Prostate Cancer Management

Alternate Names : Adenocarcinoma of the Prostate

Prostate Cancer Management

There is no known preventive therapy of prostate cancer. A large national cooperative trial of the daily administration of finasteride, an inhibitor of 5α-reductase which converts testosterone to the multifold more potent dihydrotestosterone, is currently in progress. The study seeks to determine whether finasteride reduces the prevalence of biopsy-proven prostate cancer in men 55 years of age or older who have taken the drug for 7 years.

The election of specific therapy for prostate cancer requires the histopathologic diagnosis of the disease. Because the therapies of prostate cancer may induce important disabilities or toxicities, the ensurance of the presence of malignancy is paramount. In addition, the occasional identification of atypical forms of prostate cancer (e.g., sarcomas or small cell tumors) may warrant the avoidance of hormone ablation therapies in favor of other management approaches.

It is important that the management of prostate cancer is linked to the presenting stage of the disease (Tables 97-1 and 97-2). In general, surgery or radiation therapy is applied to disease that is still confined to the prostate gland. For cancer that has transgressed the capsule of the gland, spread to pelvic lymph nodes, or disseminated to bone or other organs, hormonal ablation or systemic chemotherapy is often used. For patients anticipating receipt of local therapy for prostate cancer, staging pelvic lymphadenectomy is recommended. This procedures has no intrinsic therapeutic value but provides important evidence of disease dissemination to pelvic (obturator and iliac) lymph nodes and ultimately to occult distant sites.

Patients commonly have clinically occult prostate cancer detected on pathologic examination of tissue obtained during transurethral resection of the prostate for BPH (T_1a or T_1b; stage A) or following needle biopsy of the prostate following elevated PSA level (T_1c; stage A).

For stage A1 (T_1a) prostate cancer, progression of disease is infrequent and removal of the prostate has not been shown to provide a survival benefit. Observation is a reasonable approach in such individuals unless the patient is young (<60 years of age). If the patient is otherwise expected to live many additional years, radiation may eradicate microscopic residual disease.

For stage A2/B (T_1b, T_1c, T₂) prostate cancer, radical prostatectomy and irradiation (external beam with or without interstitial therapy) are essentially equivalent therapies. Adequate comparisons of radiotherapy versus surgery that provide convincing evidence of survival differences in balanced patient samples have not been performed. Both therapies can cause substantial morbidities: prostatectomy is accompanied by risks of anesthesia and surgical complication, urinary incontinence, and/or sexual impotence; radiation may induce prolonged proctitis, cystitis, urethral stricture, and/or sexual impotence. Procedures with potentially less morbidity and results equivalent to prostatectomy or external beam radiotherapy include transperineal brachytherapy or cryosurgery. Data about long-term overall and disease-free survivals for these latter techniques are pending. In addition, these techniques require comparison in clinical trials to the standard management of early-stage prostate cancer before they may be accepted as a standard of care.

Stage C (T₃) prostate cancer represents a substantial therapeutic predicament for the treating physician. Attempted radical prostatectomy often reveals evidence of extracapsular extension of cancer (pathologic stage C). Clinical examination of the prostate may also suggest extracapsular extension (clinical stage C). The best therapy for this stage is unknown, and local therapies are regarded as beneficial to a minority of such patients, since most are destined to relapse. Surgery appears to have limited effectiveness in this setting due to a high frequency of positive surgical margins following attempted resection.

Radiation is not uncommonly applied to patients with stage C cancer, either alone or as adjunct to surgical resection. Hormonal ablation is frequently employed, particularly in the elderly individual for whom surgical management or radiation therapy risks serious morbidity.

Stage D₁ (any T, N_1-3) is characterized by the presence of metastases to pelvic lymph nodes. The detection of pelvic lymph node metastases defines an expectation of disseminated prostate cancer within 5 years. Currently controversy exists about the need for early or delayed therapy in patients with stage D₁ disease. It has not been definitively shown that patients have any detrimental survival outcome with delay of hormonal ablation therapy until the appearance of disseminated disease. Consequently, expectant observation is a common approach following pelvic lymphadenectomy and detection of lymph node metastasis.

Stage D₂ prostate cancer encompasses metastatic disease to all extrapelvic sites. This stage of cancer is classically managed in its initial phases with androgen ablation. Bilateral orchiectomy remains the standard against which all alternative hormone ablation methods are compared. The advantages of orchiectomy include accomplishment of androgen ablation with a single procedure, immediate effect, and avoidance of continued therapy to sustain its effectiveness. No competing ablative therapy has been shown to exceed orchiectomy for long-term effectiveness. As an alternative, prostate cancer patients with metastatic disease may elect "total androgen blockade" (Table 97-3). Total androgen blockade utilizes a parenterally administered luteinizing hormone-releasing hormone (LHRH) agonist (goserelin acetate or leuprolide acetate) plus an orally administered antiandrogen (flutamide or bicalutamide). The LHRH agonist diminishes LH and follicle-stimulating hormone blood levels and ultimately yields castrate blood levels of androgens. The antiandrogens block androgen receptors and thereby block the modest androgenic contribution from adrenal hormone synthesis. Although the major hormone ablation therapies may accomplish dramatic tumor regression, symptom relief, and perhaps survival benefits, most patients are destined to develop resistance to such therapies. Resistance to hormone ablative therapy (i.e., hormone refractory) has ominous meaning insofar as restoration of antitumor response with alternative therapies occurs in a minority of patients, and survival expectation is materially truncated. Alternative hormone ablation therapies include diethylstilbestrol, aminoglutethimide with hydrocortisone, flutamide withdrawal, or ketoconazole.

Chemotherapy is reserved for those patients who are hormone refractory (defined as failure to manifest antitumor response following one or two hormone ablative therapies). Objective antitumor responses are infrequent with chemotherapy, and survival is rarely impacted. Agents that have shown some utility include estramustine, paclitaxel (Taxol), vinblastine, doxorubicin, cisplatin, and etoposide.

Important palliative approaches for patients with symptomatic bone metastases include radiopharmaceuticals such as strontium 89 (Metastron). Antitumor agents with some promise in the treatment of advanced prostate cancer include suramin, an antitrypanosomal agent that inhibits growth factor binding to receptors on prostate cancer cells.