Chapter 146

Prostate Cancer

Kenneth Peterson

Definition and Epidemiology

Other than skin cancer, cancer of the prostate is the most common malignant neoplasm in men in the United States and the second leading cause of cancer death in men of all races and Hispanic origin populations.¹ The National Cancer Institute estimated that in 2014 the United States had 233,000 new cases diagnosed and 29,480 deaths from prostate cancer.² One in seven men in the United States will be diagnosed with prostate cancer in his lifetime, and more than 2 million American men are living with prostate cancer.³ Risk factors for prostate cancer include advancing age, African-American race, and a positive family history of prostate cancer. Geography is considered a risk factor; prostate cancer is more common in Caribbean men of African ancestry and men living in North America, northwestern Europe, and Australia. The majority of cases are diagnosed in men older than 65 years, with incidence rates higher in African-American men than in white men.² The mortality rate of African-American men is estimated to be twice that of white men.² As a result of early, effective screening and the aging of the U.S. population, the number of prostate cancer cases diagnosed has increased; however, deaths from prostate cancer have decreased significantly in recent years, and the majority of men diagnosed with prostate cancer do not die of the disease.²^,³

Pathophysiology

The most common type of prostate cancer is adenocarcinoma. It develops in the acinar glands located in the posterior peripheral zone of the prostate. Histologic grading is an important predictor of prognosis. The Gleason system incorporates clinical and physiologic parameters for grading of the malignant neoplasm.⁴ Tumors can arise in one or both lobes of the prostate and can spread within the prostate, through the prostatic capsule, and through the seminal vesicles or the base of the bladder, with metastasis occurring through the lymphatic and circulatory systems.

Clinical Presentation

Presenting symptoms of prostate cancer may include urinary hesitancy, urgency, nocturia, frequency, and hematuria, although the patient is usually asymptomatic in early stages of the disease. Symptoms tend to increase in intensity during a 1- to 2-month period, which is different from the slow, gradual progression in symptoms that occurs in benign prostatic hyperplasia (BPH). In more advanced disease, presenting symptoms may include back pain, impotence, and other bone pain that suggests metastasis. Other symptoms of metastasis include weight loss, constipation, malaise, hematuria, and rectal pain or symptoms related to nerve root compression, such as paresthesias or extremity weakness.

Rarely, prostate cancer can be non–prostate-specific antigen (PSA) producing, and tumor burden will not correlate with PSA values. These patients will have the same presentation as others, with symptoms of bone pain or obstruction, and will likely have abnormal digital rectal examination (DRE) findings but a low PSA level. Patients with signs and symptoms of prostate cancer should be referred to a urologist for evaluation, even in the presence of a normal PSA level.

Physical Examination

The DRE is used to detect initial physical abnormalities of the prostate gland. A firm nodule on rectal examination, induration, or a stony, asymmetric prostate is suggestive of prostate cancer. In early-disease stage, the findings on prostate examination will generally be normal.

Diagnostics and Differential Diagnosis

Measurement of the PSA level combined with DRE if elevated is considered the most sensitive and specific screening method for prostate cancer. Some controversy exists regarding initial PSA screening and interval testing. The American Urological Association (AUA) recommends that men who are considering prostate screening should discuss the benefits and harms of testing with their health care providers. The American Cancer Society recommends that men have the opportunity to make an informed decision with their care provider about prostate cancer screening.⁵ The U.S. Preventive Services Task Force continues to support the recommendation against PSA-based screening for prostate cancer. The recommendation applies to all men in the general U.S. population regardless of age.⁶ (See Life Span Considerations for age-specific screening recommendations.)

PSA is a protease enzyme secreted by the prostate gland, and levels may be elevated in both benign and malignant conditions of the prostate. A prostate level below 4 ng/mL is considered normal, although a prostate tumor may be present with a PSA level below 4 ng/mL. Algorithms exist to adjust normal values for age and race. In addition, some medications (e.g., finasteride) can decrease PSA values, thus requiring adjustment. Values of 4 to 10 ng/mL may be seen in early prostate cancer and other benign conditions; values above 10 ng/mL suggest prostate cancer. The use of the free PSA test and determination of PSA velocity (rate of rise) may increase specificity for prostate cancer, especially if the PSA level is elevated. A rate of rise of more than 0.75 ng/mL per year is considered highly sensitive for prostate cancer.⁷^,⁸ Different age-specific reference ranges are sometimes considered, especially in African-American men, because cases in this population might be missed with use of the traditional reference ranges.

Similar to decisions about when PSA screening should occur, the decision regarding when to perform tissue biopsies for prostate cancer diagnosis confirmation remains controversial. In men older than 60 years, if the PSA level is higher than 4.0 ng/mL or findings on DRE are abnormal, transrectal ultrasound (TRUS) of the prostate with TRUS-guided biopsy is recommended. TRUS allows guided biopsy of suspicious hypoechoic areas. In younger men, biopsy is considered if the PSA level is above 2.6 ng/mL.

In cases with a positive finding on biopsy of the prostate and a PSA level above 10 µg/L, a radionuclide bone scan may be necessary to determine the presence of bone metastases. Magnetic resonance imaging (MRI) of the abdomen and pelvis is important to assess the regional lymph nodes and metastasis. A chest x-ray study can exclude metastasis to the lungs. An elevated alkaline phosphatase level suggests bone metastasis, and an elevated acid phosphatase level suggests prostatic metastasis.

The differential diagnosis includes BPH and prostatitis when there is an abnormal DRE finding and PSA test result. Other potential differential diagnoses include bladder cancer, urinary tract infection, and urethral stricture.

Based on data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, the rate of death from prostate cancer did not differ significantly by whether the prostate cancer screening test used was PSA or DRE.⁹

Diagnostics

Prostate Cancer

Laboratory