eMedicine Specialties > Radiology > Genitourinary

Prostate Carcinoma

Richard Clements, MBBCh, Consultant, Department of Clinical Radiology, Royal Gwent Hospital, South Wales
Contributor Information and Disclosures

Updated: Apr 18, 2007

Introduction

Background

Prostate cancer is an important growing health problem, presenting a challenge to urologists, radiologists, and oncologists. Prostate cancer is the most common nondermatologic cancer, yet despite this frequent occurrence, the clinical course is often unpredictable. Most prostate cancers are slow growing and do not manifest themselves during the man's lifetime; in fact, many men are found to have had incidental microscopic foci of prostate cancer at postmortem examination. Thus, many men die with prostate cancer rather than from prostate cancer; however, some prostate cancers are aggressive, with a rapidly worsening course.

At present, many men are identified as having early prostate cancer through the use of prostate-specific antigen (PSA) screening, but few indicators currently distinguish progressive prostate tumors from those that are more indolent.

The treatment of prostate cancer is controversial; different options range from early aggressive treatments, such as radical prostatectomy and radical radiotherapy, to deferred treatments (ie, treating men if and when the disease progresses and becomes symptomatic).

Pathophysiology

Approximately 95% of prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer occur in approximately 5% of patients; these include small cell carcinoma, mucinous carcinoma, endometrioid carcinoma (prostatic ductal carcinoma), transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma, and neuroendocrine carcinoma.

Prostate cancer is frequently multifocal within the prostate; 70% of prostate cancers occur in the peripheral zone (PZ), and approximately 20% are found in the transition zone (TZ). Some authors have claimed that TZ prostate cancers are relatively nonaggressive, whereas PZ cancers are more aggressive and tend to invade the periprostatic tissues.

Contemporary biopsy strategies concentrate on the PZ and largely ignore cancer in the TZ. A study of 148 patients with TZ cancers based on radical prostatectomy specimens revealed that 80% of TZ tumors were organ confined.¹ A secondary tumor was found in the PZ in 52% of cases. About 15% of the cases had capsular penetration; 2.7%, seminal vesicle invasion; and 3.4%, lymph node metastases.

Histopathologic diagnosis of prostate cancer

Disturbances of architecture, invasion, and anaplasia are the important histopathologic criteria for the diagnosis of prostate cancer. Dysplastic lesions of the prostate occur and are characterized by loss of cellular polarity, increase in nuclear size with hyperchromicity, and pleomorphism. Such dysplastic lesions are termed prostatic intraepithelial neoplasia (PIN). PIN is a histologic appearance that many pathologists consider to be a preinvasive stage of some prostate cancers and may be classified as low grade or high grade. In its most severe form, PIN is regarded as carcinoma in situ.

Grading

Various grading systems have been proposed, but the Gleason system is one of the most widely used internationally. It recognizes a primary and a secondary pattern, as well as 5 subpatterns in each. The sum of the 2 patterns is the Gleason score, which has prognostic significance. Patients with a Gleason score of 4 or less do well clinically, whereas patients with a score of 8-9 do poorly.

Staging

The prostate does not have a true capsule, but it does have an outer fibromuscular band called the capsule. Tumor spread outside the prostate may occur by means of capsular penetration, invasion of the seminal vesicles, or local extension along the neurovascular bundles. The usual sites of metastases from prostate cancer are the lymph nodes, bones, and lungs. Skeletal metastases are common in advanced prostate cancer, but hepatic metastases are uncommon.

The spread of prostate cancer to the lymph nodes involves the obturator nodes, then the common iliac and para-aortic lymph nodes. Pelvic lymph nodes are involved initially; the inguinal nodes are not involved. Metastatic spread to bone is common in patients with advanced prostate cancer; this typically occurs as osteoblastic sclerotic metastases. Occasionally, lytic metastases are seen.

The TNM (tumor, node, metastasis) staging system was revised in 1997 and is considered the international standard for prostate cancer staging and categorizes the prostate as follows²:

• Primary tumor (T)
  
  
  • TX - Primary tumor is not assessable
  • T0 - No evidence of primary tumor
  • T1 - Clinically inapparent tumor, not palpable or visible by imaging
    
    
    • T1a - Incidental histologic finding in 5% or less of the tumor resected (tissue is obtained during transurethral resection for symptoms of outflow tract obstruction)
    • T1b - Incidental histologic finding in more than 5% of the tissue resected (tissue is obtained during transurethral resection for symptoms of outflow tract obstruction)
    • T1c - Tumor identified by needle biopsy (performed because of elevated PSA levels)
  • T2 - Tumor confined within the prostate
    
    
    • T2a - Tumor involving 1 lobe
    • T2b - Tumor involving both lobes
  • T3 - Tumor extending through the prostatic capsule
    
    
    • T3a - Extracapsular extension (unilateral or bilateral)
    • T3b - Tumor invading the seminal vesicles
  • T4 - Tumor fixed or invading adjacent structures other than the seminal vesicles, bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall
• Regional lymph nodes (N)
  
  
  • NX - Regional lymph nodes not assessable
  • N0 - No regional lymph node metastasis
  • N1 - Regional lymph node metastasis
• Distant metastasis (M)
  
  
  • MX - Distant metastasis is not assessable
  • M0 - No distant metastasis
  • M1 - Distant metastasis
    
    
    • M1a - Nonregional lymph node metastasis
    • M1b - Bone metastasis
    • M1c - Metastasis at other sites

The most recent version of the TNM classification system is from 2002.²

Frequency

United States

Prostate cancer is the most common nondermatologic cancer and the second most common cause of cancer-related deaths in American men. The number of prostate cancers recorded in cancer registries in the United States and the United Kingdom has increased markedly in the past 15 years. This change predominantly represents an increase in the number of cancers diagnosed rather than a real increase in the number of cancers in the population. In 2006, 234,460 new cases and 27,350 deaths were estimated to occur. It was determined that approximately 91% of these new cases would be diagnosed at local or regional stages.³

International

Incidence and mortality rates vary widely throughout the world, with the highest reported incidence in black American men. South American countries, such as Brazil, and Scandinavian countries, such as Sweden and Norway, also have high reported incidences, whereas Asian countries, such as Japan and China, report low incidences. (See also the US data above.)

Mortality/Morbidity

In a man aged 50 years, risk analysis shows that the lifetime risk of microscopic prostate cancer is approximately 42%, the risk of clinical prostate cancer is 10%, and the risk of fatal prostate cancer is 3%.

• Mortality for prostate cancer has decreased in the United States since 1992, and it has decreased in the United Kingdom since 1995. The decrease in the United States is greater than that in the United Kingdom.
• Maximum mortality (ie, the greatest rate of mortality) is in those aged 85 years and older.

Race

• The incidence of prostate cancer is higher in blacks (100 cases per 100,000) than in whites (70 cases per 100,000).
• African Caribbean and African American men are at higher risk than men in other ethnic groups.
• The incidence is low in Hispanics and Asians.

Age

The incidence of prostate cancer increases markedly with age. In fact, the incidence is exponentially related to age.

• With advances in the treatment of heart disease, stroke, and other malignancies, men are living longer; this change in life expectancy increases the risk of having and dying from prostate cancer.
• Prostate cancer is rare in men younger than 50 years.
• One half of all cases occur in men older than 75 years. Maximum mortality rate is in those aged 85 years and older.

Anatomy

McNeal et al first proposed the histologic division of the prostate into an outer PZ, a central zone (CZ), and an inner TZ.⁴ In the young adult prostate, approximately 5% of prostatic glandular tissue is in the TZ located on both sides of the prostatic urethra. This is the area where benign hyperplasia develops in older patients.

The TZ is separated from the PZ and CZ by the surgical capsule, in which calcified corpora amylacea may be found. The CZ is situated at the base of the prostate, and the ejaculatory ducts reach the verumontanum by passing through CZ tissue. The CZ is relatively resistant to disease processes and constitutes approximately 25% of the glandular tissue of the prostate in the young adult. The PZ constitutes 70% of the prostate and lies on the posterior and lateral aspects of the gland surrounding the TZ. Its ducts drain into the urethra distal to the verumontanum. Approximately 75% of prostate cancers occur in the ultrasonic PZ, and 25% occur in the TZ.⁴

Presentation

Clinical presentation

Patients with prostate cancer may be asymptomatic. The diagnosis is usually made when abnormal digital rectal examination (DRE) results or elevated PSA levels are further investigated. Alternatively, cancer may be detected in tissue obtained during transurethral resection to treat a urinary outflow tract obstruction. Patients may present with symptoms of advanced disease, including weight loss, lethargy, bladder outflow obstruction, and bone pain. (Men with newly diagnosed prostate cancer and PSA levels of less than 20 ng/mL are unlikely to have skeletal metastases resulting from prostate cancer.)

Rhabdomyosarcomas of the prostate and pelvis represent a childhood malignant tumor. These appear as soft-tissue masses infiltrating the bladder and prostate. As such, they have a presentation and radiologic features completely different from those of prostatic adenocarcinomas.

PSA screening

PSA is a single-chain glycoprotein with a molecular weight of 34,000 daltons. Physiologically, PSA is produced in the prostatic ductal epithelium by both abnormal and normal prostate tissue, secreted into the prostatic ducts, then concentrated in the seminal plasma. This glycoprotein acts to liquefy the seminal coagulum formed with ejaculation. In serum, PSA reaches the circulation by diffusing through the prostatic stroma.

PSA screening is currently the single best test for prostate cancer and is widely used in the diagnosis of prostate cancer, but it does not help in determining whether the detected cancer will cause clinically significant disease. Whereas PSA is an excellent marker for the follow-up of patients with established prostate cancer, some men with prostate cancer may have normal PSA levels, a moderate elevation of the PSA level (4-10 ng/mL) has a low specificity for prostate cancer, and an elevated PSA level is not specific for prostate cancer. Elevated serum PSA levels may also be associated with prostatitis, prostate infarction, PIN, prostate biopsy, transurethral resection of the prostate, and urethral catheterization.

Because of the limitations of PSA screening, there have been efforts to improve its diagnostic specificity through the use of derivative indices such as PSA density, age-related PSA levels, TZ–PSA density, PSA velocity, free PSA levels, complexed PSA (cPSA) measurements, and free-to-total PSA ratios. The free-to-total PSA ratio measures both bound and free PSA as a percentage of total PSA and is a useful additional discriminator between cancer and benign pathology, especially in patients with moderately elevated serum PSA levels (4-10 ng/mL). This ratio is also useful in determining whether a repeat biopsy is appropriate in a patient with a moderately elevated PSA level whose initial systematic biopsy results are negative. The lower the percentage of free PSA, the higher the likelihood of cancer.

An assay for cPSA is now available and primarily measures alpha1-antichymotrypsin cPSA. Some studies have shown an increased specificity with the cPSA assay for the diagnosis of prostate cancer compared with the specificity of total PSA and free-total PSA. In the future, cPSA could conceivably replace total PSA measurements.

Serum PSA levels increase with age. The traditional upper limit of reference range levels of PSA is 4 ng/mL, but age-specific PSA reference range levels devised by Oesterling et al can be used.⁵ Age-related PSA reference range levels are as follows:

• Patients aged 40-49 years, 0-2.5 ng/mL
• Patients aged 50-59 years, 0-3.5 ng/mL
• Patients aged 60-69 years, 0-4.5 ng/mL
• Patients aged 70-79 years, 0-6.5 ng/mL

Serum PSA levels are lowered with finasteride treatment for benign prostatic hyperplasia (BPH), and this treatment must be considered when PSA levels are assessed and before the decision to perform prostatic biopsy is made.

Risk factors for prostate cancer

Possible risk factors for prostate cancer include dietary, genetic, occupational, racial, and other factors.

High fat consumption is a possible risk factor, and diets low in animal fat and protein decrease the risk. Substances that may offer some protection include vitamin E, selenium, and lycopene from tomato-based foods. Some authors have postulated that high soya consumption may be protective because of the ingestion of plant phytoestrogens.^{6, 7}

A family history of prostate or breast cancer is a risk factor, as is farming or exposure to radiation and cadmium. Blacks are at increased risk for prostate cancer. Neither alcohol consumption nor cigarette smoking is associated with a risk of prostate cancer.

Preferred Examination

Histopathologic evaluation is needed to diagnose prostate cancer after abnormal DRE results or elevated PSA levels are found. This evaluation is best performed with a sample obtained during biopsy guided with transrectal ultrasonography (TRUS), because the precise anatomic placement of the needle with TRUS is more accurate than digitally guided biopsy. Samples should include cores obtained during systematic biopsy, as well as those from focal ultrasonic PZ abnormalities.

Color or power Doppler ultrasonography may also be used to identify areas for biopsy under TRUS guidance. In the future, interventional magnetic resonance imaging (MRI) equipment may be used to guide needle biopsy of the prostate.

For the staging of prostate cancer, MRI is preferred to computed tomography (CT) scanning because it permits more accurate T staging. Both techniques can be used in N staging, and they have equivalent accuracy. Bone scintigraphy is used in M staging.

Limitations of Techniques

No optimal imaging technique has been developed for the demonstration of cancer within the prostate.

Currently, TRUS offers the best opportunity to demonstrate prostate cancer. It is widely available, has a relatively low cost, and provides the opportunity for precise and accurate needle biopsy of the gland. However, because many prostatic tumors are both isoechoic and multifocal, TRUS has major limitations in fully demonstrating prostate cancers. Furthermore, TRUS has low echotexture specificity because many pathologic conditions may demonstrate similar appearances as hypoechoic areas in the PZ of the prostate. For this reason, diagnostic assessment of cancer in the prostate must be made by means of the histopathologic interpretation of biopsy samples.

Current CT scanning techniques cannot demonstrate intraprostatic pathology, and signal-intensity changes in the PZ on MRI have a low specificity, as with TRUS.

Differential Diagnoses

Paget Disease

Other Problems to Be Considered

Hypoechoic area in prostate PZ on TRUS:

Cancer
Prostatitis
Prostatic infarct
PIN
Muscle around ejaculatory duct

Multiple sclerotic lesions within bone:

• Developmental: Bone islands, osteopoikilosis, Voorhoeve disease (osteopathia striata), and tuberose sclerosis (or tuberous sclerosis)
• Neoplastic: Metastases, lymphoma, osteomata, and myeloma (sclerosis may occur in as many as 3% of patients)
• Paget disease
• Vascular: Bone infarcts

References

• Paget Disease

• Prostate Health Center
• Cancer and Tumors Center
• Prostate Cancer Overview
• Prostate Cancer Causes
• Prostate Cancer Symptoms
• Prostate Cancer Treatment