Adenocarcinoma of the prostate is the most common malignancy in men > 50 yr in the USA; the incidence increases with each decade of life. There are about 209,900 new cases/yr in the USA (1997 estimate). Sarcoma of the prostate is rare, occurring primarily in children. Undifferentiated prostate cancer, squamous cell carcinoma, and ductal transitional carcinoma also occur and respond poorly to the usual measures of control. Hormonal influences undoubtedly play a role in the etiology of adenocarcinoma but almost certainly no role in sarcoma, undifferentiated cancer, squamous cell carcinoma, or ductal transitional cell carcinoma.

Prostate cancer is usually glandular, similar to the histologic configuration of normal prostate. Small cell proliferation and large nucleoli are characteristic. Grading is based on architectural patterns and is commonly reported as the Gleason score: the primary (most prevalent) grade (1-5) plus the secondary (next most prevalent) grade (1-5); thus, it ranges from 2 (very well differentiated) to 10 (very poorly differentiated). Staging is defined in Table 233-1.

Symptoms, Signs, and Diagnosis
Prostate cancer generally is slowly progressive and may cause no symptoms. In late disease, symptoms of bladder outlet obstruction, ureteral obstruction, and hematuria may appear. Metastases to the pelvis, ribs, and vertebral bodies may cause bone pain. Locally advanced prostate cancer may exhibit extension of induration to the seminal vesicles and fixation of the gland laterally.

Prostate cancer should be suspected on the basis of abnormal digital rectal findings, hypoechoic lesions on transrectal ultrasound (TRUS), or elevated levels of serum prostate-specific antigen (PSA). However, diagnosis requires histologic confirmation, most commonly by TRUS-guided transrectal needle biopsy, which can be done in the clinic without anesthesia. Involvement of perineural lymphatics, if present, is diagnostic. Carcinoma is diagnosed incidentally when malignant changes are found in the tissue removed during surgery for suspected benign prostatic enlargement.

Prostate cancer frequently produces osteoblastic bony metastases. Detection on bone scan or x-ray in the presence of a stony hard prostate is usually diagnostic.

TRUS may provide information for staging, particularly relative to capsular penetration and seminal vesicle invasion. Elevated serum acid phosphatase on Roy test (an enzymatic method) correlates well with the presence of metastases, particularly in lymph nodes. This enzyme may also be elevated in benign prostatic hyperplasia (slight elevation after vigorous prostatic massage), multiple myeloma, Gaucher's disease, and hemolytic anemia. Research protocols are evaluating the potential role of reverse transcriptase-polymerase chain reaction (RT-PCR) assays for circulating prostate cancer cells in staging and prognosis.

Although acid phosphatase and PSA levels decline after treatment and rise with recurrence, PSA is the most sensitive marker for monitoring cancer progression and response to therapy. However, because serum PSA is moderately elevated in 30 to 50% of patients with benign prostatic hyperplasia (depending on prostate size and degree of obstruction) and in 25 to 92% of those with prostate cancer (depending on tumor volume), its role in early detection and staging is still being evaluated. Significantly elevated PSA levels suggest extracapsular extension of tumor or metastases. Newer assays that determine the proportion of free vs. bound PSA may decrease the frequency of biopsies in patients without cancer.

Stony hard induration or a nodule of the prostate on digital rectal examination suggests malignancy and must be differentiated from granulomatous prostatitis, prostatic calculi, and other more unusual prostatic diseases. However, a normal prostate on digital rectal examination does not exclude carcinoma.

Prognosis and Treatment
Long-term local control--even cure--is possible in many patients. However, the potential for cure, even in patients with clinically localized cancer, depends on factors such as grade, stage, and pretreatment PSA level. For patients with low-grade, organ-confined tumors, survival is virtually identical to that for age-matched controls without prostate cancer.

Some older patients with localized prostate cancer, particularly if it is well-differentiated, may require no treatment (ie, watchful waiting), because the risk of death from other causes is greater than that from prostate cancer. Most patients, however, elect to undergo definitive therapy with radical prostatectomy or radiotherapy. Radical prostatectomy is probably optimal for younger patients with long life expectancy; they have the lowest risk of urinary incontinence (about 2%), and about 50% will be able to maintain erectile potency (if at least one neurovascular bundle can be spared). Radiotherapy may offer comparable results, especially in patients with low pretreatment PSA levels. Standard external beam radiotherapy generally delivers 70 Gy (7000 rad) in 7 wk. Conformal three-dimensional techniques safely deliver doses approaching 80 Gy (8000 rad), and early data indicate that the rate of local control is higher. Whether interstitial irradiation (seed implants) will produce equivalent results is being evaluated.

An asymptomatic patient with a locally advanced tumor or metastases may benefit from hormonal therapy with or without adjuvant radiotherapy. Hormonal therapy rarely uses exogenous estrogens, which pose a risk of cardiovascular and thromboembolic complications. Bilateral orchiectomy or medical castration with luteinizing hormone-releasing hormone agonists decreases serum testosterone equivalently. Some patients may benefit from the addition of antiandrogens for total androgen blockade. Local radiotherapy is usually palliative in patients with symptomatic bone metastases. There is no standard therapy for hormone refractory prostate cancer; cytotoxic and biologic agents are being investigated and may offer palliation and prolonged survival. However, their superiority over corticosteroids alone has not been proved.