Prostate Cancer Health Article

PROSTATE CANCER

Prostate cancer is the most common cancer in men and the second leading cause of cancer-related death in men. An estimated 191,000 cases of prostate cancer will be diagnosed in 2001 in the United States along with 30,500 prostate cancer-related deaths. The disease is detected by a combination of abnormal serum prostate-specific antigen (PSA) and digital rectal exam (DRE), and less often as an incidental finding after prostate resection for obstructive benign disease. It is uncommon at this time to diagnose prostate cancer in association with gross urinary obstruction, bleeding, or unexplained skeletal pain.

The disease is both hereditary and sporadic with one gene (HPC2), and several gene loci recently identified. The risk for developing prostate cancer increases twofold if a first-degree relative is affected and it further increases as more family members are afflicted (first- and second-degree relatives). Although no specific cause for prostate cancer has been identified, several factors contribute to the development of the disease. This includes the level of saturated animal fat in the diet, vitamin D production, and ethnic origin. African Americans have the highest rate of prostate cancer in the world, while it is the lowest in native Asians. The disease is more commonly seen after the age of fifty.

The natural history of prostate cancer is strongly driven by the tumor grade. The risk of prostate cancer death is low (less than 10%) in patients of almost all ages with low-grade disease; however, it is substantial for patients with moderate- or high-grade disease. Metastatic disease has a very predictable natural history, with a median survival of thirty to thirty-three months after diagnosis.

Prostate cancer is generally detected by an abnormal serum PSA determination and/or an abnormal DRE. The diagnosis is generally made by an ultrasound-guided needle biopsy of the prostate. These techniques have led to a stage shift in the disease, with the majority of lesions now detected in the clinically localized state. Contemporary treatments for clinically localized disease include watchful waiting, radical prostatectomy, radiation therapy (external beam or brachytherapy), or cryosurgery. Androgen ablation (removal of testosterone-like substances from the system) can be used alone or in combination with other modalities, and is the principle form of therapy for advanced disease.

The decision whether to treat the disease or observe the patient should be based on the probability of the patient reasonably living another five to ten years, and thus takes into account the patient's age and comorbid conditions. Surgery can be very effective and is generally employed in younger men where nerve-sparing surgery can be used to preserve erectile function. The major side effect is urinary incontinence, which can be significant in a small percentage of patients. External beam radiation therapy is also a standard form of therapy which is generally performed in older patients (over age seventy). It is usually well tolerated, but a small percentage of men can develop gastrointestinal side effects related to rectal irritation.

Brachytherapy refers to the implantation of radioactive pellets in the prostate gland, usually under ultrasound guidance. This technique has been employed for approximately a decade and is an effective form of therapy in men with appropriate lesions. The major side effect from this therapy is an increase in irritative voiding symptoms. An increasing body of knowledge suggests that the addition of androgen ablation may improve the outcomes of patients receiving radiation.

Approximately 20 percent of patients treated for localized disease will experience a rise in their PSA within five years. This group of biochemical- failure patients are an enlarging cohort of patients for which exact treatment recommendations are not available. Gross loco-regional disease has become less common in the PSA era. Prostate cancer generally metastasizes to the lymph nodes and the bones, with less common involvement of the visceral organs.

Prostate tumors are classically dependent on endogenous androgens as growth factors. The removal of androgens by castration (surgical or chemical) results in a regression of symptoms and measurable disease in 80 percent of patients. Unfortunately, there are androgen-resistant clones in most tumors, which makes this form of therapy palliative. Androgen ablation can be performed by the removal of the testicles or the administration of a luteinizing hormone releasing hormone (LHRH) antagonist.

Prostate cancer relapsing after androgen ablation is designated androgen independent prostate cancer. The median survival for such patients is approximately eleven months. Although newer chemotherapy agents are displaying activity in advanced prostate cancer, treatment is generally palliative. This is an area of intense clinical investigation and protocol therapy.

S. BRUCE MALKOWICZ

(SEE ALSO: Cancer; Prostate-Specific Antigen [PSA])