PROSTATE CANCER

PROSTATE CANCER FACTS


Prostate cancer is the type of cancer found most often among men, and more than 192,000 cases are diagnosed each year. It’s second only to lung cancer as a cause of cancer deaths among men.

Chances are that you know someone who has prostate cancer or has been treated for it. 

The survival rate is increasing, and awareness, screening and improved therapies are some of the reasons. If found early, prostate cancer has a good chance for successful treatment. In fact, prostate cancer sometimes does not pose a significant threat to a man’s life and can be observed carefully instead of treated immediately.

The prostate is a walnut-size gland in the male reproductive system. Just below the bladder and in front of the rectum, it surrounds part of the urethra, a tube that empties urine from the bladder. The prostate helps produce semen and nourish sperm.

The prostate begins to develop while a baby is in his mother’s womb. Fueled by androgens (male hormones), it continues to grow until adulthood.

Sometimes, the part of the prostate around the urethra may keep growing, causing benign prostatic hyperplasia (BPH). While this condition may interfere with passing urine and needs to be treated, it is not prostate cancer.

Prostate Cancer Types

Almost all prostate cancers begin in the gland cells of the prostate and are known as adenocarcinomas.

Pre-cancerous changes of the prostate: By age 50, about half of all men have small changes in the size and shape of the cells in the prostate. This is called prostatic intraepithelial neoplasia (PIN).

If PIN is present, the best strategy is to be certain a thorough biopsy procedure shows no invasive cancer. If PIN is the only finding, then careful follow-up screening with a prostate-specific antigen (PSA) blood test and digital rectal examination (DRE) is recommended.

Prostate Cancer Risk Factors


Anything that increases your chance of getting prostate cancer is a risk factor. These include:

  • Age: This is the most important risk factor. Most men who develop prostate cancer are older than 50. About two of every      three prostate cancers are diagnosed in men older than 65.
  • Family history: Risk is higher when other members of your family (especially father, brother, son) have or had prostate        cancer, especially if they were young when they developed it.
  • Race: African-American men have nearly double the risk of prostate cancer as white men. It is found less often in Asian        American, Hispanic and American Indian men.
  • Diet: A high-fat diet, particularly a diet high in animal fats, may increase risk; diets high in fruits and vegetables may              decrease risk.
  • Nationality: Prostate cancer is more prevalent in North America and northwestern Europe than other parts of the world.



Prostate Cancer Prevention

Certain actions may help lower your risk of prostate cancer:

  • Eat at least five servings of fruits and vegetables daily and eat less red meat. Decrease fat intake.
  • Tell your doctor about supplements you take. Some of these may decrease the PSA level. A recent large study found that    selenium and vitamin E, once thought to decrease risk of prostate cancer, have no effect.
  • Exercise regularly
  • Maintain your ideal weight



Other ways to avoid prostate cancer are being investigated. These include:

  • Lycopenes: These substances found in tomatoes, pink grapefruit and watermelon may help prevent damage to cells.
  • Proscar (finasteride) or Avodart (dutesteride): If you are at high risk for prostate cancer, talk to your urologist or            other provider who is familiar with studies about these drugs.



PROSTATE CANCER SYMPTOMS


Prostate cancer often shows no symptoms in the early stages. If symptoms do appear, they vary from man to man. Signs you may have prostate cancer may include:

  • Painful or burning urination
  • Inability to urinate or difficulty in starting to urinate
  • Difficulty trying to hold back urination
  • Weak or interrupted urine flow
  • Frequent or urgent need to urinate
  • Trouble emptying the bladder completely
  • Blood in the urine or semen
  • Continual pain in the lower back, pelvis, hips or thighs
  • Difficulty having an erection



Having any of these symptoms does not mean you have prostate cancer. Some of the same symptoms can occur with BPH (benign prostatic hypertrophy) or other health problems. If you notice one or more of these symptoms for more than two weeks, see your doctor.


PROSTATE CANCER DIAGNOSIS


If you have prostate cancer, it’s important to get an accurate diagnosis as soon as possible. This helps increase the odds for successful treatment and recovery.

Prostate Cancer Diagnosis

If you have symptoms that may signal prostate cancer, your doctor will ask you questions about your health, your lifestyle and your family medical history.

One or more of the following tests may be used to find out if you have cancer and if it has spread. These tests also may be used to find out if treatment is working.

Digital Rectal Exam (DRE)

The simplest screening test for prostate cancer is the digital rectal exam (DRE). The health care provider gently inserts a gloved forefinger into the rectum to feel the prostate gland for enlargement or other abnormalities, such as a lump.

The DRE is not a definitive cancer test, but regular exams help detect changes in the prostate over time that might signal cancer or pre-cancerous conditions.

Although this test usually is not as reliable as the PSA blood test, a DRE may be able to find cancer if a man has a normal PSA level. A DRE also may be used to tell if prostate cancer has spread or returned after treatment.

Prostate-specific antigen (PSA) Test

Prostate-specific antigen (PSA) is a protein produced by the cells of the prostate gland. It is found mostly in semen, but a small amount is in the blood as well.

A blood test measures the amount of PSA circulating in the blood, expressed in nanograms per milliliter (ng/mL). This level is used to assess prostate cancer risk. A higher PSA level usually means a higher chance of having prostate cancer.

However, the test has limitations. PSA is produced by both prostate tissue and prostate cancer. Sometimes prostate cancer does not produce much PSA and higher levels can be caused by factors other than cancer, including:

  • Enlarged prostate, also called benign prostatic hyperplasia (BPH), which is found often in older men
  • Age: PSA levels normally go up slowly as men age
  • Infection or inflammation of the prostate, which also is called prostatitis
  • PSA may rise briefly after ejaculation, then return to normal levels



On the other hand, certain conditions may make PSA levels low, even when a man has prostate cancer. These include:

  • Some drugs used to treat BPH or other conditions
  • Certain herbal medicines or supplements
  • Obesity



Despite its limitations, PSA testing has helped detect prostate cancer in countless men. In 1984, before PSA testing was available, the chance of finding early prostate cancer was about 50%. In 1993, after PSA testing became widely used, that figure jumped to more than 90%.

Men with very low PSA levels may need to be tested every two years. However, if PSA is higher, the doctor may recommend more frequent testing.

Because prostate cancer develops slowly, physicians usually do not recommend the PSA test for men who are older than 75 or have other significant health issues.

Additional PSA Testing

Besides screening, PSA testing can be used in other ways in men who have been diagnosed with prostate cancer. For instance, it may:

  • Help doctors plan your treatment or further testing
  • Determine if cancer has metastasized (spread beyond the prostate)
  • Find out if treatment is working or cancer has returned
  • Aid in active surveillance (also called watchful waiting) by showing if cancer is growing



Biopsy

If your doctor suspects prostate cancer, a biopsy may be performed. This is the only way to tell for sure if you have prostate cancer.

Biopsies for prostate cancer are done in a doctor’s office or other facility as an outpatient procedure. A local anesthetic like dentists use, often lidocaine, is injected into the area close to the prostate to make the procedure more comfortable.

A small transrectal ultrasound (TRUS) probe with an imaging device is inserted into the rectum so the doctor can view the prostate on a video screen. Using this image as a guide, the physician injects a thin needle through the wall of the rectum into the prostate. Several tiny samples of tissue are removed.

Sometimes a biopsy will not find prostate cancer, even if it is there. If your doctor is concerned that you may have prostate cancer based on a follow-up PSA test, a second biopsy may be performed.

Some people have an elevated risk of developing prostate cancer. 

In rare cases, prostate cancer can be passed down from one generation to the next. Genetic counseling may be right for you.


Prostate Cancer Risk Assessment

If you are diagnosed with prostate cancer, your doctor will make a series of estimates about the risk the disease may be harmful in the future. Factors include:

  • Gleason score (see below)
  • PSA level
  • Clinical stage, which is based on findings of the digital rectal exam (DRE)



Low risk:

  • Less than 10% chance of having spread to other parts of the body
  • Low risk of progressing if not treated
  • PSA less than 10 ng/nL
  • Gleason score of 6 or lower
  • No tumor felt on DRE or feels contained within the prostate gland with only a small abnormal area



Intermediate risk:

  • 10% to 15% chance of having spread
  • Higher chance (up to 70% over 15 years) of progressing if not treated
  • PSA of 10 to 20 ng/mL
  • Gleason score of 7
  • Tumor can be felt on one or both sides of the prostate on DRE, but it seems to be contained within the gland



High risk:

  • Aggressive features that increase the chance of spreading now or in the future
  • PSA over 20 ng/mL
  • Gleason score of 8 to10
  • Tumor can be felt on DRE and seems to have spread outside the gland



Gleason Grading System​


If a biopsy finds prostate cancer, it will be classified using the Gleason grading system. This helps doctors choose the best treatment options and predict how quickly the cancer is growing.

Prostate cancer contains several types of cells. The Gleason system uses the numbers 1 to 5 to grade the most common (primary) and next most common (secondary) cell types found in a tissue sample. The sum of these two numbers is the Gleason score, which indicates how aggressive the tumor is. The higher the Gleason score, the more aggressive the cancer.

Gleason grades 1 and 2 are rarely seen since these changes are now usually classified as benign or occur at the center of the gland and remain undiscovered. That means the usual lowest grade is 3. Gleason scores of:

  • 3+3 are low grade and have the lowest risk of harm
  • 3+4 and 4+3 are intermediate risk — the latter being the more aggressive type
  • 4+4 through 5+5 are the highest risk



If the prostate cancer is determined to be intermediate or high risk, imaging tests such as bone scans and CAT (computed axial tomography) or MRI (magnetic resonance imaging) scans may be used to determine if the cancer has spread.

Taken together, the disease risk status and imaging results will help your doctor plan the best treatment.


TREATMENT


In cancer care, different types of doctors often work together to create an overall treatment plan that may combine different type of treatments. This is called a multidisciplinary team. 

Descriptions of the most common treatment options for prostate cancer are listed below, followed by an outline of general approaches to treatment according to stage. Treatment options and recommendations depend on several factors, including the type and stage of cancer, possible side effects, and the patient’s preferences and overall health. Your care plan may also include treatment for symptoms and side effects, an important part of cancer care.

 
Active Surveillance and Watchful Waiting

If prostate cancer is found at an early stage, is growing slowly, and treating the cancer would cause more discomfort than the disease, a doctor may recommend active surveillance or watchful waiting.

Active Surveillance. Because prostate cancer treatments can cause side effects, such as impotence, which is the inability to get and maintain an erection, and incontinence, the inability to control urine flow, treating prostate cancer may seriously affect a man’s quality of life. For this reason, many men with very early prostate cancer and their doctors consider postponing cancer treatment rather than starting treatment immediately. During active surveillance, the cancer is monitored closely for signs that it is worsening.

Active surveillance is usually preferred for men with a long life expectancy who may benefit from curative local therapy if the cancer shows signs of getting worse. ASCO endorses recommendations from CancerCare Ontario concerning active surveillance, which recommend active surveillance for most patients with a Gleason score of 6 or below with cancer that has not spread beyond the prostate. Sometimes, active surveillance may be an option for men with a Gleason score of 7.

ASCO encourages the following testing schedule for active surveillance:

  • A PSA test every 3 to 6 months
  • A DRE at least every year
  • Another prostate biopsy within 6 to 12 months, then a biopsy at least every 2 to 5 years
  • A patient on active surveillance should receive treatment if the cancer shows signs of becoming more aggressive or              spreading, causes pain, or blocks the urinary tract.


Watchful Waiting. Watchful waiting may be an option for much older men and those with other serious or life-threatening illnesses who are expected to live less than 5 years. With watchful waiting, routine PSA tests, DRE, and biopsies are not usually performed. If a patient develops symptoms from the prostate cancer, such as pain or blockage of the urinary tract, then treatment may be recommended. This may include ADT (see below, under Systemic treatments). Men who start out with active surveillance who later have a shorter life expectancy may switch to watchful waiting at some point to avoid repeated tests and biopsies.

Local Treatments

Local treatments get rid of cancer from a specific, limited area of the body. For men diagnosed with early-stage prostate cancer, local treatments, such as surgery or radiation therapy, may get rid of the cancer completely. However, if the cancer has spread outside the prostate gland, other types of treatment may be needed to destroy cancer cells located in other parts of the body.

Surgery

Surgery is the removal of the tumor and some surrounding healthy tissue during an operation. It is used to try to eliminate a tumor before it spreads outside the prostate. A surgical oncologist is a doctor who specializes in treating cancer using surgery. For prostate cancer, an urologist or urologic oncologist is the surgical oncologist involved in treatment. The type of surgery depends on the stage of the disease, the man’s overall health, and other factors.

Surgical options include:

Radical (open) prostatectomy. A radical prostatectomy is the surgical removal of the entire prostate and the seminal vesicles. Lymph nodes in the pelvic area may also be removed. This operation has the risk of interfering with sexual function. Nerve-sparing surgery, when possible, increases the chance that a man can maintain his sexual function after surgery by avoiding surgical damage to the nerves that allow erections and orgasm to occur. Orgasm can occur even if some nerves are cut since these are 2 separate processes.Urinary incontinence is also a possible side effect of radical prostatectomy. To help resume normal sexual function, men can receive drugs, penile implants, or injections. Sometimes, another surgery can fix urinary incontinence.

Robotic or laparoscopic prostatectomy. This type of surgery is possibly much less invasive than a radical prostatectomy and may shorten recovery time. A camera and instruments are inserted through small, keyhole incisions in the patient’s abdomen. The surgeon then directs the robotic instruments to remove the prostate gland and some surrounding healthy tissue. In general, robotic prostatectomy causes less bleeding and less pain, but the sexual and urinary side effects can be similar to a radical (open) prostatectomy. It is comparable to open prostatectomy. 

Cryosurgery. Cryosurgery, also called cryotherapy or cryoablation, is the freezing of cancer cells with a metal probe inserted through a small incision in the area between the rectum and the scrotum, the skin sac that contains the testicles. It is not an established therapy or standard of care for men newly diagnosed with prostate cancer. Cryosurgery has not been compared with radical prostatectomy or radiation therapy, so doctors do not know if it is a comparable treatment option. Its effects on urinary and sexual function are also not well defined.


Radiation Therapy

Radiation therapy is the use of high-energy rays to destroy cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. A radiation therapy regimen (schedule) usually consists of a specific number of treatments given over a set period of time.

The types of radiation therapy used to treat prostate cancer include:

External-beam radiation therapy. External-beam radiation therapy is the most common type of radiation treatment. The radiation oncologist uses a machine located outside the body to focus a beam of x-rays on the area with the cancer. Some cancer centers use conformal radiation therapy (CRT), in which computers help precisely map the location and shape of the cancer. CRT reduces radiation damage to healthy tissues and organs around the tumor by directing the radiation therapy beam from different directions to focus the dose on the tumor.

Intensity-modulated radiation therapy (IMRT). IMRT is a type of external-beam radiation therapy that uses CT scans to form a 3-dimensional (3D) picture of the prostate before treatment. A computer uses this information about the size, shape, and location of the prostate cancer to determine how much radiation is needed to destroy it. With IMRT, high doses of radiation can be directed at the prostate without increasing the risk of damaging nearby organs.

Proton therapy. 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, protons can destroy cancer cells. Current research has not shown that proton therapy provides any more benefit to men with prostate cancer than traditional radiation therapy. 

Brachytherapy. Brachytherapy, or internal radiation therapy, is the insertion of radioactive sources directly into the prostate. These sources, called seeds, give off radiation just around the area in which they are inserted and may be used for hours (high-dose rate) or for weeks (low-dose rate). Low-dose rate seeds are left in the prostate permanently, even after all the radioactive material has been used up. For a man with a high-risk cancer, brachytherapy is usually combined with other treatments.

Radium-223. Radium-223 dichloride (Xofigo) is a radioactive substance. It is naturally attracted to areas of high bone turnover, which are areas where bone is being destroyed and replaced more than normal. Radium-223 delivers radiation directly to tumors found in the bone, limiting damage to healthy tissue. 

Radiation therapy may cause immediate side effects such as diarrhea or other problems with bowel function, such as gas, bleeding, and loss of control of bowel movements; increased urinary urge or frequency; fatigue; impotence; and rectal discomfort, burning, or pain. Most of these side effects usually go away after treatment, but impotence is usually permanent. Many side effects of radiation therapy may not show up until months or years after treatment.

Systemic Treatments

Doctors use treatments such as androgen deprivation therapy (ADT), chemotherapy, and novel agents to reach cancer cells throughout the body. This is called systemic treatment.

Androgen deprivation therapy (ADT)

Because prostate cancer growth is driven by male sex hormones called androgens, lowering levels of these hormones can help slow the growth of the cancer. The most common androgen is testosterone. Testosterone levels in the body can be lowered either by surgically removing the testicles, known as surgical castration, or by taking drugs that turn off the function of the testicles, called medical castration.

ADT is used to treat prostate cancer in different situations, including recurrent prostate cancer and metastatic prostate cancer. Metastatic prostate cancer is cancer that has spread throughout the body.

There is no role for ADT before surgery. Patients with intermediate-risk and high-risk prostate cancer undergoing definitive therapy with radiation are candidates for ADT. The timing, length, and duration of ADT is based on the patient’s risk (intermediate vs. high).

ADT can also be given after surgery for men found to have cancer in the lymph nodes (this happens during surgery) to eliminate any remaining cancer cells and reduce the chance the cancer will return. This is known as adjuvant therapy. Although these data are controversial, some specific patients appear to benefit from this approach.

ADT can help lengthen lives when used with radiation therapy for a prostate cancer that is more likely to recur. In some men with prostate cancer that has spread locally, called locally advanced or high-risk prostate cancer, ADT is given before, during, and after radiation therapy for 3 years. ADT should also be considered as adjuvant therapy if prostate cancer has been found in the lymph nodes after a radical prostatectomy. It may also be given for up to 3 years for men high-risk cancer and 6 months for men with intermediate-risk cancer.


Specific types of ADT

Bilateral orchiectomy. Bilateral orchiectomy is the surgical removal of both testicles and was the first treatment used for metastatic prostate more than 70 years ago. Even though this is an operation, it is considered an ADT because it removes the main source of testosterone production, the testicles. The effects of this surgery are permanent and cannot be reversed.

LHRH agonists. LHRH stands for luteinizing hormone-releasing hormone. Medications known as LHRH agonists prevent the testicles from receiving messages sent by the body to make testosterone. By blocking these signals, LHRH agonists reduce a man’s testosterone level just as well as removing his testicles. However, unlike surgical castration, the effects of LHRH agonists are reversible, so testosterone production usually begins again once a patient stops treatment.

LHRH agonists are injected or placed as small implants under the skin. Depending on the drug used, they may be given once a month or once a year. When LHRH agonists are first given, testosterone levels briefly increase before falling to very low levels. This effect, known as a “flare,” happens because of a temporary surge in testosterone production by the testicles in response to the way LHRH agonists work in the body. This flare may increase the activity of prostate cancer cells and cause symptoms and side effects, such as bone pain in men with cancer that has spread to the bone.

LHRH antagonist. This class of drugs, also called a gonadotropin-releasing hormone (GnRH) antagonist, stops the testicles from producing testosterone like LHRH agonists, but they reduce testosterone levels more quickly and do not cause a flare. The FDA has approved one drug, degarelix (Firmagon), given by monthly injection, to treat advanced prostate cancer. One side effect of this drug is that it may cause a severe allergic reaction.

Anti-androgens. While LHRH agonists and antagonists lower testosterone levels in the blood, anti-androgens block testosterone from binding to so-called “androgen receptors,” which are chemical structures in cancer cells that allow testosterone and other male hormones to enter the cells. These drugs, such as bicalutamide (Casodex), flutamide (Eulexin), and nilutamide (Nilandron), are taken as pills, usually by men who have “hormone sensitive” prostate cancer, which means that the prostate cancer still responds to ADT. Anti-androgens are not usually used by themselves in prostate cancer treatment.

Enzalutamide (Xtandi) is a newer type of anti-androgen that blocks signals from the androgen receptor that tell prostate cancer cells to grow and divide. Enzalutamide is approved by the FDA for men who have developed progressive metastatic prostate cancer despite testosterone suppression who have or have not previously received docetaxel-based chemotherapy.Treatment with enzalutamide has led to an improved overall survival in both patient populations.

Combined androgen blockade. Sometimes anti-androgens are combined with bilateral orchiectomy or LHRH agonist treatment to maximize the blockade of male hormones. This is because even after the testicles are no longer producing hormones, the adrenal glands still make small amounts of androgens. 

CYP17 inhibitors. Although the testicles are the main producers of testosterone, other cells in the body can still make small amounts of testosterone that may drive cancer growth. These include the adrenal gland and some prostate cancer cells themselves.

Abiraterone acetate (Zytiga) is a drug that blocks an enzyme called CYP17 and prevents these cells from making certain hormones, including adrenal androgens. Abiraterone acetate is in the form of a pill. Men take 4 pills per day along with prednisone (multiple brand names) twice a day. Abiraterone acetate has been approved by the FDA as a treatment for progressive metastatic castration-resistant prostate cancer with or without prior docetaxel-based chemotherapy. 

Abiraterone acetate may cause serious side effects such as high blood pressure, low blood potassium levels, and fluid retention. Other common side effects include weakness, joint swelling or pain, swelling in the legs or feet, hot flushes, diarrhea, vomiting, shortness of breath, and anemia.

Traditionally, ADT was given for the patient’s lifetime or until it stopped controlling the cancer. Then the cancer was called castration-resistant, meaning that ADT has stopped working, and other treatment options were considered. 

ADT will cause side effects that will generally go away after treatment has finished, except in men who have had an orchiectomy. General side effects of ADT include:

  • Impotence
  • Loss of sexual desire
  • Hot flashes with sweating
  • Gynecomastia, which is growth of breast tissue
  • Depression
  • Weight gain
  • Loss of muscle mass
  • Osteopenia or osteoporosis, which is thinning of bones


Although testosterone levels may recover after stopping ADT, some men who have had medical castration with LHRH agonists for many years may continue to have hormonal effects, even if they are no longer taking these drugs.

Another important side effect of ADT is the risk of developing metabolic syndrome. Metabolic syndrome is a set of conditions, such as obesity, high levels of blood cholesterol and high blood pressure that increases a person’s risk of heart disease, stroke, and diabetes. Currently, it is not certain how often this happens or exactly why it happens, but it is quite clear that patients who receive a surgical or medical castration with ADT have an increased risk of developing metabolic syndrome. The risk is increased even if the medical castration is temporary. 

 Aggressive management of side effects is imperative for patients receiving ADT. These include regular exercise, smoking cessation, healthy diet, vitamin D/calcium supplementation, and aggressive preventive cardiovascular follow-up care.

Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by stopping their ability to grow and divide. Chemotherapy is usually given by a medical oncologist, a doctor who specializes in treating cancer with medication.

Systemic chemotherapy gets into the bloodstream to reach cancer cells throughout the body. Chemotherapy for prostate cancer is given through an intravenous (IV) tube placed into a vein using a needle. It may help patients with advanced or castration-resistant prostate cancer. A chemotherapy regimen usually consists of a specific number of cycles given over a set period of time.        

There are several standard drugs used for prostate cancer. In general, standard chemotherapy begins with docetaxel combined with a steroid called prednisone. This chemotherapy has been shown to help men with advanced prostate cancer live longer compared with another chemotherapy drug, mitoxantrone (Novantrone). Mitoxantrone was one of the first chemotherapies approved for metastatic castration-resistant prostate cancer, but it is not commonly used. Mitoxantrone is most useful for controlling pain from the cancer and is sometimes considered in specific situations.


In general, the side effects of chemotherapy depend on the individual, the type of chemotherapy received, the dose used, and the length of treatment, but they can include fatigue, sores in the mouth and throat, diarrhea, 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 once treatment has finished. However, some side effects may continue, come back, or develop later. 


Vaccine Therapy

Sipuleucel-T (Provenge) is an immunotherapy. Immunotherapy is designed to boost the body’s natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function.

Sipuleucel-T is adapted for each patient. Before treatment, blood is removed from the patient in a process called leukapheresis. Special immune cells are separated from the patient’s blood, modified in the laboratory, and then put back into the patient. At this point, the patient’s immune system may recognize and destroy prostate cancer cells. It is difficult to know if this treatment is working to treat the cancer because it has not been shown to shrink the tumor, lower the PSA level, or keep the cancer from getting worse.