgeon before the operation the risk of developing such side effects, as well as treatments that may occur after surgery.

Erectile dysfunction is a side effect of radical prostatectomy. The risk of developing erectile dysfunction varies according to your age, the state of erectile function before surgery and the need to eliminate one, both or none of the pelvic nerve bundles during radical prostatectomy. Pelvic nerve bundles are located on both sides of the prostate, just outside the capsule or on the outer edge of the prostate. Pelvic nerve bundles are involved in the erectile process, the ability to have an erection. Impotence, or the inability to have and maintain an erection of sufficient quality for successful sexual intercourse, can occur after a radical prostatectomy due to trauma, injury or removal of pelvic nerve bundles.

A radical conservative nerve prostatectomy may be performed in some people with low-risk prostate cancer. Even after a radical prostatectomy that preserves the nerves, there may be transient erectile dysfunction associated with reversible nerve trauma during surgery. Specialists who treat erectile dysfunction may recommend penile rehabilitation therapy in the hope of helping the nerves regain their function better and faster after radical prostatectomy.

Urinary incontinence is another risk after radical prostatectomy. Radical prostatectomy involves the removal of a portion of the urethra, which passes through the prostate. During the procedure, the urethra is sewn to the bladder. When the prostate is removed, the sphincter around the urethra can be traumatized, which helps prevent urine leakage. As with the risk of erectile dysfunction, the risk of incontinence may vary depending on your continence status before surgery, whether or not you have undergone prostate surgery (transurethral prostatectomy [RTUP]) and your Muscle function of the sphincter before surgery.

Erectile dysfunction and urinary incontinence are treatable conditions. Treatment for one or the other may include medical and/or surgical therapies. You should discuss these risks and your treatment with your surgeon before surgery.

Other risks of radical prostatectomy include infection, bleeding, discomfort and blood clots (deep vein thrombosis) and rarely death. To help prevent DVT, you may need to use special compression devices on your legs or receive a blood thinner.

Radical prostatectomy is rarely performed as a rescue procedure after the failure of another primary therapy, such as radiation therapy. The risk of complications, such as erectile dysfunction, incontinence, bleeding and narrowing, increases with rescue therapy.

Radiation Therapy

Radiation therapy, like surgical therapy, is a potentially curative treatment that uses radiation to kill cancer cells. It can be performed by external beam radiotherapy (EBRT) or the placement of radioactive seeds in the prostate (prostate brachytherapy). The options include:

EBRT

An x-ray machine uses a beam of low energy radiation to take a picture of a body part. Radiation therapy machines emit high-energy beams that can be focused very accurately to administer treatment on site. The radiation does not “burn” the cancer, but damages the DNA of the cells, which causes the death of the cancer cells. This process may take some time after radiotherapy treatments.

Radiation passes directly through the tissues during external radiation therapy. The radiotherapy used today provides very little energy to normal tissues. It just passes through them. Most of the energy can be concentrated and delivered directly to the prostate region that contains the cancer. This process minimizes damage to healthy tissue.

External radiation therapy can be administered in several ways, including 3-D CRT, IMRT, etc. External radiation therapy is routinely administered during short daily treatments, 5 days a week for several weeks. Although radiation does not remain in the body with this approach, the effect of daily fractions is cumulative. The new forms of external radiation therapy with machines, called CyberKnife, allow the treatment to be completed more quickly.

The proton beam radiotherapy technique used recently is a commonly used technique. Theoretically, you can focus more on the area to be treated. Proton beam radiotherapy is more expensive. Its side effects currently seem similar to those discussed for standard radiation therapy, with the exception of a higher incidence of gastrointestinal side effects with proton beam radiation. Studies comparing the efficacy and general results of conventional radiotherapy versus proton beam therapy are not yet complete.

External beam radiotherapy of the prostate can cause fatigue and irritation of the bladder and/or rectum. You can feel the urge to urinate frequently or defecate more frequently. You may also experience blood in urine or stools. These effects are usually temporary but may reappear or persist long after the end of treatment. Damage caused by radiation in adjacent tissues can cause skin irritation and local hair loss. The late onset of impotence may occur after radiotherapy due to its effect on normal tissues, including nerves adjacent to the prostate. Radiation therapy can be administered alone or in combination with hormonal therapy, which can also reduce the prostate, thereby reducing the size of the radiation area or the field to be treated.

The NCCN guidelines recommend that patients with high and very high risk prostate cancer receive neoadjuvant/concomitant/ adjuvant hormone therapy (androgen deprivation therapy [ADT]) for two or three years if the patient’s general health allows it and that patients with intermediate risk prostate cancer, they are considered for 4 to 6 months of neoadjuvant/concomitant/adjuvant (ADT) hormone therapy. Radiation therapy of the pelvic lymph nodes can be considered in patients with a high or very high risk of prostate cancer. Patients with low-risk prostate cancer should not receive ADT or lymph node radiotherapy.

Radiation therapy, like surgical therapy, is a potentially curative treatment that uses radiation to kill cancer cells. It can be performed via external beam radiation therapy (EBRT) or placement of radioactive seeds in the prostate (brachytherapy of the prostate).

Additionally, external radiotherapy is appropriate for men who are candidates for radical prostatectomy but who do not wish to undergo surgery or who are not ideal candidates for surgery.

Again, external beam radiation can also be used to treat recurrent prostate cancer located in the prostate bed (where the prostate was before surgical extraction). It is also used to treat bone metastases (spread of prostate cancer to the bone) to reduce pain or if cancer is pressuring important structures, including the spinal cord.

Brachytherapy refers to the use of radiation sources – sometimes called seeds – placed in the prostate. Brachytherapy can be performed with a technique called low dose rate (LDR) or high dose technique (HDR). In LDR brachytherapy, types of radioactive seeds, which only briefly emit a form of radiation that does not move very far into the tissues, are permanently implanted in the prostate.

High dose rate brachytherapy (HDR) involves the temporary placement of different types of seeds or sources that emit larger amounts of more penetrating radiation. These seeds administer higher doses of radiation for longer periods and can not be left in the body. These sources are placed in the prostate through surgically implanted tubes. These HDR sources are removed with the tubes in a few days.

In LDR brachytherapy, the seeds are placed in the operating room using image guidance to ensure that the seeds are placed in the right places – 40 to 100 seeds can be placed. With LDR, you can go home shortly after you wake up after the procedure. In HDR, you have to stay in the hospital for a few days. If the prostate is large, hormone therapy (ADT) can be used to shrink it before brachytherapy. The combination of Brachytherapy with external beam radiotherapy may be applicable to further increase the dose of radiation therapy to the prostate.

Brachytherapy can cause blood in the urine or sperm. This can cause a sensation similar to constipation due to swelling of the prostate. Transient urination disorders, called urinary retention, related to swelling of the prostate may also occur, which may require short-term catheter placement. It can also make you feel like you want to move your bowels more often. There may be long-term problems with rectal irritation, difficulty urinating due to scar tissue formation and even delayed impotence.

NCCN version 2.2017 guidelines indicate that brachytherapy can be used as monotherapy in patients with low risk cancers and in the selection of people with low volume intermediate risk cancers. Combination of brachytherapy and EBRT +/- 4-6 months of neoadjuvant, concomitant/adjuvant ADT can treat intermediate risk prostate cancer.

You can treat High-risk patients with a combination of EBRT and brachytherapy +/- 2-3 years of neoadjuvant/concomitant ADT/adjuvant.

Patients with a very large prostate or a very small prostate, those with symptoms of bladder obstruction or who have previously had transurethral resection of the prostate (TURP) are more difficult to treat and have a higher risk of adverse effects.

You can use brachytherapy rescue therapy for recurrent/persistent prostate cancer after external beam radiotherapy. The risk of side effects increases when you use it in rescue therapy.

Advanced Prostate Cancer

As cancer develops, it can spread throughout the body. If it spreads or returns after remission, treatment options will change.

The options include:

Chemotherapy

It can kill cancer cells throughout the body, but it can have side effects.

Chemotherapy for prostate cancer involves the use of medications in the form of tablets or injection into the veins, which can kill or at least slow the growth of metastatic cancer cells from prostate cancer. Currently, it does not play any role in the treatment of early stage prostate cancer, except in clinical trials/research studies. The use of chemotherapy in metastatic prostate cancer is currently not a potentially curative treatment, but it can relieve the symptoms of prostate cancer and prolong life. It is often used in the setting of CRPC, castration- (medical or surgical) resistant prostate cancer.

Chemotherapy drugs work in different ways. These medications can damage the DNA of cancer cells or alter the ability of cells to divide (mitosis). These effects can cause cell death. Not all prostate cancer cells are sensitive to these medications, but some may be. A tumor (a mass of cancer cells) will be reduced if more cells are destroyed and removed than they continue to grow and divide. As many normal body tissues also experience the same growth and mitosis patterns, these medications have many side effects due to their effects on normal tissues.

The active chemotherapy medications used in the treatment of prostate cancer include:

• Taxotere (Docetaxel): first-line chemotherapy option
• Carbazitaxel (Jevtana): option for people who have failed docetaxel
• Mitoxantrone (Novantrone)

Although traditionally recommended in men with castration-resistant prostate cancer, the NCCN has recommended the use of docetaxel in combination with ADT and RBE in men with prostate cancer located at very high or very high risk.

When these types of medications are given to patients with prostate cancer, they can help reduce pain and tumors. Patients who respond to these medications often live longer than those who do not respond.

Hormone Therapy

Androgens are male hormones. The main androgens are testosterone and dihydrotestosterone. Blocking or reducing these hormones seems to stop or slow the growth of cancer cells. One option is to undergo surgery to remove the testicles, which produce most of the body’s hormones. Several medications can also help.

Prostate cancer is very sensitive and depends on the level of testosterone, the male hormone, which promotes the growth of prostate cancer cells in all forms of prostate cancer, with the exception of very high grade cancers. Testosterone belongs to a family of hormones called androgens. Today, the first-line hormonal therapy against advanced and metastatic prostate cancer is called androgen deprivation therapy.

In the past, this was achieved by surgical castration called bilateral orchiectomy. In this procedure, both testicles were removed. Today, doctors can block the functioning of the testes in a controllable and more reversible way with drugs that prevent the production of testosterone (medical castration). These agents can cause prostate contraction, stop the growth of prostate cancer cells for several years and relieve the pain caused by prostate cancer that has spread or metastasized to the bones by reducing prostate cancer.

The use of ADT does not produce a cure. Over time, prostate cancer cells will develop a growth capacity despite the lack of hormones (resistance to castration). Another form of hormone therapy is the use of androgen receptor blockers. These drugs prevent testosterone from binding to and being absorbed by the prostate cancer cell, where it can help the cell survive and grow.

Currently, hormone therapy is primarily used in the treatment of locally advanced and metastatic prostate cancer. It can be used with primary healing therapies to increase the incidence of neoadjuvant therapy and adjuvant therapy. However, the primary role of ADT is in the treatment of extensive or metastatic prostate cancer.

Today, the medication that blocks the production of testes include

• LH-RH agonists: leuprolide (Lupron), goserelin (Zoladex), histrelin (Suprelin LA) and triptorelin (Trelstar) are examples of these medications. These are given through an injection in the muscle or under the skin at varying intervals of one month or more.
• LH-RH Antagonists: Degarelix (Firmagon) is a monthly injection administered under the skin.

Drugs that block the actions of testosterone include androgen receptor blockers.

• Flutamide (Eulexin), bicalutamide (Casodex), nilutamide (Nilandron) and an even more effective form known as enzalutamide (Xtandi): It is advisable to use Xtandi only in patients with castrate-resistant prostate cancer (cancer prostate refractory to traditional ADT treatment), including those with and without metastases. Xtandi is different from other androgen receptor blockers because it has three mechanism of operations. First, it prevents androgens (testosterone) from binding to the androgen receptor. Secondly, it prevents the androgen receptor from moving to the central zone (nucleus) of the cell and lastly, prevents the androgen receptor from binding with the DNA and thus, stimulating growth. The most common side effects of Xtandi are tiredness, backache, loss of appetite, constipation, arthralgia, diarrhea, hot flushes, upper respiratory tract infection, swelling of the legs, difficulty breathing, sore throat head, hypertension, vertigo, and weight loss. Less commonly observed side effects are convulsive seizures and posterior reversible encephalopathy syndrome characterized by seizures, headache, lethargy, confusion, and blindness may occur.

Surgical and medical castration leads to impotence. They also cause hot flashes, fatigue, anemia, and bone thinning (osteoporosis) over time. You may take these drugs individually or in combination with an androgen receptor blocker. The name of this procedure is combined androgen blockade.

Lupron is a type of hormonal treatment that doctors use to treat prostate cancer.

Research shows that most doctors do not recommend surgery in the later stages because it does not treat cancer that has spread to other parts of the body. However, some experts have suggested that this could be useful in some cases.

There are new treatments available for handling cases of prostate cancer. Some newer approaches aim to treat it without the side effects that other treatments can bring.

These include:

Cryotherapy

Cryotherapy is a minimally invasive therapy that damages tissue by local freezing.

The use of Cryotherapy is often as rescue therapy after failure of radiotherapy. In outpatients, hollow needles are placed in the prostate through the perineum under image guidance. Gas is passed through the needles to freeze the prostate. The hot liquid passes into the urethra at the same time to protect it. The needles are removed after the procedure. Although potentially effective, side effects can be significant and include pain and inability to urinate. Possible long-term effects include tissue damage in the areas of needle insertion, impotence, and incontinence. It is not advisable to use cryotherapy as a primary treatment for prostate cancer.

High Intensity Focused Ultrasound

High Intensity Focused Ultrasound (HIFU) is a therapeutic approach currently approved for use in Europe and is still undergoing study in the US. It uses high intensity sound waves focused on the prostate gland to heat and eventually kill cancer cells. It should only be used as part of a study (a clinical trial). The safety, side effects and comparative effectiveness of surgery and radiotherapy must be established.

Effects on Fertility

The prostate plays a role in sexual reproduction. Prostate cancer and many of its treatments affect fertility in many ways.

For example, if a man undergoes surgery to remove the prostate or testicles, this will affect sperm production and fertility.

Additionally, radiation can affect prostate tissue, damage sperm and reduce the amount of sperm needed for transport.

Hormonal treatment can also affect fertility.

However, some options to preserve these features include:

• Sperm bank before surgery
• Extract sperm directly from the testicles for artificial insemination

However, there is no guarantee that fertility will remain intact after treatment for prostate cancer. Anyone wishing to have children after treatment should discuss fertility options with their doctor when designing their treatment plan.

General Overview

Men with early prostate cancer are likely to benefit from effective treatment and survival.

According to previous statistics, the ACS expects the following percentages of people to survive an average of at least 5 years after diagnosis:

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

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

With treatment, the overall 5-year survival rate for prostate cancer is 98%. However, many people live longer than that.

The best way to detect prostate cancer at an early stage is to attend regular screenings. Anyone who has not yet attended the evaluation should consult their doctor about the options.

Specialists Who Identify and Treat Prostate Cancer

Several types of specialists identify and treat prostate cancer.

1. The primary provider (PCP) may be the first doctor to talk about prostate cancer screening and/or show concern about the risk of someone having this cancer (because of abnormal rectal examination and/or elevated PSA and/or family history of prostate cancer [brother, father or multiple relatives diagnosed with this cancer at less than 60 years of age]) during usual evaluations or because of symptoms and then refer you to a urologist for further examination.
2. Urologists are the specialists who will initially participate in the diagnosis of prostate cancer and who will perform the prostate biopsy. Depending on the grade and stage of the cancer at the time of diagnosis, additional specialists may be involved in your care. Urologists perform surgical treatments for prostate cancer (radical prostatectomy), minimally invasive treatments (cryotherapy, brachytherapy) and prescribe medications (hormonal therapy).
3. Medical oncologists are doctors who specialize in cancer treatment. Medical oncologists treat prostate cancer with a variety of medical treatments that include chemotherapy, immune system/vaccine, and hormonal therapy.
4. Radiotherapist oncologists are specialists who treat cancer with ionizing radiation. The administration of this radiation can be externally (external radiotherapy) or internally by placing small radioactive granules in the prostate (brachytherapy).
5. Often, urologists, medical oncologists, and radiation oncologists work together in a multidisciplinary team to review your case and may meet with one, two or all of these doctors at some time during your cancer treatment.

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