Current concepts in the management of prostatic cancer

In most western countries, carcinoma of the prostate is the second most frequent cause of cancer death following carcinoma of the lung. In the pathogenesis of clinical carcinoma of the prostate, several mutational steps can be distinguished which correlate with subclinical and clinical situations. Focal carcinoma is identified in autopsy series at least 500-1,000 times more than is appreciated on clinical grounds alone. Still, focal carcinoma must be considered the precursor of all clinical disease. At least three mutational steps must be involved in the pathogenesis: the development of focal carcinoma from normal cells, the progression to hormone-dependent clinical carcinoma, and the progression to hormone-independent carcinoma. The geographic variation of these events suggests that exogenous factors play an important role in the pathogenesis of prostatic cancer. Focal, noninvasive carcinoma is found in the clinical situation incidentally upon treatment of obstruction in 8-12% of cases with benign prostatic hyperplasia. This lesion is usually not treated aggressively. The incidence of clinical prostatic carcinoma is strictly age-related. Because the tumor largely occurs after age 50, and competing causes of death play an important role, only about 50% of all patients with clinical prostatic carcinoma are likely to die of this disease. Prostatic carcinoma is most frequently diagnosed in the metastatic state (40-50%). The remainder are locally confined with an incidence of lymph node metastases of roughly 35%. Tumors diagnosed in the metastatic state have a distinctly poorer prognosis than tumors diagnosed as potentially curable lesions. Metastatic prostatic carcinoma is usually managed by means of androgen suppression. Hormone-dependent human tumor lines in nude mice suggest that endocrine-dependent cells are not killed by androgen withdrawal, but remain dormant and can be restimulated to grow. In the same sense, management of prostatic carcinoma appears to be palliative. Patients die of prostatic carcinoma because hormone-independent cell populations develop and cannot be influenced by hormonal management. Still-open questions concerning endocrine management are the timing of androgen withdrawal (early versus delayed) and the degree of androgen withdrawal (total versus subtotal). Luteinizing hormone-releasing hormone (LHRH) agonists and antiandrogens allow endocrine management with minimal side effects. Prolongation of life and cure can only be expected from simultaneous effective treatment of hormone-independent tumor cell populations.