Prostate Cancer

Definition/Description

Prostate cancer affects the prostate gland, which is part of the reproductive system and functions to create seminal fluid[1]. Prostate cancer is the most common type of cancer in men after skin cancer, and is the second leading cancer related cause of death in men. It is slow growing and affects one third of all males by the age of 50.[2]  Prostate cancer commonly metastasizes, primarily spreading to bone, which frequently causes lumbar pain[2]. Even with such a fairly high mortality and metastasis rate, the microscopic changes that occur in the prostate can be slow growing and may never cause health issues and often cause no signs or symptoms[2]. Variations in the rate of prostate cancer progression and spreading suggests genetic involvement along with familial predisposition and diet[2]. Overall, prostate cancer has become a significant issue due to the fact that it has become so prevalent. Overall, more men are being diagnosed due to an increase in routine screenings, and more men are living longer with the disease due advancements in treatment.[2] 

Abnormal Prostate Gland
[3]

Prevalence

The American Cancer Society estimates that in 2016 the United States will have about 180,890 new cases of prostate cancer, and around 26,120 deaths due to the same disease. Approximately 1 in every 7 men will be diagnosed with prostate cancer[4]. Prostate cancer is more common in African-American males compared to white or Hispanic males, and is least common in Asians and Native American men[2]. It most commonly affects men over the age of 50 with an increasing incidence with age, and about 6 out of every 10 cases diagnosed are of men age 65 or older. It is rare in men under 45 years of age[2].

Death due to prostate cancer is currently about 1 in every 39 men. Even though the lifetime prevalence of being diagnosed with prostate cancer is high, most men will not die due to this disease process[4]

Characteristics/Clinical Presentation

Clinical Signs and Symptoms[2][5]
Diagram demonstrating how prostate cancer can cause urinary issues
 [3]
  • Urinary retention or other urinary complaints                           
  • Low back pain, inner thigh or perineal pain or stiffness
  • Hematuria
  • Blood in semen 
  • Suprapubic or pelvic pain/discomfort
  • Sexual dysfunction

Early prostate cancer may be asymptomatic. Routine screenings of prostate cancer are commonly being done on asymptomatic men. The listed signs and symptoms may also be present with other prostate related disease processes such as Benign Prostatic Hyperplasia (BPH) or Prostatitis.[5]

Manifestations of Metastasized Prostate Cancer[2][5]:

  • Sciatica
  • Bone pain and lower extremity pain
  • Lymphedema of groin or lower extremities 
  • Neurological changes from spinal cord compression
  • Anemia
  • Weight loss and loss of appetite


Associated signs and symptoms to ask the patient about include:

  • Melena
  • Sudden moderate to high fever
  • Chills
  • Changes in bowel or bladder function

Associated Co-morbidities

A retrospective study by Chamie et al. titled “Comorbidities, Treatment and Ensuing Survival in Men with Prostate Cancer” looked at men diagnosed with prostate cancer and how comorbidities affected their mortality and treatment.[6]

Survival differences corresponding to 5-year and 10-year survival rates were studied. “The respective 5-year and 10-year survival for those without any comorbid conditions were 88% and 75%; men with moderate-severe COPD were 50% and 12%; diabetes with end-organ damage were 57% and 36%.” So, just based off of this single study conducted it can be speculated that comorbidities such as, COPD and diabetes could factor into the mortality of those diagnosed with prostate cancer.[6]

Also, some studies have shown that there is a lower risk of getting a less dangerous form of prostate cancer and an increased risk of getting a more advanced form of it in obese men. Some studies have also found that obesity may create a greater risk of dying from prostate cancer.[4] 

Medications

There are many medications that can be used in the treatment of prostate cancer. Pharmacotherapy is used in the treatment of prostate cancer in hopes to induce remission, reduce morbidity and reduce complications.[5] A list of FDA approved drugs for the treatment of prostate cancer can be found at the National Cancer Institute: http://www.cancer.gov/about-cancer/treatment/drugs/prostate.

Some of the more common medications used for prostate cancer include[5]:

  • Hormone Therapy: used to stop the production of testosterone or to block uptake of testosterone by cancer cells[7]
Gonadotropin-releasing hormone (GnRH) agonists: causes medical castration which reduces production of testosterone
  1. Leurpolide
  2. Triptorelin
  3. Goserelin
  4. Histrelin

Androgen antagonists: inhibits interaction with testosterone

  1. Abiraterone
  2. Bicalutamide
  3. Degarelix
  4. Flutamide
  5. Nilutamide
  6. Enzalutamide
  • Bisphophonates: used in men with castrate-resistant cancer and with bone metastases 
  1. Zoledronic acid
  • Antifungal agents: works similar to antiandrogens and are used when antiandrogens fail
  1. Ketoconazole
  • Chemotherapeutic agents
  • Corticosteroids: modifies the body's immune response
  1. Prednisone
  2. Hydrocortisone
  3. Dexamethasone
  • Immunologic agents: stimulates patient's own immune system
  1. Provenge


Diagnostic Tests/Lab Tests/Lab Values

Screening:

Prostate-specific antigen (PSA) test:

  • A blood test used to test for elevated levels of PSA, which occurs with any changes in the prostate.
  • The risk of disease increases as the PSA level increases; however, a normal level of PDA has not been determined[2].
  • If prostate cancer develops the PSA levels will typically increase past 4 ng/mL of blood, according to the American Cancer Society.

             -PSA level between 4 and 10: 25% chance of having prostate cancer

             -PSA greater than 10: over 50% chance of having prostate cancer

  • No PSA level guarantees the absence of prostate cancer[5].

             -Approximately 15% of men with a PSA below 4 will be positive for prostate cancer when biopsied3

  • There are several factors that may increase PSA levels[4]

The U.S. Preventive Services Task Force[8] recommends against PSA-based screening for prostate cancer due to the test often producing false positives, which can then lead to harmful side effects from proceeding diagnostic tests or treatment[5]. This recommendation is considered controversial and is currently in the process of being updated according to the U.S. Preventive Services Task Force website.[8]


Digital rectal examination (DRE):

  • A DRE is an exam in which the doctor inserts a finger into the rectum to allow the ability to palpate the back of the prostate gland, which allows for the ability to feel possible cancers or bumps[4]
  • Majority of patients diagnosed with prostate cancer have abnormal PSA levels, but normal DRE results[5]
  • This test may still be included in screening because even though it is less effective than a PSA blood test overall it may still be able to detect cancer in men that may demonstrate normal PSA levels


Prostate cancer often grows slowly; therefore, men without symptoms of prostate cancer who do not have a 10-year life expectancy may not be screened. Overall health status, not just age, is important when making decisions, and patients should talk to their healthcare provider about the pros and cons of being tested and treated for prostate cancer. [4][9]

Recommended age to start screening for prostate cancer according to the American Cancer Society[4]:
• 50 years of age for men with an average risk, and who have at least a 10-year life expectancy
• 40-45 years of age for African American men and those with a first-degree relative diagnosed with prostate cancer before 65 years old
• 40 years of age for men with several first-degree relatives who had prostate cancer at an early age


Diagnosis:

Biopsy: 
Demonstration of a prostate biopsy
  • The diagnosis of prostate cancer is established via a biopsy of the prostate gland, and may be indicated for individuals who have elevated PSA levels.[5]
  • A small piece of the prostate gland is removed and examined under a microscope for cancer cells. If cancer cells are found then a Gleason score will be determined from the biopsy.
  • A Gleason score indicates how likely the cancer is to spread. It ranges from 2–10, the lower the score the less likely it is that the cancer will spread[9]
  • False-negative results often occur; therefore, multiple biopsies may be done before prostate cancer can be detected and confirmed[5]


Transrectal Ultrasound (TRUS)[4][9]:

  • A small probe is inserted into the rectum and uses sound waves (ultrasound) to create a picture of the prostate.
  • TRUS is not utilized as a screening tool because it cannot always differentiate between normal tissue and cancerous tissue. Instead, it is often used in conjunction when a prostate biopsy to help guide the biopsy needles into the right area of the prostate.
  • TRUS can also be utilized to determine the PSA density and to tell which treatment choices are appropriate.[4]


Staging[2]:

Stage I: Cancer cannot be felt during a DRE, but it may be found during surgery being done for another reason. The cancer has not yet spread to other areas.

Stage II: Cancer can be felt during a DRE or discovered during a biopsy. The cancer has not yet spread.

Stage III: The cancer has spread to nearby tissue 

Stage IV: The cancer has spread to lymph nodes or to other parts of the body 

Stages of Prostate Cancer
[10]

Etiology/Causes

The cause of prostate cancer is not yet known; however, there are several known risk factors that have been shown to indicate an increase in the risk of developing this type of cancer.[4]

Non Modifiable Risk Factors:

  • Advancing Age

     -Most men who acquire prostate cancer are 65 years or older
     -It is very rare to develop prostate cancer before 45 years of age

  • Race/Ethnicity

     -African-American men have an increased risk of developing prostate cancer compared to white or Hispanic men, and the risk is less in men of Asian and Native American descent.[2]
     -The mortality rates in African-American men are more than twice as high as in any other racial group.[5]

  • Geography

     -Prostate cancer occurs more frequently in North America, northwestern Europe, Australia, and on the Caribbean islands, and it is less common in Asia, Africa, Central America, and South America.[4]

  • Family History

     -There is an increased risk of developing prostate cancer if a brother or father had the disease, and the risk increases the more first degree relatives that have been affected.[2]

  • Gene Mutations[4]
  • Viruses
  • Hormones

     -A study performed showed a possible correlation between elevated levels of luteinizing hormone and of                                                      testosterone:dihydrotestosterone and a mild increase in risk of prostate cancer[5]

Modifiable Risk Factors[2][4]:

  • Diet

     -A diet high in animal fat, red meat, and high-fat dairy products may be attributed to an increase risk in developing prostate cancer.

  • Occupational exposures

     -Such as chemicals (herbicides, pesticides, and toxic combustible products), cadmium, and other metals

  • Multiple sex partners
  • Low levels of vitamins or selenium

Systemic Involvement

Early prostate cancer is often asymptomatic and is often diagnosed because men seek medical attention for issues regarding urinary dysfunction (i.e. retention) or low back, hip, or leg pain. Prostate cancer almost exclusively metastasizes to bone of the pelvis, spine, or femur via the bloodstream or lymphatic system and spreads in the early stages. It has also been known to spread to the bladder, rectum, and distant organs such as the liver, lung, and brain via the lymphatics.[2]  

Medical Management (current best evidence)

Localized prostate cancer[4][5][9]
Typical treatments for clinically localized prostate cancer can include these following treatment options:

  • Prostatectomy: This involves the removal of the prostate gland. A radical prostatectomy is the removal of the prostate gland and some surrounding tissue.
    Radical Prostatectomy
    [11]
  • Radiation therapy: Use of high-energy radiation to try to kill the cancer cells.

            1. External beam radiation therapy: the radiation is directed into the cancer cells from the outside of the body
            2. Brachytherapy (Internal radiation therapy): Radioactive pellets surgically implanted into the cancerous area to try to kill the                             cells from the inside of the body

  • Active surveillance: Monitoring the cancer by regularly performing PSA tests and DRE tests, and taking action only if the cancer or symptoms increase
  • Hormone therapy: Aims to block the cancer cells from obtaining the essential hormones needed to grow
  • Cryotherapy: Treatment includes placing a probe near the cancer cells to try to kill them by freezing them
  • Chemotherapy: Use of drugs (oral or intravenous) to try to kill or reduce in size the cancer cells
  • Vaccine treatment: Cancer vaccine made specifically for each man that works to boost the body’s immune system to kill prostate cancer cells. This is mainly used for advanced cancers that are not responding to hormone therapy.


Metastatic prostate cancer[4]
Rarely can prostate cancer that has metastasized be cured. Management of these patients usually include such treatments as:

  • Preventing and treating cancer spread to bones via medications (i.e. Biphosphonates, Denosumab, etc.)
  • Relief of particular symptoms (i.e. relieving bone pain via pain medication)
  • Trying to slow further progression of disease

Physical Therapy Management (current best evidence)

In a retrospective study by Alappattu et al. titled "Clinical Characteristics of Patients With Cancer Referred for Outpatient Physical Therapy" outlined common impairments seen post cancer treatment and how physical therapy can help treat these impairments.[12]


There were 418 patients examined in this study, 169 (40.4%) of which were referred for having genitourinary cancer. 80% of the patients in the genitourinary classification had a diagnosis of prostate cancer. Some of the common impairments found with all cancer types after examination included cancer-related fatigue, deconditioning, pain, muscle shortening, contractures, peripheral neuropathy, lymphedema and genitourinary dysfunction.[12]


The most common neuromusculoskeletal impairments found with genitourinary cancer included[12]:

  • Strength (88.2%)
  • Incontinence (81.7%)
  • Urgency (75.8%)
  • Soft tissue (59.5%)
  • Pain (25.5%)

Incontinence is one of the most common side effects of prostate cancer treatment.[12]

  • Pelvic-floor rehabilitation and behavioral modifications have proven effective in the recovery of incontinence postprostatectomy.
  • Parekh et al. evaluated continence outcomes in patients who received 3 pre-prostatectomy pelvic-floor muscle training sessions and 3 post-operative pelvic-floor muscle training sessions.[12]
  • At 12 weeks, when compared to the control group who did not receive pelvic-floor muscle training, the treatment group had significantly faster return to continence.

Physical therapists working with individuals post-prostate cancer treatment or individuals with a history of prostate cancer should always screen for genitourinary dysfunction as incontinence may remain for a period of time after cancer treatment. The physical therapist should treat or refer appropriately.[12]

Targeted aerobic training and strengthening exercises for prevention and management of cancer related fatigue exhibits efficacy when used during and after treatment in various types of cancer according to some studies.[12]

Although incontinence is the most common impairment associated with prostate cancer treatment, the patient should be treated as a whole and all impairments should be addressed.

Differential Diagnosis[2][5]

  • Obstruction of lower urinary tract
  • Prostatitis
  • Acute Bacterial Prostatitis and Prostatic abscess
  • Bacterial prostatitis
  • Benign Prostatic Hyperplasia
  • Tuberculosis of Genitourinary System
  • Musculoskeletal: Low back, hip, or leg pain

Although bony metastases of prostate cancer are often blastic as found by radiologic imaging, they can cause lytic lesions which may mimic Paget's disease. Some bony metastases may cause a pathologic fracture which is a common symptom of Paget's disease. In men being treated with luteinizing hormone-releasing hormone (LHRH), osteoporotic fractures must be differentiated from pathologic fractures.[5]

Any sudden neurologic changes of the lower extremities such has weakness in older men with a history of prostate cancer should raise awareness of possible spinal cord compression and should be sent for emergency treatment. Brain metatsases with associted neurological symptoms are rare, but should be considered when screening older men with a history of prostate cancer.[5]

Pelvic masses and bone lesions are presentations of lymphoma and are very rare when in association with prostate cancer. Cases of lymphomas with prostate cancer have been reported and should be taken into consideration while screening.[5]

Case Reports/ Case Studies

1. Glode, LM. Case Reports on Prostate Cancer. Reviews in Urology 2004;6(Suppl 7):S39-S45. Published 2004. Available from: PMC.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1472886/

2. Kubicka-Wolkowska J, Debska-Szmich S, Lisik-Habib M, Noweta M, Potemski P. Malignan acanthosis nigricans associated with prostate cancer: a case report. BMC Urology. 2014;14:88. Published November 2014. Available from: PMC.

http://www.ncbi.nlm.nih.gov/pubmed/25399333

3. Bourlon M, Glode L, Crawford E. Base of the Skull Metastases in Metastatic Castration-Resistant Prostate Cancer. Oncology Journal. December 2014. Available from: Cancer network.

http://www.cancernetwork.com/oncology-journal/base-skull-metastases-metastatic-castration-resistant-prostate-cancer

4. Aksoy S, Orhan K, Kursun S, Eray Kolsuz M, Celikten B. Metastasis of prostate carcinoma in the mandible manifesting as numb chin syndrome. World Journal of Surgical Oncology. 2014;12:401. Published December 2014. Available from: PMC.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326431/ 

Resources[4]

American Cancer Society
Toll-free number: 1-800-227-2345
Website: www.cancer.org

Prostate Cancer Foundation (formerly CaPCURE)
Toll-free number: 1-800-757-2873 (1-800-757-CURE) or 1-310-570-4700
Website: www.pcf.org

US Too International, Inc.
Toll-free number: 1-800-808-7866 (1-800-80-US-TOO)
Website: www.ustoo.com

Urology Care Foundation
Toll-free number: 1-800-828-7866
Website: www.urologyhealth.org

National Association for Continence
Toll-free number: 1-800-252-3337 (1-800-BLADDER)
Website: www.nafc.org

National Cancer Institute
Toll-free number: 1-800-422-6237 (1-800-4-CANCER); TYY: 1-800-332-8615
Website: www.cancer.gov

National Coalition for Cancer Survivorship
Toll-free number: 1-888-650-9127
Website: www.canceradvocacy.org

To get more information, visit the National Cancer Institute’s (NCI’s) Prostate Cancer Treatment Option Overview, which a site that can help to find a healthcare provider or treatment site that cares for cancer. Also, go to Facing Forward: Life After Cancer Treatment for more information about treatment and can help help assist with various treatment sources.[4]

Recent Related Research (from Pubmed)

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References

  1. WebMD. What Is the Prostate? http://www.webmd.com/men/what-is-the-prostate (accessed 9 April 2016).
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 Goodman C, Synder T. Differential Diagnosis for Physical Therapists Screening for Referral. St. Louis, Missouri: Elsevier Saunders 2013.
  3. 3.0 3.1 Wikipedia. Prostate Cancer. https://en.m.wikipedia.org/wiki/Prostate_cancer# (accessed 10 April 2016).
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 American Cancer Society. Prostate Cancer. http://www.cancer.org/cancer/prostatecancer/index (accessed 9 April 2016).
  5. 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 5.15 5.16 Medscape. Prostate Cancer. http://emedicine.medscape.com/article/1967731-overview (accessed 9 April 2016)
  6. 6.0 6.1 Chamie K, Daskivich TJ, Kwan L, Labo J, Dash A, Greenfield S, Litwin MS. Comorbidities, treatment and ensuing survival in men with prostate cancer. Journal of General Internal Medicine 2012 May;27(5):492-9. http://www.ncbi.nlm.nih.gov/pubmed/21935751 (accessed 9 April 2016).
  7. Mayo Clinic. Diseases and Conditions Prostate Cancer. http://www.mayoclinic.org/diseases-conditions/prostate-cancer/multimedia/prostate-cancer/img-20006744 (accessed 9 April 2016)
  8. 8.0 8.1 U.S. Preventive Services Task Force. Prostate Cancer: Screening. http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/prostate-cancer-screening?ds=1&s=prostate%20cancer (accessed 9 April 2016).
  9. 9.0 9.1 9.2 9.3 Centers for Disease Control and Prevention. Prostate Cancer. http://www.cdc.gov/cancer/prostate/index.htm (accessed 9 April 2016).
  10. Wikipedia. Cancer staging. https://en.wikipedia.org/wiki/Cancer_staging (accessed 10 April 2016).
  11. Wikipedia. Prostatectomy. https://en.wikipedia.org/wiki/Prostatectomy (accessed 10 April 2016).
  12. 12.0 12.1 12.2 12.3 12.4 12.5 12.6 Alappattu MJ, Coronado RA, Lee D, Bour B, George SZ. Clinical characteristics of patients with cancer referred for outpatient physical therapy. Physical Therapy 2015 April;95(4):526-38. http://ptjournal.apta.org/content/95/4/526.long (accessed 10 April 2016).