All About Prostate Cancer

OncoLink Team
Última Vez Revisión: 28 de febrero de 2019

What is the prostate?

The prostate is a small gland that only men have. Normally, the prostate is about the size of a walnut. The prostate is located underneath the bladder and in front of the rectum. The prostate makes and stores fluid that is part of semen. This fluid is released from a man's penis during ejaculation. The prostate is signaled to do its job by the male hormone testosterone, which influences the behavior of the prostate gland and prostate cancer. Nerves to the penis, which are important in producing and maintaining an erection, run very close to the prostate. The prostate completely encircles the tube that carries urine from the bladder to the penis, called the urethra. If the prostate enlarges, it can block the flow of urine from the bladder, making it difficult for a man to urinate.

What is prostate cancer?

Prostate cancer occurs when cells in the prostate begin to grow out of control. Sometimes these cells escape out of the prostate, invade nearby tissues or spread throughout the body. Typically, prostate cancer is a slow-growing cancer. Most prostate cancers are adenocarcinomas. There are some rare types of prostate cancer including sarcomas, neuroendocrine tumors, transitional cell carcinomas or small cell carcinomas. The type of prostate cancer impacts the treatments used to treat the disease.

Sometimes prostate cancer will grow quickly and spread to nearby lymph nodes. Lymph nodes are small, pea-sized pieces of tissue that filter and clean lymph, a clear liquid waste product. If prostate cancer has spread to your lymph nodes when it is diagnosed, it means that there is a higher chance that it has spread to other areas of the body as well. If and when prostate cancer cells gain access to the bloodstream, they can deposit in various bones throughout the body, at which point the prostate cancer is said to have metastasized to the bones. 

What causes prostate cancer and am I at risk?

Every man is at risk for prostate cancer as he ages. Although prostate cancer can strike younger men, about 6 out of 10 cases are diagnosed in men over the age of 65 with the average age of diagnosis being 66. After non-melanoma skin cancer, prostate is the most common cancer diagnosed in men in the United States. The American Cancer Society estimates there will be 174,650 new cases of prostate cancer annually.

Although there are several known risk factors for getting prostate cancer, no one knows exactly why one man gets it and another doesn't. Some important risk factors for prostate cancer are: 

  • Age: The incidence of prostate cancer rises quickly after the age of 60, and the majority of men will have some form of prostate cancer after the age of 80. One of the sayings about prostate cancer is that men over the age of 80 are more likely to die with prostate cancer than from prostate cancer. This saying means that many older men have low-volume, slower-growing prostate cancer that is not going to affect life expectancy because the cancer will take a very long time to grow and become clinically important. However, this saying is only a generalization; sometimes prostate cancer can grow quickly, even in older men.
  • Ethnicity: Prostate cancer is more common in African-American men and Caribbean men of African ancestry. African-American men have a 1.6-fold higher chance of being diagnosed with prostate cancer than Caucasian and Latino men. Asian and Native American men have the lowest chances of getting prostate cancer. The reason for these ethnic differences in prostate cancer risk is not known.
  • Genetics: A family history of prostate cancer increases a man's chances of developing the disease, particularly in men with a father or brother have had prostate cancer. There are also inherited genetic mutations that may increase the risk of prostate cancer. These include BRCA1 and BRCA2 gene mutations and HPNCC (Lynch syndrome). A mutation in the HOXB13 gene may be linked to familial early age prostate cancer. Finally, RNASEL is a gene which suppresses tumor growth. A mutation in this gene may influence the development of prostate cancer cells. 
  • Diet: There is some evidence that a man's diet may affect his risk of developing prostate cancer. A high fat diet, particularly a diet high in animal fats, may increase prostate cancer risk.  A few studies have suggested that a diet low in vegetables causes an increased risk of prostate cancer. In some studies, a diet high in tomatoes (lycopene) or a diet high in omega-3-fatty acids has been shown to decrease prostate cancer risk. 

How can I prevent prostate cancer?

The best way to try and prevent prostate cancer is to modify the risk factors for prostate cancer that you have control over. Eat a low-fat diet that is rich in fruits and vegetables and low in animal fats. It is always a good idea to maintain a healthy weight, get plenty of exercise and not to smoke or to quit smoking.

What screening tests are used for prostate cancer?

There are two tests used for prostate cancer screening, the digital rectal exam (DRE) and a blood tests called the prostate specific antigen (PSA).

The DRE is performed in your provider's office. Because the prostate is so close to the rectum, your provider can feel it by inserting a gloved, lubricated finger into your anus. Your provider can feel if there are lumps, asymmetries, or if your prostate is enlarged. A digital rectal exam is uncomfortable, but not painful. It is a useful test, but it is not perfect. Some small cancers can be missed as only the bottom and sides of the prostate can be examined in this manner. Although it isn't a full proof test, it becomes more useful when it is combined with another test called a PSA.

The PSA (prostate specific antigen) test is a blood test that looks for this specific protein that is only made in the body by the prostate gland. Normal prostate tissue makes some of this antigen, but prostate cancer usually makes much more, and keeps making it, causing PSA levels to keep rising. By checking to see if your PSA is elevated, your provider can screen you for prostate cancer. The PSA test isn't perfect either, because some tumors won't elevate the PSA, while some other processes (like benign prostatic hyperplasia/BPH and prostatitis) can cause it to be falsely elevated. However, the higher your PSA is, the more likely the elevation is to be caused by a prostate cancer. The cut-off that your provider typically uses is 4.0 ng/ml, meaning that anything below 4.0 ng/ml is considered likely normal and anything above it is abnormal and may warrant a prostate biopsy. If your PSA is elevated, or you have an abnormal digital rectal exam, then you need to get further evaluation; however, this doesn't necessarily mean that you have prostate cancer. The only way to know for sure whether or not you have cancer is to get a sample of your prostate via biopsy.

The American Cancer Society (ACS) recommends that men make an informed decision on whether or not they should be screened after discussing the risks and benefits of screening with their healthcare provider. Screening is not recommended in men without symptoms of prostate cancer if they have a life expectancy of less than ten years. Men at average risk of developing prostate cancer should begin this conversation at age 50. African American men and men with one relative with prostate cancer should talk with their healthcare provider about screening beginning at age 45. Men at the highest risk, those with more than one first degree relative with prostate cancer at an early age should begin talking about screening at age 40. Repeat screening is based on baseline PSA results, but typically occurs every 1-2 years.

What are the signs of prostate cancer?

Most early prostate cancers are detected with PSA tests or digital rectal exams before they cause any symptoms. However, more advanced prostate cancers can cause a variety of symptoms including: 

  • Trouble starting to urinate. 
  • Urinating much more frequently than usual. 
  • The feeling that you can't release all of your urine. 
  • Pain with urination or ejaculation. 
  • Blood in your urine or semen. 
  • Impotence/erectile dysfunction.
  • Bone pain. 
  • Numbness in the lower extremities.  
  • Loss of bladder or bowel control.

All of these symptoms can be caused by a variety of things besides prostate cancer, so experiencing them doesn't necessarily mean you have prostate cancer. When older men have problems urinating, it is usually caused by a problem called benign prostatic hyperplasia (BPH), which is not prostate cancer. If you experience any of these symptoms, you need to see your provider for evaluation. 

How is prostate cancer diagnosed?

If you have symptoms suspicious for a prostate cancer, your provider will perform a digital rectal exam and a PSA blood test. If either of those two tests are abnormal, then most likely your provider will recommend that you have a prostate biopsy. A biopsy is the only way to know for sure if you have cancer, as it allows your providers to get cells that can be examined under a microscope. 

The most common way that a biopsy is done is with a trans-rectal ultrasound (TRUS). A trans-rectal ultrasound is a thin cylinder that emits sound waves and monitors them when they bounce off of tissue. It is inserted into your rectum, and allows the doctor performing the biopsy to view your prostate and choose where to remove the tissue for further evaluation. Any suspicious areas are biopsied. In addition, some tissue will be removed from all of the different parts of the prostate (to make sure they don't miss any cancers that may be small and growing in one particular area). The procedure is done while you are awake, with the help of some numbing medicine. Unfortunately, a trans-rectal ultrasound isn't a perfect tool. Even though many samples are taken, it can occasionally miss the area of the cancer. If this happens, and your PSA remains elevated, you may need to have the procedure repeated.

Once the tissue is removed, a provider called a pathologist will examine the specimen under a microscope. The pathologist can tell if it is cancer or not; and, if it is cancerous the pathologist will characterize it by what type of prostate cancer it is and how abnormal it looks (known as the grade). The pathologist then characterizes how much the cancer looks like normal prostate tissue. This is known as the grade of the tumor. Pathologists often use a scale, called the Gleason score, when they grade prostate tumors. The Gleason score can range from 2 to 10, with 2 meaning the tumor cells look more like normal prostate tissue and 10 the tumor cells look most abnormal compared to normal prostate cells. Generally, the more abnormal the tumor looks, the more aggressive it is. Sometimes there are two scores, as two areas of tumor in the prostate are assessed. This score, combined with your PSA and the stage of the tumor will result in your prostate cancer being assigned a risk group. This risk group designation helps to define your treatment options. This system is included in the staging appendix at the end of this article.

Your provider may order other tests including a bone scan, CT scan or MRI to see if the cancer has spread to the bones, lymph nodes or other organs. 

How is prostate cancer staged?

With these tests, a stage is assigned to help decide the treatment plan. The stage of cancer, or extent of disease, is based on information gathered through the various tests done as the diagnosis and work-up of the cancer is being performed. 

Prostate cancer is most commonly staged using the “TNM system.” The TNM system is used to describe many types of cancers. In prostate cancer it has four components: T-describing the extent of the "primary" tumor (describes the tumor itself), N-describing if there is cancer in the lymph nodes; M-describing the spread to other organs (metastases) and G which describes the Gleason score and takes into account the PSA and the histologic grade of the tumor.

The staging system is very complex. The entire staging system is outlined at the end of this article. Though complicated, the staging system helps healthcare providers determine the extent of the cancer, and in turn, make treatment decisions for a patient's cancer. 

What are the treatments for prostate cancer?

There are many different ways to treat prostate cancer, and you will most likely be consulting multiple types of healthcare providers before making a final decision. For prostate cancer, it is important that you get a second opinion. You should talk to both urologists and radiation oncologists to hear about the benefits and risks of surgery, hormonal therapy and radiation in your particular case. If your prostate cancer has already spread at the time of diagnosis, you will also need a medical oncologist to talk about chemotherapy. The most important thing is to review your options and make a decision that best suits your lifestyle, beliefs and values.

Active Surveillance (Watchful Waiting)

Some patients choose to receive no therapy for their prostate cancer in the hopes that it will grow very slowly. By avoiding any therapy, they avoid the side effects that come along with surgery, radiation, or hormones. Active surveillance is appropriate for older men with small, low-grade tumors, slowly rising PSAs, and multiple other medical problems. Active surveillance can be considered in patients who have a life expectancy of less than 10 years as long as the cancer isn't large or of a high grade. Men who choose to undergo watchful waiting should have a PSA every 6 months, a DRE every 12 months and need to have a repeat biopsy every 12 months. However, it is never really clear what change in clinical status should start active treatment. Also, if the tumor has progressed, they may no longer be eligible for curative therapy.

Surgery

Surgery is a common form of treatment for men with prostate cancer. Surgery attempts to cure prostate cancer by removing the entire prostate and getting all of the cancer out of the body. An attempt at a surgical cure for prostate cancer is usually done with early stage prostate cancers. However, sometimes surgery will be used to relieve symptoms in advanced stage prostate cancers. Surgery for prostate cancer is generally felt to be equivalent to radiation for prostate cancer in terms of survival, especially in early stage, low to intermediate grade cancers. The decision to have surgery versus radiation is often made on the basis of the patient's age and health status. The two different approaches have different side effect profiles depending on the patient's age.

The most common surgical procedure for prostate cancer is a radical prostatectomy. Radical prostatectomy means that the entire prostate gland is removed from around the tube that connects the bladder to the penis (the urethra). This surgery can be done in two different ways, the retropubic approach and the perineal approach. The retropubic approach means that incision in made in the lower abdomen, while the perineal approach means that the incision is made between the scrotum and the anus. Often times during a retropubic approach, the surgeon will remove some lymph nodes in the area and have them quickly examined by a pathologist for signs of cancer. If the nodes have cancer, then the surgeon will not proceed with the operation. This is the major reason a retropubic approach is used in most surgeries today.

Radical prostatectomies are very safe surgeries with few life threatening complications; however, there is a significant risk for other side effects. Both urinary incontinence (not being able to hold in your urine) and impotence (inability to achieve and maintain an erection) are commonly associated with this procedure. Sometimes, particularly with lower grade and smaller cancers, a nerve sparing prostatectomy can be performed. This type of prostatectomy can decrease the chance that you will be impotent after the procedure. However, there is always a risk and not every patient is a candidate for a nerve sparing prostatectomy. The risk for impotency and incontinence increases with age; this is why younger men are often recommended to have surgery while older men are recommended to have radiation. The skill of your particular surgeon also influences your chances of having these side effects during a radical prostatectomy.

Another surgical approach, which is being used more and more commonly, is the robot-assisted radical prostatectomy (RAP). As with non-robotic prostatectomy techniques, the entire prostate is removed. To perform the procedure, several tiny incisions are made in the patient's abdomen and long, thin laparoscopic instruments are inserted and attached to the robot. The robot moves the instruments according to the instruction of the urologist who is seated at the robotic console. Therefore, the surgeon is controlling the movement of the robot the whole time. The rationale for this approach is that the slender arms of the robot can reach places and turn at angles that a surgeon’s hand cannot. RAP has some advantages over traditional prostatectomy techniques, which include decreased blood loss and shorter hospitalization and recovery. However, it is costlier, and also carries the risks of impotence and incontinence. Research studies have found that cancer cure rates with RAP are equivalent to traditional radical prostatectomy. Of course, as with all surgical techniques, success will depend in part on the skill and experience of the surgeon.

Talk to your surgeon about their complication rates before your operation. With surgery, urinary incontinence and impotence are often most severe right after the operation and generally get better with time. There are things that your providers can recommend to help you with either of these problems. Talk to your urologist about your options.

Radiation

Prostate cancer is commonly treated with radiation therapy. Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. Radiation is used in various stages of prostate cancer. Radiation helps avoid surgery in patients who are too ill to risk having anesthesia. Radiation is usually offered to older patients in the case of early stage prostate cancer because its side effect profile may be more favorable than surgery in the elderly. Radiation can have impotence rates similar to surgery, but the risk of urinary incontinence is very low. Impotence develops months to years after the radiation treatment, unlike with surgery, which tends to have the side effects occur immediately. Other side effects from radiation include bladder irritation, which can cause urinary frequency and urgency as well as bladder pain, and diarrhea or rectal bleeding. Your radiation oncologist tries to limit the amount of radiation to other organs, but often the bladder and rectum can get some radiation exposure because they are in such close proximity to the prostate.

Radiation therapy for prostate cancer either comes from an external source (external beam radiation) or an internal source where small radioactive seeds are implanted into the patient's prostate (brachytherapy). (Which type is right for me?) External beam radiation therapy requires patients to come in 5 days a week for 6-9 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. Brachytherapy is done as a one-time insertion, in the operating room. Brachytherapy cannot be done in all patients and is usually reserved for early stage prostate cancers. Your radiation oncologist can answer questions about the utility, process, and side effects of both of these types of radiation therapy in your particular case.

Another form of external beam radiation therapy for prostate cancer uses protons rather than x-rays to kill tumor cells. Protons are the positively charged components within the nucleus of an atom. They are used to deliver radiation because they deposit most of their cell-killing energy within the tumor site (in this case, the prostate gland), thus delivering less dose to the tissues where the proton beams entered, and virtually no dose beyond the area being treated (so-called "exit dose"). Because of the potential to decrease dose deposition within normal tissues, many researchers are interested in learning whether treatment with protons has fewer and/or less severe long-term side effects compared to standard x-ray radiation treatments. Protons may have a theoretical advantage, but so far there is little evidence to "prove" that they superior. 

Hormonal Deprivation Therapy

Both normal prostate tissue and prostate cancers depend on male sex hormones, called androgens, to grow and replicate. Testosterone is an androgen that is very important to the prostate gland. Men make androgens in their testicles. One of the ways to treat prostate cancer is to remove androgens from the body, thus making the cancer shrink and then grow more slowly. This is called androgen deprivation therapy (ADT). There are a few different ways to remove androgens: 

  • Orciectomy: removal of a man's testicles. 
  • Medications:
    • LHRH agonists: block the production of androgens.
    • Anti-androgens: block androgen receptors.
    • Estrogen/DES.

The choice of which ADT to use is based on the extent of disease, and concurrent (with radiation) or neo-adjuvant (before radiation) treatment being given. Sometimes, a combination of methods of decreasing androgens are often used in the same patient. Using LHRH agonists with anti-androgens can achieve what is known as a total androgen blockade. Another use for hormones is in patients who present with metastatic disease. After a while, all prostate cancers will become resistant to hormonal therapy. However, this often takes many years. Hormonal therapy can increase survival time in patients with extensive disease or patients who choose not to undergo surgery or radiation.

There are a number of side effects associated with hormonal therapy. Hormonal therapy will almost universally cause impotence and the loss of your sex drive. It can also cause breast enlargement, hot flashes, and muscle and bone loss (osteoporosis). There are some things your providers can prescribe to help with bone loss and hot flashes, but little can be done about loss of libido and impotence.

Chemotherapy

Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. Chemotherapy for prostate cancer is generally only reserved for very advanced cancers that are no longer responsive to hormonal therapy. There are a number of chemotherapy drugs that can be used for prostate cancer, and they are often used in combinations. Common medications used in the treatment of prostate cancer include docetaxel and cabazitaxel in combination with corticosteroids (prednisone). Metastatic prostate cancer may be treated with additional therapies including abiraterone, enzalutamide and mitoxantrone.

Immunotherapy uses the body’s immune system to fight cancer. Two immunotherapy medications, sipuleucel-T and pembrolizumab may be used in the treatment of some patients with prostate cancer. Sipuleucel-T (Provenge) was approved in 2010 as a treatment of metastatic prostate cancer when the cancer no longer responds to hormonal treatments. It is a form of immunotherapy that involves harvesting a specific type of the patient’s own white blood cells and combining the cells with a protein called prostatic acid phosphatase (PAP) found on prostate cancer cells, in order to activate the white blood cells. The cells are then given back to the patient about 3 days later, in a process similar to a blood transfusion. Pembrolizumab is indicated in prostate cancers that have a microsatellite instability-high(MSH)/mismatched repair deficient(dMMR). Your provider will test your tumor for this abnormality.

If prostate cancer cells spread they often metastasize to the bone and treatment is necessary. Two medications are recommended for the treatment of bone metastasis in prostate cancer are zoledronic acid and denosumab.

Clinical Trials 

There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

Follow-up Care and Survivorship

Once you have been treated for prostate cancer, you should be closely followed for a recurrence. At first, you will have follow-up visits fairly often. The longer you are free of disease, the less often you will have to go for checkups. Your provider will tell you when they want follow-up visits, PSAs, and x-rays or scans, depending on your case. Your provider will also probably do digital rectal exams regularly during your office visits. It is very important that you let your provider know about any symptoms you are experiencing, and that you keep all of your follow-up appointments. 

Fear of recurrence, relationship challenges, financial impact of cancer treatment, employment issues and coping strategies are common emotional and practical issues experienced by prostate cancer survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer. 

Cancer survivorship is a relatively new focus of oncology care. With some 15 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan on OncoLink

Resources for More Information 

Prostate Cancer Foundation 

Leading philanthropic organization funding and accelerating prostate cancer research globally. Also provides information about prostate cancer, treatment and resources to help patients and families. 

http://www.pcf.org/ 

Us Too 

Offers peer-to-peer support and educational materials to help men and their families/caregivers make informed decisions about prostate cancer detection, treatment options and related side effects. 

http://www.ustoo.org/Home 

MaleCare 

Provides cancer support for men with anal, prostate and breast cancer, with emphasis on African-American and gay males. Provides multiple language support. 

http://malecare.org/ 

His Prostate Cancer 

A support network for women whose husband or partner has prostate cancer. 

http://www.hisprostatecancer.com/ 

Prostate Health Education Network 

A support and education resource for African American men with prostate cancer. 

http://www.prostatehealthed.org/ 

Appendix: AJCC Complete Staging for Prostate Cancer (8th ed., 2017)

Primary Tumor-Clinical (cT)

Description

TX

Primary tumor cannot be assessed

T0

No evidence of primary tumor

T1 

Clinically inapparent tumor that is not palpable

T1a

Tumor incidental histologic finding in 5% or less of tissue resected

T1b

Tumor incidental histologic finding in more that 5% of tissue resected

T1c

Tumor identified by needle biopsy found in one or both sides, but not palpable

T2

Tumor is palpable and confined within prostate

T2a

Tumor involved one-half of one side or less

T2b

Tumor involved more than one-half of one side or less

T2c

Tumor involved both sides

T3

Extraprostatic tumor that is not fixed or does not invade adjacent structure

T3a

Extraprostatic tumor that is not fixed or does not invade adjacent structures

T3b

Tumor invades seminal vesicle(s)

T4

Tumor is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall

 

Pathological Tumor (pT)

Description

T2

Organ confined

T3

Extraprostatic extension

T3a

Extraprostatic extension (unilateral or bilateral) or microscopic invasion of the bladder neck

T3b

Tumor invades seminal vesicle(s)

T4

Tumor is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall

 

Regional Lymph Nodes(N)

Description

NX

Regional lymph nodes cannot be assessed

N0

No positive regional nodes

N1 

Metastases in regional node(s)

 

Distant Metastasis(M)

Description

M0

No distant metastasis

M1

Distant metastasis

M1a

Non-regional lymph node(s)

M1b

Bone(s)

M1c

Other site(s) with or without bone disease

 

Histologic Grade Group 

Gleason Score

Gleason Pattern

1

≤6

≤3+3

2

7

3+4

3

7

4+3

4

8

4+4, 3+5, 5+3

5

9 or 10

4+5, 5+4, 5+5

 

Stage Grouping

T

N

M

PSA

Grade Group

Stage I

cT1a-c

cT2a

pT2

N0

N0

N0

M0

M0

M0

PSA <10

PSA <10

PSA <10

1

1

1

Stage IIA

cT1a-c

cT2a

pT2

CT2b

cT2c

N0

N0

N0

N0

N0

M0

M0

M0

M0

M0

PSA ≥10<20

PSA ≥10<20

PSA ≥10<20

PSA<20

PSA<20

1

1

1

1

1

Stage IIB

T1-2

N0

M0

PSA<20

2

Stage IIC

T1-2

T1-2

N0

N0

M0

M0

PSA<20

PSA<20

3

4

Stage IIIA

T1-2

N0

M0

PSA≤20

1-4

Stage IIIB

T3-4

N0

M0

Any PSA

1-4

Stage IIIC

Any T

N0

M0

Any PSA

5

Stage IVA

Any T

N1

M0

Any PSA

Any

Stage IVB

Any T 

Any N

M1

Any PSA

Any

Referencias

The American Cancer Society. (2018). Prostate Cancer. Retrieved from https://www.cancer.org/cancer/prostate-cancer.html, 27 Feb 2019.

Chang, S. L., Kibel, A. S., Brooks, J. D., & Chung, B. I. (2015). The impact of robotic surgery on the surgical management of prostate cancer in the USA. BJU international115(6), 929-936.

Chen, R. C., Basak, R., Meyer, A. M., Kuo, T. M., Carpenter, W. R., Agans, R. P., ... & Spearman, K. C. (2017). Association between choice of radical prostatectomy, external beam radiotherapy, brachytherapy, or active surveillance and patient-reported quality of life among men with localized prostate cancer. Jama317(11), 1141-1150.

Donovan, J. L., Hamdy, F. C., Lane, J. A., Mason, M., Metcalfe, C., Walsh, E., ... & Lennon, T. (2016). Patient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer. New England Journal of Medicine375(15), 1425-1437.

Fizazi, K., Tran, N., Fein, L., Matsubara, N., Rodriguez-Antolin, A., Alekseev, B. Y., ... & De Porre, P. (2017). Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. New England Journal of Medicine377(4), 352-360.

Kantoff, P. W., Higano, C. S., Shore, N. D., Berger, E. R., Small, E. J., Penson, D. F., ... & Xu, Y. (2010). Sipuleucel-T immunotherapy for castration-resistant prostate cancer. New England Journal of Medicine363(5), 411-422.

National Comprehensive Cancer Network-NCCN.(2018). Prostate cancer clinical practice guidelines. Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf, 27 Feb 2019.

Pan, H. Y., Jiang, J., Hoffman, K. E., Tang, C., Choi, S. L., Nguyen, Q. N., ... & Smith, B. D. (2018). Comparative toxicities and cost of intensity-modulated radiotherapy, proton radiation, and stereotactic body radiotherapy among younger men with prostate Cancer. Journal of Clinical Oncology36(18), 1823-1830.

Sartor, O., & de Bono, J. S. (2018). Metastatic prostate cancer. New England Journal of Medicine378(7), 645-657.

Shipley, W. U., Seiferheld, W., Lukka, H. R., Major, P. P., Heney, N. M., Grignon, D. J., ... & Pisansky, T. M. (2017). Radiation with or without antiandrogen therapy in recurrent prostate cancer. New England Journal of Medicine376(5), 417-428.

Sweeney, C. J., Chen, Y. H., Carducci, M., Liu, G., Jarrard, D. F., Eisenberger, M., ... & Dreicer, R. (2015). Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. New England Journal of Medicine373(8), 737-746.

Tosoian, J. J., Mamawala, M., Epstein, J. I., Landis, P., Wolf, S., Trock, B. J., & Carter, H. B. (2015). Intermediate and longer-term outcomes from a prospective active-surveillance program for favorable-risk prostate cancer. Journal of Clinical Oncology33(30), 3379.

Wallis, C. J., Saskin, R., Choo, R., Herschorn, S., Kodama, R. T., Satkunasivam, R., ... & Nam, R. K. (2016). Surgery versus radiotherapy for clinically-localized prostate cancer: a systematic review and meta-analysis. European urology70(1), 21-30.

 

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