Prostate Cancer – Advanced: Symptoms, Diagnosis & Treatment ...

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What is Advanced Prostate Cancer?
When prostate cancer spreads beyond the prostate or returns after treatment, it is often called advanced prostate cancer.
Prostate cancer is often grouped into four stages, with stages III and IV being more advanced prostate cancer.
Early Stage | Stages I & II: The tumor has not spread beyond the prostate.
Locally Advanced | Stage III: Cancer has spread outside the prostate but only to nearby tissues.
Advanced | Stage IV: Cancer has spread outside the prostate to other parts such as the lymph nodes, bones, liver or lungs.
When an early stage prostate cancer is found, it may be treated or placed on surveillance (watching closely). Advanced prostate cancer is not “curable,” but there are many ways to treat it. Treatment can help slow advanced prostate cancer progression.
There are several types of advanced prostate cancer, including:
Biochemical Recurrence
With biochemical recurrence, the prostate-specific antigen (PSA) level has risen after treatment(s) using surgery or radiation, with no other sign of cancer.
Castration-Resistant Prostate Cancer (CRPC)
Castration-resistant prostate cancer (CRPC) is a form of advanced prostate cancer. CRPC means the prostate cancer is growing or spreading even though testosterone levels are low from hormone therapy. Hormone therapy is also called testosterone depleting therapy or androgen deprivation treatment (ADT) and can help lower your natural testosterone level. It is given through medicine or surgery to most men with prostate cancer to reduce the testosterone “fuel” that makes this cancer grow. That fuel includes male hormones or androgens (like testosterone). Typically, prostate cancer growth slows down with hormone therapy, at least for some time. If the cancer cells begin to "outsmart" hormone treatment, they can grow even without testosterone. If this happens, the prostate cancer is considered CRPC.
Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC)
Prostate cancer that no longer responds to hormone treatment and is only found in the prostate. This is found by a rise in the PSA level, while the testosterone level stays low. Imaging tests do not show signs the cancer has spread.
Metastatic Prostate Cancer
Cancer cells have spread beyond the prostate. Cancer spread may be seen on imaging studies and may show the cancer has spread. Prostate cancer is metastatic if it has spread to these areas:
Lymph nodes outside the pelvis
Bones
Other organs, such as liver or lungs
You may be diagnosed with metastatic prostate cancer when you are first diagnosed, after having completed your first treatment or even many years later. It is uncommon to be diagnosed with metastatic prostate cancer on first diagnosis, but it does happen.
Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
Metastatic hormone-sensitive prostate cancer (mHSPC) is when cancer has spread past the prostate into the body and is responsive to hormone therapy or the patient has not yet had hormone therapy. This means that levels of male sex hormones, including androgens like testosterone, can be reduced to slow cancer growth. Unchecked, these male sex hormones “feed” the prostate cancer cells to let them grow. Hormone therapy, like ADT, may be used to reduce the levels of these hormones.
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Metastatic castration-resistant prostate cancer is when cancer has spread past the prostate into the body and it is able to grow and spread even after treatments were used to lower testosterone levels. The PSA levels keep rising and metastatic spots are present/growing. This is disease progression despite medical or surgical castration.
Symptoms
Men with advanced prostate cancer may or may not have any signs of sickness. Symptoms depend on the size of new growth and where the cancer has spread in the body. With advanced disease, mainly if you have not had treatment to the prostate itself, you may have problems passing urine or see blood in your urine. Some men may feel tired, weak or lose weight. When prostate cancer spreads to bones, you may have bone pain. Tell your doctor and nurse about any pain or other symptoms you feel. There are treatments that can help.
Risks
Your risks for prostate cancer rise if you are age 65 or older, have a family history of prostate cancer, are African American or have inherited mutations of the BRCA1 or BRCA2 genes.
Age: For all men, prostate cancer risk increases with age. About 6 in 10 cases of prostate cancer are found in men older than 65. Prostate cancer is rare in men under the age of 40.
Race/Ethnicity: African American men and Caribbean men of African ancestry face a higher risk for being diagnosed with prostate cancer. They are also more likely to be diagnosed with prostate cancer at younger ages. It is not clear why prostate cancer affects African American men more than other racial/ethnic groups.
Genetic Factors: The risk of prostate cancer more than doubles in men with a family history of prostate cancer in their grandfathers, fathers or brothers. Having family members with breast and ovarian cancer also raises a man’s risk for prostate cancer. That is because breast, ovarian and prostate cancers share some of the same genes, including BRCA1 and BRCA2.If a person has any of these mutations, they should be screened earlier or more often for prostate cancer. As a health care tool, genetic test results can help determine whether a certain treatment would be helpful. For example, men with an inherited poly- (ADP)-ribose polymerase (PARP) mutation in the DNA of cancer cells could be helped with a PARP inhibitor. This targeted therapy inhibits the PARP mutation and helps stop it from repairing cancer cells. Your doctor may suggest genetic testing because of family history or because you have an aggressive prostate cancer. Genetic testing looks for certain inherited changes (mutations) in a person’s genes and can help find out if a cancer is hereditary. To find out if you have a genetic mutation linked to prostate cancer, you may take a simple blood or saliva test.
Diagnosis
Advanced cancer may be found before, at the same time or later than the main tumor. Most men diagnosed with advanced prostate cancer have had biopsy and treatment in the past. When a new tumor is found in someone who has been treated for cancer in the past, usually cancer has spread. Even if you have already been diagnosed with prostate cancer, your health care provider may want to observe changes over time. The following tests are used to diagnose and track prostate cancer:
Blood Tests
The PSA blood test measures a protein in your blood called the prostate-specific antigen (PSA). Only the prostate and prostate cancers make PSA. Results for this test are usually shared as nanograms of PSA per milliliter (ng/mL) of blood. The PSA test is used to look for changes to the way your prostate produces PSA. It is used to stage cancer, plan treatment and track how well treatment is going. A rapid rise in PSA may be a sign something is wrong. In addition, your doctor may want to test the level of testosterone in your blood.
Advanced cancer may be found before, at the same time, or later than the main tumor. Most men diagnosed with advanced prostate cancer have had biopsy and treatment in the past. When a new tumor is found in someone who has been treated for cancer in the past, usually cancer has spread.
Digital Rectal Exam (DRE)
The Digital Rectal Exam (DRE) is a physical exam used to help your doctor feel for changes in your prostate. This test is also used to screen for and stage cancer, or track how well treatment is going. During this test, the doctor feels for an abnormal shape, consistency, nodularity or thickness to the gland. The DRE is often done with the PSA together. For this exam, the health care provider puts a lubricated gloved finger into the rectum.
Imaging and Scans
Imaging helps doctors learn more about your cancer. Some types are:
Magnetic resonance imaging (MRI): An MRI scan can give a very clear picture of the prostate and show if the cancer has spread into the seminal vesicles or nearby tissue. A contrast dye is often injected into a vein before the scan to see details. MRI scans use radio waves and strong magnets instead of x-rays.
Computed tomography (CT) scan: The CT scan is used to see cross-sectional views of tissue and organs. It combines x-rays and computer calculations for detailed images from different angles. It can show solid vs. liquid structures, so it is used to diagnose masses in the urinary tract. CT scans are not always as useful as MRI to see the prostate gland itself, but are very good at evaluating surrounding tissues and structures.
Bone scan: A bone scan can help show if cancer has reached the bones. If prostate cancer spreads to distant sites, it often goes to the bones first. In these studies, a radionuclide dye is injected into the body. Over a few hours, images are taken of the bones. The dye helps to make images of cancer show up more clearly.
Positron emission tomography (PET) scan: The PET scan may help your doctor better see where and how much the cancer is growing. A special drug (called a tracer) is given through your vein, or you may inhale or swallow the drug. Your cells will pick up the tracer as it passes through your body. The scanner allows your doctor to better see where and how much the cancer is growing.
Biopsy
Men diagnosed with advanced prostate cancer from the beginning may start with a prostate biopsy. It is also used to grade and stage the cancer. Most men diagnosed with advanced prostate cancer have had a prostate biopsy in the past. When a new tumor is found in someone who has been treated before, it is usually cancer that has spread.
A biopsy is a tissue sample taken from your prostate or other organs to look for cancer cells. There are many approaches to prostate biopsies. These can be done through a probe placed in the rectum, through the skin of the perineum (already between the scrotum and rectum) and may use a specialized imaging device, such as MRI. The biopsy removes small pieces of tissue for review under a microscope. The biopsy takes 10 to 20 minutes. A pathologist (a doctor who classifies disease) looks for cancer cells within the samples. If cancer is seen, the pathologist will "grade" the tumor.
Grading and Staging
Prostate cancer is grouped into four stages. The stages are defined by how much and how quickly the cancer cells are growing. The stages are defined by the Gleason Score and the T (tumor), N (node), M (metastasis) Score.
Gleason Score
If a biopsy finds cancer, the pathologist gives it a grade. The most common grading system is called the Gleason grading system. The Gleason score is a measure of how quickly the cancer cells can grow and affect other tissue. Biopsy samples are taken from the prostate and given a Gleason Grade by a pathologist. Lower grades are given to samples with small, closely packed cells. Higher grades are given to samples with more spread out cells. The Gleason Score is set by adding together the two most common grades found in a biopsy sample.
The Gleason score will help your doctor understand if the cancer is as a low-, intermediate- or high-risk disease. The risk assessment is the risk of recurrence after treatment. Generally, Gleason scores of 6 are treated as low risk cancers. Gleason scores of around 7 are treated as intermediate/mid-level cancers. Gleason scores of 8 and above are treated as high-risk cancers. Some of these high-risk tumors may have already spread by the time they are found.
Staging
The Tumor, Nodes and Metastasis (TNM) is the system used for tumor staging. The T, N, M score is a measure of how far the prostate cancer has spread in the body. The T (tumor) score rates the size and extent of the original tumor. The N (nodes) score rates whether the cancer has spread into nearby lymph nodes. The M (metastasis) score rates whether the cancer has spread to distant sites.
Tumors found only in the prostate are more successfully treated than those that have metastasized (spread) outside the prostate. Tumors that have metastasized are incurable and require drug based therapies to treat the whole body.
Prostate Cancer Stage Groupings
Prostate cancer is staged as:
T1: Health care provider cannot feel the tumor
T1a: Cancer present in less than 5% of the tissue removed and low grade (Gleason less than 6)
T1b: Cancer present in more than 5% of the tissue removed or is of a higher grade (Gleason greater than 6)
T1c: Cancer found by needle biopsy done because of a high PSA
T2: Health care provider can feel the tumor with a DRE but the tumor is confined to prostate
T2a: Cancer found in one half or less of one side (left or right) of the prostate
T2b: Cancer found in more than half of one side (left or right) of the prostate
T2c: Cancer found in both sides of the prostate
T3: Cancer has begun to spread outside the prostate and may involve the seminal vesicles
T3a: Cancer extends outside the prostate but not to the seminal vesicles
T3b: Cancer has spread to the seminal vesicles
T4: Cancer has spread to nearby organs
N0: There is no sign of the cancer moving to the lymph nodes in the area of the prostate (becomes N1 if cancer has spread to lymph nodes)
M0: There is no sign of tumor metastasis (becomes M1 if cancer has spread to other parts of the body)
Treatment
The goal of advanced prostate cancer treatment is to shrink or control tumor growth and control symptoms. There are many treatment choices for advanced prostate cancer. Which treatment to use, and when, will depend on discussions with your doctor. It is best to talk to your doctor about how to handle side effects before you choose a plan.
Treatment options include:
Hormone Therapy
Chemotherapy
Immunotherapy
Combination Therapy
Bone-targeted Therapy
Radiation
Active Surveillance
Clinical Trials
What is Hormone Therapy?
Hormone therapy is a treatment that lowers a man's testosterone, or hormone, levels. This therapy is also called ADT. Testosterone, an important male sex hormone, is the main fuel for prostate cancer cells, so reducing its levels may slow the growth of those cells. Hormone therapy may help slow prostate cancer growth in men when prostate cancer has metastasized (spread) away from the prostate or returned after other treatments. Some treatments may be used to shrink or control a local tumor that has not spread. There are several types of hormone therapy for prostate cancer treatment, including medications and surgery. Your doctor may prescribe a variety of therapies over time.
Hormone Therapy with Surgery
Surgery to remove the testicles for hormone therapy is called orchiectomy or castration. When the testicles are removed, it stops the body from making the hormones that fuel prostate cancer. It is rarely used as a treatment choice in the United States. Men who choose this therapy want a one-time surgical treatment. They must be willing to have their testicles permanently removed and must be healthy enough to have surgery.
This surgery allows the patient to go home the same day. The surgeon makes a small cut in the scrotum (sac that holds the testicles). The testicles are detached from blood vessels and removed. The vas deferens (tube that carries sperm to the prostate before ejaculation) is detached. Then the sac is sewn up.
There are multiple benefits to undergoing orchiectomy to treat advanced prostate cancer. It is not expensive. It is simple and has few risks. It only needs to be performed once. It is effective right away. Testosterone levels drop dramatically.
Side effects to your body include infection and bleeding. Removing the testicles means the body stops making testosterone, so there is also a chance of the side effects listed below for hormone therapy. Other side effects of this surgery may be about body image due to the look of the genital area after surgery. Some men choose to have artificial testicles or saline implants placed in the scrotum to help the scrotum look the same as before surgery. Some men choose another surgery called subcapsular orchiectomy. This removes the glands inside the testicles, but it leaves the testicles themselves, so the scrotum looks normal.
Hormone Therapy with Medications
There are different types of hormone therapy available as injections or as pills that can be taken by mouth. Some of these therapies stop the body from producing luteinizing-hormone-releasing-hormone (LHRH, also called gonadotrophin releasing hormone, or GnRH). LHRH triggers the body to make testosterone. Other therapies stop prostate cells from being affected by testosterone by blocking hormone receptors. Sometimes, after the first shot, a blood test is done. This is done to check testosterone levels. You may also have tests to monitor your bone density during treatment.
With LHRH treatment there is no need for surgery. Candidates for this treatment include men who cannot or do not wish to have surgery to remove their testicles.
There are different types of medical hormone therapy your doctor could prescribe to lower your body's production of testosterone. After your testosterone levels drop to a very low level, you are at "castration level." Once testosterone levels drop, prostate cancer cells may decrease in growth and proliferation.
Types of Medications
Agonists (analogs)
LHRH/GnRH agonists are drugs that lower testosterone levels. They may be used for cancer that has come back, whether or not it has spread.
When first given, agonists cause the body to produce a burst of testosterone (called a "flare"). Agonists are longer acting than natural LHRH. After the initial flare, the drug tricks your brain into thinking it does not need to produce LHRH/GnRH because it has enough. As a result, the testicles are not stimulated to produce testosterone.
LHRH or GnRH agonists are given as shots or as small pellets placed under the skin. Based on the drug used, they could be given from once every one, three or six months.
Antagonists
These drugs also lower testosterone. Instead of flooding the pituitary gland with LHRH, they stop LHRH from binding to receptors. There is no testosterone flare with an LHRH/GnRH antagonist because the body does not get the signal to produce testosterone.
Antagonists may be taken by mouth or injected (shot) under the skin, in the buttocks or abdomen. The shot is given in the health care provider's office. You will likely stay in the office awhile after the shot to ensure there is no allergic reaction. After the first shot, a blood test makes sure testosterone levels have dropped. You may also have tests to monitor bone density.
Anti-androgen drugs
Antiandrogen drugs are taken as a pill by mouth. This therapy depends partly on where the cancer has spread and its effects.
This treatment lowers testosterone by inhibiting the androgen receptors in the prostate cancer cells. Normally, testosterone would bind with these receptors to fuel growth of prostate cancer cells. With the receptors blocked, testosterone cannot "feed" the prostate. Using anti-androgens a few weeks before, or during, LHRH therapy may reduce "flare ups." Antiandrogens may also be used after surgery or castration when hormone therapy stops working.
CAB (combined androgen reducing treatment, with anti-androgens)
This method blends castration (by surgery or with the drugs described above) and antiandrogen drugs. The treatment reduces production of testosterone and can help stop it from binding to cancer cells.
Surgery or taking oral drugs may be ways to lower the testosterone made by your testicles. The rest of the testosterone is made by the adrenal glands. Antiandrogen therapy blocks testosterone made by the adrenal glands.
Androgen synthesis inhibitors
These drugs help stop other parts of your body (and the cancer itself) from making more testosterone and its metabolites. Men newly diagnosed with metastatic hormone sensitive prostate cancer (mHSPC) or men with metastatic castration-resistant prostate cancer (mCRPC) may be good candidates for this therapy.
Androgen synthesis inhibitors may be taken by mouth as a pill. This drug helps stop your body from releasing the enzyme needed to make androgens in the adrenal glands, testicles and prostate tissue, resulting in reduced levels of testosterone and other androgens. Because of the way it works, this drug must be taken with an oral steroid.
Hormone Therapy Side Effects
Unfortunately, hormone therapy may not work forever, and it does not cure the cancer. Over time, the cancer may grow in spite of the low hormone level. Other treatments are also needed to manage the cancer.
Hormone therapies have many possible side effects. Learn what they are. Intermittent (not constant) hormone therapy may also be a treatment option. Before starting any type of hormone therapy, talk with your health care provider.
Possible hormone therapy side effects include:
Lower libido (sexual desire) in most men
Erectile dysfunction, the inability to have or keep a strong enough erection for sex
Hot flashes or sudden spread of warmth to the face, neck and upper body, heavy sweating
There are many benefits and risks to each type of hormone therapy, so ask questions of your doctor so you understand what is best for you.
What is Chemotherapy?
Chemotherapy drugs can slow the growth of cancer. These drugs may reduce symptoms and extend life. Or they may ease pain and symptoms by shrinking tumors. Chemotherapy is useful for men whose cancer has spread to other parts of the body.
Most chemotherapy drugs are given through a vein (intravenous, IV). During chemotherapy, the drugs move throughout the body. They kill quickly growing cancer cells and non-cancer cells. Often, chemotherapy is not the main therapy for prostate cancer. But it may be a treatment option for men whose cancer has spread. Chemotherapy may be given before pain starts as it may prevent pain as cancer spreads to bones and other sites.
Side effects may include hair loss, fatigue, nausea and vomiting. There may be changes in your sense of taste and touch. You may be more prone to infections. You may experience neuropathy (tingling or numbness in the hands and feet). Due to the side effects from chemotherapy, the decision to use these drugs may be based on:
Your health and how well you can tolerate the drug
What other treatments you have tried
If radiation is needed to relieve pain quickly
What other treatments or clinical trials are available
Your treatment goals
If you use chemotherapy, your health care team may watch you closely to manage side effects. There are medicines to help with things like nausea. Most side effects stop once chemotherapy ends.
What is Immunotherapy?
Immunotherapy uses the body’s immune system to fight cancer. It may be a choice for men with mCRPC who have no symptoms or only mild symptoms.
If the cancer returns and spreads, your doctor may offer a cancer vaccine to boost your immune system so it can attack the cancer cells. Immunotherapy may be given to mCRPC patients before chemotherapy or it may be used along with chemotherapy.
Side effects are often in the first 24 hours after treatment and may include fever, chills, weakness, headache, nausea, vomiting and diarrhea. Patients may also have low blood pressure and rashes.
What is Combination Therapy?
Side effects are often in the first 24 hours after treatment and may include fever, chills, weakness, headache, nausea, vomiting and diarrhea. Patients may also have low blood pressure and rashes.
What is Bone-targeted Therapy?
Bone-targeted therapy may help men with prostate cancer that has spread to the bones as they may get “skeletal-related events” (SREs). SREs include fractures, pain and other problems. If you have advanced prostate cancer or are taking hormone therapy, your provider may suggest calcium, Vitamin D or other drugs for your bones. These drugs may stop the cancer, reduce SRE’s and help prevent pain and weakness from cancer growing in your bones.
Radiopharmaceuticals are drugs with radioactivity. They can be used to help with bone pain from metastatic cancer. Some may also be used for men whose mCRPC has spread to their bones. They may be offered when ADT is not working. Radiopharmaceuticals give off small amounts of radiation that go to the exact parts where cancer cells are growing.
Drugs used to reduce SREs may help reduce bone turnover. Side effects include low calcium, worsening kidney function and, rarely, destruction of the jawbone.
Calcium and Vitamin D are also used to help protect your bones. They are often recommended for men on hormone therapy to treat prostate cancer.
What is Radiation Therapy?
Radiation uses high-energy beams to kill tumors. Prostate cancer often spreads to the bones. Radiation can help ease pain or prevent fractures caused by cancer spreading to the bone.
There are many types of radiation treatments. Radiation may be given once or over several visits. Treatment is like having an x-ray. It uses high-energy beams to kill tumors. Some radiation techniques focus on saving nearby healthy tissue. Computers and software allows better planning and targeting of radiation doses. They target the radiation to pinpoint where it is needed.
Active Surveillance for Prostate Cancer
Active surveillance is mainly used to delay or avoid aggressive therapy. It is often used if you have a small, slow growing cancer. It may be a choice for men who do not have symptoms or want to avoid sexual, urinary or bowel side effects for as long as possible. Others may choose surveillance due to their age or overall health.
This method may require you to have many tests over time to track cancer growth. This lets your doctor know how things are going, and prevents treatment-related side effects. This will also help you and your health care team focus on managing cancer-related symptoms. Talk with your care team about whether this is a good choice for you.
Clinical Trials
Clinical trials are research studies that test new treatments or learn how to use existing treatments better. Clinical studies aim to find the treatment strategies that work best for certain illnesses or groups of people. For some patients, taking part in a clinical trial may be a treatment option.
Clinical trials follow strict scientific standards. These standards protect patients and help produce reliable study results. You will be given either a standard treatment or the treatment being tested. All of the approved treatments used to treat or cure cancer began in a clinical trial.
It is of great value to learn about the risks and benefits of the treatment being studied.
Other Considerations
Follow-Up Care
You and your doctor may schedule office visits for tests and follow-up over time. There are certain symptoms your doctor should know about right away, such as blood in your urine or bone pain, but it is best to ask your health care team about the symptoms you should report. Some men find it helpful to keep a diary to help remember things to talk about during follow-up visits.
Incontinence is the inability to control the release of urine and can sometimes happen with prostate cancer treatment. There are different types of incontinence:
Stress Urinary Incontinence (SUI), when urine leaks with coughing, laughing, sneezing or exercising or with any additional pressure on the pelvic floor muscles. This is the most common type.
Urge Incontinence, or the sudden urge to pass urine, even when the bladder is not full, because the bladder is overly sensitive. This might be called overactive bladder (OAB).
Mixed Incontinence, a combination of stress and urge incontinence with symptoms from both types.
Because incontinence may affect your physical and emotional recovery, it is important to understand how to manage this problem. There are treatment choices that may help incontinence. Talk with your doctor before trying any of these options.
Men may have sexual health problems following their cancer diagnosis or treatments. Erectile dysfunction (ED) is when a man finds it hard to get or keep an erection strong enough for sex. ED happens when there is not enough blood flow to the penis or when nerves to the penis are harmed.
Cancer in the prostate, colon, rectum and bladder are the most common cancers that can affect a man’s sexual health. Treatments for cancer, along with emotional stress, can lead to ED.
The chance of ED after prostate cancer treatment depends on many things, such as:
Age
Overall health
Medications you take
Sexual function before treatment
Cancer stage
Damage to your nerves or blood vessels from surgery or radiation
There are treatments that may help ED. They include pills, vacuum pumps, urethral suppositories, penile injections and implants. Treatment can be individualized. Some treatments may work better for you than others. They have their own set of side effects. A health care provider can talk with you about the pros and cons of each method and help you decide which single treatment or combination of treatments is right for you.
Because prostate cancer treatment can affect your appetite, eating habits and weight, it is important to try your best to eat healthy. If you have a hard time eating well, reach out to a registered dietitian/nutritionist (RDN).There are ways to help you get the nutrition you need. Always talk with your doctor before making changes to your diet.
Exercise
Exercise may improve your physical and emotional health. It can also help you manage your weight, maintain muscle and bone strength and help manage side effects.
Always talk with your doctor before starting or changing your exercise routine. If approved by your doctor, men may want to strive to exercise about one to three hours per week. Cardiovascular exercise and strength/resistance training may be good choices. This can include walking or more intense exercise. Physical exercise may help you to:
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