Localized carcinoma of the prostate (Stages T1B, T1C, T2, and T3). Review of management with external beam radiation therapy

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Abstract
Background. Optimal treatment for patients with localized carcinoma of the prostate is controversial. Radiation therapy is an established modality in the management of these patients, and several reports indicate the results are comparable to those achieved with radical prostatectomy. Recently effectiveness of therapy for carcinoma of the prostate is being evaluated in light of posttreatment prostate-specific antigen (PSA) determinations. Methods. A review was performed of multiple publications and data from selected institutions with large experience in the management of carcinoma of the prostate. Survival and clinical incidence of local recurrence and distant metastases were analyzed as well as preliminary data on postirradiation PSA levels. Factors that affect the outcome of therapy and relevant clinical trials are discussed. Results. Reported differences in the age of patients treated with radical prostatectomy (59-63 years), irradiation (63-69 years), or observation (69-75.5 years) were identified. The effect of surgical staging on outcome of irradiation was significant. In multiple series of patients clinically and radiographically staged, the 5-year disease-free survival (DFS) with external irradiation was 95-100% for clinical stage T1a, 80-90% for Stage T1b,c, and 50-70% for clinical Stage T3. A correlation has been identified between the initial PSA levels and the probability from freedom of chemical failure (PSA elevation) after definitive irradiation. In five series comprising 814 patients with Stage T1c and T2 tumors, the DFS (end point chemical failure) was 95%, with initial PSA of less than 4 ng/ml, 83-92% with 4.1-10 ng/ml, 35-85% with 10.1–20 ng/ml, and 10-63% with PSA higher than 20 ng/ml. In the various series, follow-up ranged from a median of 1.5 years to a minimum of 4 years. In two series of 225 and 201 patients receiving doses of 7500–8000 cGy, less morbidity has been observed with three-dimensional treatment planning conformal radiation therapy than with conventional irradiation. New directions for future clinical trials are discussed, including dose escalation studies; use of high linear energy transfer to improve locoregional tumor control; and combination of irradiation and androgen suppression to enhance local tumor control, decrease distant metastasis, and improve survival. Preliminary results of a randomized study recently reported by RTOG strongly suggest that the use of goserelin acetate and flutamide decreases the incidence of clinical local recurrence (12.4% in 225 patients) compared with a control group treated with irradiation alone (25.2% in 230 patients) and enhances disease-free survival. Conclusions. Although modern approaches to the management of patients with localized carcinoma of the prostate with irradiation are effective, investigators must continue to critically assess policies of treatment, develop appropriately designed prospective clinical trials, and define the optimal management of patients with localized carcinoma of the prostate.

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