Prostate Cancer

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[restab title=”Objectives” active=”active”]

Objectives

The following module was designed to supplement medical students’ learning in the clinic. Please take the time to read through each module by clicking the headings below. Information on epidemiology, classification, signs & symptoms, diagnosis, pathology, staging, management, treatment and prognosis of prostate cancer is provided.

By the end of the tutorial, the following objectives should be addressed:
  1. Understand the incidence of prostate cancer in Canada.
  2. List some of the important risk factors for prostate cancer.
  3. Recognize the various screening tests that are used for prostate cancer.
  4. Understand the indications for prostate cancer screening.
  5. Know the benefits and risks of prostate cancer screening.
  6. Describe the basic anatomy and location of the prostate gland.
  7. Know the general prevalence of the different types of prostate cancer.
  8. Understand the classification of prostate adenocarcinoma.
  9. Recognize the signs & symptoms of prostate cancer and understand that localized prostate cancer is usually asymptomatic.
  10. Describe an approach to diagnose prostate cancer.
  11. Understand the Gleason score.
  12. List the patterns of prostate cancer spread.
  13. Understand the purpose of prostate cancer staging.
  14. Understand the tests used in prostate cancer staging.
  15. Know how the TNM stages apply to prostate cancer and be able to describe the prostate risk groupings (low, intermediate and high).
  16. Describe the factors influencing prostate cancer management.
  17. Recognize the different health care providers involved in prostate cancer management.
  18. Understand the different modalities used for prostate cancer treatment.
  19. Understand which treatment options are available for low, intermediate and high risk prostate cancer.
  20. Know some of the major benefits and risks for each treatment.
  21. Know the difference between watchful waiting and active surveillance.
  22. Understand PSA relapse.

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[restab title=”Anatomy Review”]

Anatomy Review

Source: Canadian Cancer Society

The prostate gland is a walnut sized exocrine gland that is part of the male reproductive system. It is located between the bladder & external urinary sphincter and the rectum, and below the pubis. It surrounds the prostatic urethra below the urinary bladder and is palpable on DRE. The cavernous nerves run posterior and laterally to the prostate gland from the pelvic plexus to the corpus cavernosum muscles. Prostate cancer and some treatments can damage these nerves affecting urinary, sexual and bowel functions.1

The prostate gland secretes an alkaline fluid that aids in sperm survival. PSA, prostatic acid phosphatase and other proteolytic enzymes are secreted by the prostate during ejaculation.Source: Canadian Cancer Society

The prostate gland is controlled by androgens, specifically, dihydrotestosterone.

The prostate can be divided into 4 zones for pathological classification. The majority of prostate cancers occur in the peripheral zone.

Table 1: Prostate Gland Zones
Zone Location Function Significance
Transitional Surrounds prostatic urethra 5% of glandular tissue BPH occurs here
20% of cancers occur here
Central Surrounds ejaculatory duct at the base of the gland 25% of glandular tissue 5% of cancers occur here – more likely to invade seminal vesicles
Peripheral Surrounds central zone
Palpable on DRE
70% of glandular tissue 75% of cancers occur here
Anterior Fibromuscular stroma Non-glandular tissue

[/restab]
[restab title=”Epidemiology”]

Epidemiology

Prostate cancer is now the most common cancer in Canadian men with 25,500 estimated new cases in 2009.1 In British Columbia, the incidence was rising at a rate of 3% per year through the 70’s to 90’s but levelled out in the mid 90’s.2 This increase may be due to detection from transurethral resection of the prostate (TURP) being performed more often for benign prostatic hyperplasia (BPH), prostate specific antigen (PSA) screening and DRE testing.There has been a slight reduction in prostate cancer mortality since the 90’s which has been attributed to treatment option availability.2

At the age of 50 years, men have a 40% chance of developing prostate cancer and by 80 years, 70% of men will have prostate cancer detectable on biopsy. Over 90% of those diagnosed with prostate cancer are over the age of 60. The median age of diagnosis is 72.

Risk Factors

Age:

The number one risk factor for prostate cancer is age. One in eight men between the ages of 60 and 80 will have prostate cancer and the risk continues to increase with age.

Genetics:

Approximately 10% of prostate cancer is attributed to genetic heritability. In those who are diagnosed before the age of 55, heritability plays a greater role. Having a first degree relative increases the relative risk by 1.5-2 fold and having 2 first degree relatives increases the risk 4-5 fold for prostate cancer.

Some genes that may be involved in prostate cancer development are c-myc (growth regulation), bcl-2 (anti-apoptosis), 5-alpha-reductase, and telomerase. Tumour suppressor genes such as p53, Rb, PTEN and TGF-β may also be involved.3

The BRCA-2 gene involved in breast and ovarian cancer also increases the risk of prostate cancer.3 A dominantly inherited gene, prostate cancer susceptibility gene (PRCA-1) has not been identified but may be involved in prostate cancer. 3

Ethnicity:

Prostate cancer is most prevalent in African American men which may be due to higher serum testosterone levels.4 There is an intermediate risk for prostate cancer in the Caucasian population in comparison. Asian Americans have a relative lower risk of developing prostate cancer.

There is a greater prevalence of prostate cancer in North America than in Asia, however, an increasing frequency of prostate cancer in Asian immigrants may suggest that the correlation is related to environmental, not genetic, causes.5

Testosterone:

A recent paper analysing studies correlating serum testosterone levels with prostate cancer risk have indicated there is no correlation between the two parameters.6

IGF-1:

Some studies have indicated that increased serum levels of IGF-1 may increase the risk of prostate cancer. IGF-1 may do this in three ways: acting as a mitotic agent on prostate cancer cells, decreasing SHBG, and increasing androgen synthesis. These studies are inconclusive and measuring IGF-1 levels in prostate cancer patients is not currently recommended.

Diet:

Diets high in saturated fat are associated with a 1.6-1.9 times greater risk of prostate cancer.3 This is more specifically associated with red meat and butter intake and other foods with high levels of alpha-linoleic acid. This fatty acid may cause an increase in androgen production.

The soybean isoflavinoid compound genistein may reduce the risk of prostate cancer by inhibiting the 5-alpha-reductase enzyme that converts testosterone to DHT.3 Vitamins A, E, and β-carotene may also be protective through anti-oxidation mechanisms but there is currently insufficient evidence to support this.6

A high body mass index (BMI) has also been correlated with increased prostate cancer recurrence and mortality.6

Summary:

Prostate cancer is the most common cancer in males in Canada. Some of the important risk factors for prostate cancer are: age, ethnicity, family history and diet. Smoking and alcohol are not associated with an increased risk for prostate cancer.

References:

1) Canadian Cancer Society, Cancer Statistics 2009. Available at: http://www.cancer.ca/canada-wide/about%20cancer/cancer%20statistics/canadian%20cancer%20statistics.aspx?sc_lang=. Accessed June 4, 2009.

2) Prostate Cancer Management Guidelines. BC Cancer Agency. 2009. Available at: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Genitourinary/Prostate/default.htm. Accessed June 3, 2009.

3) Shah, A. Essentials of Clinical Oncology. Vancouver: Somerset Publishing; 2004.

4) Fauci, AS et al. Harrison’s Principles of Internal Medicine: 17th edition. McGraw-Hill Medical; 2008.

5) Roddam AW et al. Endogenous Sex Hormones and Prostate Cancer: A Collaborative Analysis of 18 Prospective Studies. JNCI [serial online]. 2008 100(3):170-183. Available at: http://jnci.oxfordjournals.org/cgi/content/abstract/100/3/170. Accessed June 4, 2009.

6) Kantarijian, HM. Wolff, AR. Koller, CA. MD Anderson Manual of Medical Oncology. McGraw-Hill Medical; 2006.[/restab]
[restab title=”Screening”]

Screening

Screening Methods

Screening for prostate cancer is generally done using the Prostate Specific Antigen (PSA) serum test which was introduced in 1994. PSA is a prohormone protease that is specific to the prostate gland and produced in prostate acinar glands. After entering the glandular lumen it is cleaved by an enzyme and then enters the blood stream where it has a half life of two days. Its function is to liquefy semen coagulum, aiding in fertility.

Serum PSA Values

The baseline serum PSA values can be increased or decreased in a variety of situations, as outlined below.

Table 1: Causes for Increase and Decrease in Serum PSA Values
Increased PSA Decreased PSA
Prostate Cancer Finasteride (5-alpha reductase inhibitor – results in a 50% decrease in PSA readings thus cut-off for TRUS biopsy is 2ng/ml)
Benign Prostatic Hypertrophy (BPH) Prostatectomy (should be 0)
Prostatitis (normalize in 1 month) Anti-androgen therapy
Ejaculation (normalize in 2 days)
Trauma
• Digital Rectal Examination (DRE)
• Transrectal ultrasound (TRUS)
• Biopsy (normalize 1-2 months)

Normal PSA ranges can be characterized by age:

Table 2: Normal Serum PSA Values by Age
Age Value (ng/ml)
<50 <2.5
50-60 <3.5
60-70 <4.5
70-80 <6.5

Further investigations are generally recommended when the PSA values are greater than >4ng/ml. A value of 4-10ng/ml has a positive predictive value (PPV) for cancer of 20%, whereas values >10ng/ml have a PPV of 45%.

Free PSA Ratio

Prostate cancer can cause disruption of the acinar gland basement membranes which causes more PSA to enter the bloodstream before it is cleaved in the glandular lumen to become free PSA (unbound state). When it enters the bloodstream uncleaved, it is bound to the protein carrier alpha-1-chymotrypsin. Thus, in prostate cancer the ratio of free to total PSA decreases (unbound PSA/total PSA). This can be quantified by a blood test.4

Table 3: Free Total PSA Correlated with Increased Cancer Risk
Percent of free total PSA Percent risk of cancer
<25% Increased risk
<15% 50%
<7% 90%
PSA Density (PSAD)

The PSA values can also be related to the size of the prostate which is approximated by transrectal ultrasound (TRUS). This may be done to correct for increased PSA values due to BPH. In general, there is a 10x greater increase in PSA levels per gram of tissue with cancer than with BPH. PSAD is a relatively new parameter and is currently being evaluated for its sensitivity and specificity.

Table 4: PSA Density and Increased Cancer Risk4
PSAD Density (ng/ml per cm3) Interpretation
<0.1 BPH
0.1-0.15 Suspicious
>0.15 Suggestive of cancer
PSA Velocity

The PSA velocity measures the increase in PSA values over time. It can be used to predict the need for screening, treatment response, and survival rates post-treatment. A PSA velocity of greater than 0.75ng/ml/year is suggestive of prostate cancer.4

Digital Rectal Examination (DRE)

Digital rectal examination is also used to detect prostate enlargement. Malignant prostate masses will often feel hard, nodular, and irregular. 95% of prostate cancers are located in the peripheral zone which is palpable by DRE. Up to 50% of nodules found on DRE are malignant.

Table 5: Differential Diagnoses for Prostate Mass Detectable by DRE
Prostate cancer
Medical error
Normal asymmetry
Benign prostatic hypertrophy
Prostatitis
Calcification
Infarction
Cyst
TURP/biopsy scar
Prostatitis

Indications for Screening

Screening has been shown to increase detection rate of early stage cancer, but there is insufficient evidence supporting reduced mortality from prostate cancer.2

The current recommendations for PSA screening as set out by the BC Cancer Agency are to offer annual DRE and PSA tests to men between the ages of 50-70 years. Patients should be made aware of the risks and benefits before deciding whether they want to partake in screening. Screening should be stopped when the patient’s life expectancy is less than 10 years. PSA should also be evaluated in men presenting with lower urinary tract complaints or with positive findings on DRE.2

Table 5: Benefits and Risks of PSA Screening
Benefits Risks
Simple, reproducible, objective 75% of those with high PSA values do not have prostate cancer (false positives)2
More sensitive & specific than DRE alone 20-25% with normal PSA values may have microscopic prostate cancer (false negatives)2
Early diagnosis and treatment may increase survival Side effects of treatment protocols may be unnecessary if cancer does not affect life expectancy
Early diagnosis and treatment can prevent progression
Relatively low cost

Summary:

Prostate cancer is screened by the PSA test and DRE which should be offered to men 50-70 years old and in men with lower urinary tract symptoms. This test has not shown to decrease prostate cancer mortality and false positives and negatives are common. Other parameters such as PSA velocity, density, and free PSA may also aid in screening, diagnosis, and treatment follow-up.

References:

1) Canadian Cancer Society, Cancer Statistics 2009. Available at: http://www.cancer.ca/canada-wide/about%20cancer/cancer%20statistics/canadian%20cancer%20statistics.aspx?sc_lang=. Accessed June 4, 2009.

2) Prostate Cancer Management Guidelines. BC Cancer Agency. 2009. Available at: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Genitourinary/Prostate/default.htm. Accessed June 3, 2009.

3) Shah, A. Essentials of Clinical Oncology. Vancouver: Somerset Publishing; 2004.

4) Fauci, AS et al. Harrison’s Principles of Internal Medicine: 17th edition. McGraw-Hill Medical; 2008.

5) Roddam AW et al. Endogenous Sex Hormones and Prostate Cancer: A Collaborative Analysis of 18 Prospective Studies. JNCI [serial online]. 2008 100(3):170-183. Available at: http://jnci.oxfordjournals.org/cgi/content/abstract/100/3/170. Accessed June 4, 2009.

6) Kantarijian, HM. Wolff, AR. Koller, CA. MD Anderson Manual of Medical Oncology. McGraw-Hill Medical; 2006.[/restab]
[restab title=”Classification”]

Classification

Table 1: Prostate Cancer Subtypes
Cell type Classification Significance
Epithelial Adenocarcinoma Most common form of prostate cancer
Ductal adenocarcinoma Aggressive
Invades bladder neck
Treated with radical cystoprostatectomy
Most patients die within 4 years
Small cell carcinoma High rates of metastasis
Treated with combination therapy
Transitional cell carcinoma Primary or secondary from bladder direct invasion
Treated using bladder carcinoma protocols
Sarcomatoid carcinoma High grade
Endometrioid/large duct carcinoma More aggressive than adenocarcinoma
Similar treatment protocol
Non-epithelial Leiomyosarcoma Extremely rare
Very aggressive
Fibrosarcoma Extremely rare
Very aggressive
Rhabdosarcoma More common in children
May originate in the bladder
Primary lymphoma Extremely rare
Most commonly high grade

Prostate Adenocarcinoma

For treatment and classification purposes, adenocarcinoma is divided into 3 subcategories: low risk, intermediate risk, and high risk by the Canadian Consensus Guidelines as outlined below.

Table 2: Canadian Consensus Guidelines Classification of Prostate Cancers 2
Risk Group Stage Gleason Score PSA (ng/mL) 5 yr Biochemical evidence of no disease (bNED)
Low – must have all of: T2a <7 <10 80-90%
Intermediate – any of: Both sides
T2c (new staging)
7 10-20 70%
High – any of: T3+ 8-10 20+ 50%

Summary:

The prostate gland is a tubuloalveolar exocrine gland which is part of the male reproductive system. Prostate adenocarcinoma is the most common type of prostate cancer but other more aggressive forms exist. Prostate cancer is classified as low risk, intermediate risk and high risk according to Canadian Consensus Guidelines.

References:

1) DeVita VT, Hellman S, Rosenberg SA. Cancer: Principles & Practice of Oncology 7th Edition Vol 1. Lippincott Williams & Wilkins, Philadelphia; 2005.

2) Himu L, et al. Controversies in prostate cancer radiotherapy: consensus development. Can Jour Urol [serial online] 2001;8:1314-1322. Available at: http://www.canjurol.com/abstract.php?ArticleID=1021&version=1.0. Accessed July 23, 2009.[/restab]
[restab title=”Signs & Symptoms”]

Signs & Symptoms

Common Presenting Symptoms

Prostate cancer is most commonly detected by finding nodules or indurations on DRE or by PSA screening. This is because most prostate cancer patients are asymptomatic in early stage disease. However, some patients may present with urinary tract obstruction, bleeding or bone pain and these symptoms warrant further investigation.

Urinary Tract Obstruction

Voiding symptoms can occour in locally advanced prostate cancer when the prostatic urethra is obstructed; however, these symptoms are more likely to be due to benign prostatic hyperplasia (BPH). Urinary tract obstruction can present as urinary hesitancy, straining, dribbling, decreased or narrow stream, and incomplete bladder emptying. It is important to note BPH and prostate cancer have different etiologies and BPH is not a pre-cancerous lesion.1

The International Prostate Symptom Score (IPSS) is a questionnaire that is often used for assessment of voiding symptoms. The patients can fill out the survey themselves and a score out of 35 is calculated to assess voiding symptom severity and frequency. A copy of the questionnaire can be found here at the Urology Sciences Research Foundation.

Bleeding

Hematospermia, hematuria, and hematochezia may occur with prostate cancer. It is important to rule out other more common causes of these symptoms (e.g. hematuria caused by renal calculi, bladder tumours, etc).

Symptoms of Advanced Prostate Cancer

Bone Pain

Metastatic prostate cancer can spread to the bones and cause bone pain, most commonly in the lumbar spine, pelvis and femur. Bone metastasis can also cause pathological fractures in late stages.

Neurological Dysfunction

Prostate cancer can rarely present with urinary retention due to epidural metastases causing spinal cord compression. Prostate cancer may also lead to sexual dysfunction and changes in ejaculation.

Summary:

Prostate cancer can present with urinary obstructive symptoms but most commonly it is asymptomatic in early stages. Prostate cancer may cause a variety of symptoms due to local invasion or metastasis in later stages of the disease.

References:

1) DeVita VT, Hellman S, Rosenberg SA. Cancer: Principles & Practice of Oncology 7th Edition Vol 1. Lippincott Williams & Wilkins, Philadelphia; 2005.[/restab]
[restab title=”Diagnosis”]

Diagnosis

History

Information about past investigations such as PSA, DRE, and biopsy should be elicited. Questions about urinary obstructive symptoms, sexual dysfunction, genitourinary bleeding and bone pain should also be asked. A family history of prostate cancer should also be investigated.

Physical Exam

A digital rectal examination should be performed to assess for nodules, enlargement, or indurations of the peripheral zone of the prostate. Inguinal nodes and external genitalia should be examined for signs of locally advanced disease.

Examination of the skeleton and abdomen should also be completed to assess for signs of distant metastasis.

Laboratory Testing

The following laboratory tests may be completed as part of the complete prostate cancer workup if there are indications in the history of more advanced disease.

Table 1: Laboratory Investigations for Prostate Cancer Workup
Test parameter Significance
CBC Anemia, pancytopenia due to bone marrow involvement or chronic disease
PSA Elevated levels may indicate prostate cancer (see screening section)
Alkaline phosphatase, Ca2+ Bone metastasis
Electrolytes, Ur, Cr Kidney function, bladder obstruction
LFTs, Albumin Ability to treat with anti-androgen medication

Biopsy

Needle biopsy is the gold standard in prostate cancer diagnosis. The indications for prostate biopsy include: PSA >4ng/ml or above age-specific ranges, nodules, symmetry or indurations found on DRE, or evaluation of a T1a or greater tumour detected on TUPR. A transrectal ultrasound (TRUS) is used to guide biopsies and assess the prostate size. On ultrasound, cancer often appears hyperechoic (higher amplitude and density of echoes on ultrasound) with poorly defined margins while benign lesions appear hypoechoic (lower amplitude and density of echoes on ultrasound) with well-defined margins. However, these findings are not specific for prostate cancer and biopsy is required. Biopsy cores are taken from the visualized lesions and eight quadrants including the left & right apex, middle, and the base of peripheral zone.1

An 8 core biopsy has 90-95% sensitivity and a 10 core biopsy has 99% sensitivity. Sensitivity also depends on the prostate size, a 40cc gland needs 12 cores for 98% sensitivity while a 60cc gland needs 17 cores to achieve the same sensitivity. The false positive rate is 0-2%.

The biopsy provides information on location, size, and number of positive cores. The histological type can be assessed and a Gleason grade can be calculated (see pathology section for more information). Vascular, lymphatic, and neuron invasion may also be assessed as well as invasion beyond the prostate capsule.

Imaging

Figure 1: Bone Scan Showing Distant Metastases

Imaging is used to assess for local invasion and distant metastasis. Indications for a bone scan include symptomatic bone pain or a PSA greater than 15ng/ml. The incidence of bone metastasis is related to PSA levels. PSA levels of less than 8ng/ml rarely have skeletal involvement. False positives may occur with concurrent healing fractures, arthritis or Paget’s disease.2

CT scans and MRI of the abdomen and pelvis will be performed as indicated.

A relatively new technique, ProstaScint can be performed using SPECT imaging. An antibody to prostate specific membrane antigen (PSMA) can be used to detect the ratio of prostate antigen to muscle background (P/M) to assess pelvic node involvement for staging purposes. This is not commonly used in Canada.

Summary:

Diagnosis of prostate cancer involves history taking, physical examination, laboratory tests including PSA, TRUS core biopsy and imaging.

References:

1) DeVita VT, Hellman S, Rosenberg SA. Cancer: Principles & Practice of Oncology 7th Edition Vol 1. Lippincott Williams & Wilkins, Philadelphia; 2005.

2) Fauci, AS et al. Harrison’s Principles of Internal Medicine: 17th edition. McGraw-Hill Medical; 2008.[/restab]
[restab title=”Pathology”]

Pathology

Early signs of prostate gland atypia are called prostatic intraepithelial neoplasia (PIN). PIN is a precursor for prostate cancer consisting of atypical and dysplastic cells that are present within normal glands.1 Also, the basal cell layer may be lost and there may be signs of anaplasia.1 These lesions are often located adjacent to areas of proliferative inflammatory atrophy, or (PIA) which consists of undifferentiated prostate epithelial cells.1 PIN appears as early as ten years before prostate cancer, but not all lesions become cancerous.

PIN is graded based on the amount of atypia. Grades I & II are not readily associated with cancer. Grade III PIN is an indication for additional biopsies to search for cancer in other areas of the prostate. Studies are in progress to determine if finasteride, a 5-α-reductase inhibitor, can be used in patients with PIN to prevent progression to adenocarcinoma.

On gross examination, prostate cancer appears heterogeneous, pale yellow with grey flecks and multifocal.

Prostate cancer histopathology is evaluated using the Gleason Scoring System. Each biopsy core is graded from 1-5. The two most common patterns, the primary (most common) and secondary (second most common) grades, are added to give a Gleason score out of 10. If only one pattern is present, it is doubled to give the Gleason score. Higher scores indicate more aggressive cancers and worse prognosis. 85% of cancers are Gleason Grades 5-7.1 Transitional zone cancers are usually higher grade and extend outside the prostate.1

Primary Grade (/5) + Secondary Grade (/5) = Gleason Score (/10)

It is important to note that a Gleason Score of a 7 with a Grade 4 primary and Grade 3 secondary (4+3) pattern has a worse prognosis than the same score with a Grade 3 primary and Grade 4 secondary (3+4) pattern.2

Table 1: Gleason Grading System
Grade Appearance
1 Normal prostate – uniform glands, little stroma
2 Well formed glands, enlarged with more stroma
3 Variable sized glands mixed with normal stroma
or “cribriform” pattern of smooth cell nests without stroma
4 Incomplete gland formation – fusion, cell nests, cell cords, cribriform patterns
5 Grossly abnormal, no gland formations or lumens
Table 2: Gleason Score and Risk Classification
Score Risk
2-6 Low risk
7 Intermediate risk
8-10 High risk

Pattern of Spread

Local

Prostate cancer is often multifocal with numerous heterogeneous tumours. Local spread is common via areas of thin and weak capsule to the bladder neck, seminal vesicles, ejaculatory duct insertion, and rarely to the bladder. Apex tumours spread earlier in their course as there are more capsule defects at this location.1

Systemic

Prostate cancer can spread systemically to the obturator, hypogastric, presacral and external iliac lymph nodes.1

Hematogenous

The most common location for distant metastases is the bone. Very rarely, the liver and lungs are involved.1

Summary:

To assess prostate cancer pathology the Gleason score is calculated based on microscopic examination of biopsy cores and assesses degree of glandular atypia. Prostate cancer can spread locally, hematogenously, and via the lymphatic system.

References:

1) DeVita VT, Hellman S, Rosenberg SA. Cancer: Principles & Practice of Oncology 7th Edition Vol 1. Lippincott Williams & Wilkins, Philadelphia; 2005.

2) Tanago EA, McAcinch JW. Smith’s General Urology 17th edition. McGraw-Hill Medical; 2008.[/restab]
[restab title=”Staging”]

Staging

Prostate cancer staging involves classifying the extent and progression of the disease using the TNM system. Staging helps in deciding a patient’s treatment plan, understanding prognosis and allowing research comparison. Staging also allows different health care professionals to communicate and provides international standardization.

History, physical examination, laboratory tests including PSA and TRUS biopsy are used in prostate cancer staging. If radical prostatectomy and lymphadenectomy are performed, this will also provide valuable information. Chest X-ray, CT, MRI and bone scans may also be used to evaluate metastasis.

Initial Evaluation

The DRE and PSA can give an initial indication of the prostate gland size, degree of enlargement and location but neither test is sensitive and specific and further testing must be done. TRUS can indicate which areas of the prostate are hypoechoic, which is a decreased tissue density detected by ultrasound waves. This finding is non-specific and biopsy is needed for diagnosis.

Tissue Pathology

Prostate gland biopsy provides information on the cancer type, degree of atypia, presence of PIN, Gleason score, and rectal, fibrous/adipose tissue, and seminal vesicle involvement.1

If radical prostatectomy is indicated for treatment, it provides information on the type, size, percent involvement, Gleason score, extra-prostatic involvement, positive margins, vascular invasion and lymph node involvement.Both biopsy and radical prostatectomy can provide important information for staging and prognosis. Specifically, positive margins and extra-prostatic involvement can predict the success of different treatment options.

Lymph Node Assessment

In recent years, pelvic lymph node involvement on initial presentation has decreased and not all patients will undergo lymph node dissection.1 Calculations based on TNM, PSA levels and Gleason scores can provide an estimated risk of metastasis. If the risk is low, lymph node dissection may not be performed. Dissection is now performed by laparoscopic pelvic lymphadenectomy.

Bone Metastasis

A bone scan, or bone scintography, is performed if the patient is symptomatic, has a PSA greater than 10ng/ml, stage T3/4 or a Gleason score of greater than 8 to assess for bone involvement. This is the most common location for prostate cancer metastasis.

Imaging

MRI and CT scanning are not as useful in staging prostate cancer as they are in other cancers. Research has shown no statistical difference between TRUS and MRI for prostate cancer staging.1 CT has not been shown to provide more information than DRE as it cannot accurately detect extra-prostatic involvement or differentiate between benign and malignant lesions.1

CT is useful, however, to look for intrabdominal lymph node metastases. A CT scan should be strongly considered in patients with high risk disease (see risk groupings).

The greatest challenge in prostate cancer staging is identifying patients with microscopic extra-prostate invasion that may not be apparent on biopsy. Research is currently being conducted to find techniques that can be used to assess for this in the initial work up.1

Tumor Node Metastasis (TNM) System

Prostate cancer is staged worldwide using the TNM system which was updated in 2002.

T – Tumour extent
N – Nodal involvement
M – Metastasis

Table 1: TNM Classification of Prostate Cancer1
TNM Description 10 year survival2
TX Cannot assess primary tumour
T0 No evidence of primary tumour
T1a Cancer in <5% of tissue resected via TUPR
Non-palpable by DRE, not visible by imaging
95%
T1b Cancer in >5% of tissue resected via TUPR
Non-palpable by DRE, not visible by imaging
T1c Cancer confirmed by needle biopsy performed due to increased PSA
Non-palpable by DRE, not visible by imaging
T2a Cancer in <50% of one lobe, confined to the prostate 80%
T2b Cancer in >50% of one lobe, confined to the prostate
T2c Cancer in both lobes, confined to the prostate
T3a Cancer extends unilaterally outside capsule
T3b Cancer extends bilaterally outside capsule
T3c Cancer extends into seminal vesicles
T4a Fixed tumour or invasion into bladder neck, external sphincter, rectum
T4b Tumour invades levator muscles or rectum
NX Cannot assess lymph nodes
N0 No cancer in regional nodes
N1 Cancer metastasis in regional nodes 40%
MX Cannot assess metastases
M1a Non-regional lymph node metastasis 10%
M1b Bone metastasis
M1c Other site metastasis

Stages

The TMN classification can be grouped into Stages from I through to IV. While the Stages are important, it is the classification of low, intermediate and high risk that is used to make most treatment decisions.

Table 2: Stages I-IV Classification of Prostate Cancer Based on TNM Grouping1
Stage Tumour Nodes Metastasis
I 1a 0 0
II 1a 0 0
II 1b 0 0
II 1c 0 0
II 2 0 0
III 3 0 0
IV 4 0 0
IV Any 1 0
IV Any Any 1
Table 2: Canadian Consensus Guidelines Classification of Prostate Cancer3
Risk Group Stage Gleason Score PSA (ng/mL) 5 yr Biochemical evidence of no disease (bNED)
Low – must have all of these: T2a <7 <10 80-90%
Intermediate – any of: Both sides
T2c (new staging)
7 10-20 70%
High – any of: T3+ 8-10 20+ 50%

Summary:

Prostate cancer staging involves assessment of the extent and the progression of prostate cancer. This is done using laboratory testing, biopsy, imaging, and/or surgery. The tests involved in staging depend on the extent of the disease and the risk of metastasis. The TNM system is used for staging and can help guide treatment protocols along with the low, intermediate and high risk classification system.

References:

1) Kirby RS, Christmas TJ, Brawer MK. Prostate Cancer: Second Edition. Mosby, London; 2001.

2) So, A. The A, B, C’s of Prostate Cancer. Lecture Notes [MEDICOL Web site]. Accessed June 10th, 2009. Available at: http://www.med.ubc.ca/medicol/.

3) Himu, L et al. Controversies in prostate cancer radiotherapy: consensus development. Can Jour Urol [serial online].:2001,8:1314-1322. Available at: http://www.canjurol.com/abstract.php?ArticleID=1021&version=1.0. Accessed July 23, 2009.[/restab]
[restab title=”Treatment”]

Treatment

The treatment for prostate cancer can be divided into three categories, low risk, intermediate, and high risk. This classification, along with the TNM staging and patient performance status, provides guidance for physicians and patients in selecting treatment options.  The advantages and disadvantages of treatment options are discussed with the patient and appropriate referrals are made. Active surveillance, watchful waiting, curative, or palliative treatment options may be explored.

Treatment: Low Risk Prostate Cancer
Treatment: Intermediate Risk Prostate Cancer
Treatment: High Risk Prostate Cancer
Treatment: Metastatic Prostate Cancer

[/restab]
[restab title=”Prognosis”]

Prognosis

The prognosis of prostate cancer can be evaluated by the Gleason score, PSA levels, and the clinical stage. Molecular factors such as gene mutations also affect prognosis.

A PSA relapse after treatment is defined differently depending on the treatment modality. After prostatectomy, a PSA value above 0.3ng/ml on two consecutive blood tests may be defined as a relapse.

After radiation therapy, an increase in PSA value after reaching the lowest level (which may take 1-2 years) may be considered as a PSA relapse. The Phoenix definition for PSA biochemical relapse is the nadir PSA value plus 2 ng/ml which can predict overall survival from prostate cancer.1

Biochemical evidence of no disease (BNED) depends on spread beyond the capsule, positive margins, seminal vesicle involvement, and nodal disease. PSA biochemical failures are 2-3 times more common than clinical failures which are defined by signs and symptoms of recurrent cancer. Local failures are greater if there are positive margins after surgery. Redevelopment of nodules on DRE may also indicate relapsing and will require additional treatment.

Summary:

Prostate cancer biochemical relapse can be assessed by monitoring PSA levels. The definition of PSA relapse varies depending on the treatment modality. Biochemical relapse does not necessarily indicate clinical relapse, characterized by signs and symptoms of recurrent cancer.

References:

1) Abramowitz MC et al. The Phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer: Cancer [serial online].:2007,112;55-60. Available at: http://www3.interscience.wiley.com/journal/116836291/abstract?CRETRY=1&SRETRY=0. Accessed July 13, 2009.[/restab]
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Virtual Patient Case

This case study was designed to supplement your knowledge on the workup of prostate cancer and test what you have learned after going through module. Use your mouse to click through the slides and answer each question in the text box provided.

Note: This case can be completed on an Ipad. To do this download the (free) Articulate Mobile Player for the Ipad by clicking here.

Click here to start the Prostate Cancer Virtual Patient Case[/restab]
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Evaluation

Thank you for using Learn Oncology. This website was designed to supplement teaching in oncology. While the material is targeted to medical students it is our hope that a variety of health care professionals can use this site. Feedback on your experience will help us to improve the resources. Responses are anonymous. Thank you.

Click here to fill out the Prostate Cancer Module Survey[/restab]
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Major Contributors:

Allison Lee & Elana Thau – Medical Students
Dr. Paris Ann Ingledew – MD, FRCP Radiation Oncologist[/restab][/restabs]


Last Updated: August 2014