The management of localized prostate cancer remains one of the most controversial areas in urological oncology. While long-term survival is expected regardless of the initial treatment strategy, the probability of cure remains less than desirable. With an increasing number of patients diagnosed with localized at an earlier age, the issue of curability has become even more relevant. Long-term survival is no longer considered an adequate measure of success. In this review, we look at recent advances in radiation therapy of localized prostate cancer and their impact on the outcomes in this disease.

Traditional external beam radiation therapy

External beam radiation therapy was first used in the management of prostate cancer in the 1950s when megavoltage beam from cobalt-60 and linear accelerators became available. In the late 1960s and 1970s, Bagshaw and colleagues popularized external beam radiation therapy for prostate cancer at Stanford University and published excellent results using radiation therapy to the pelvis and prostate with doses of 65-68 GY. Indeed, for patients with no extracapsular tumor extension, the long-term survival paralleled that of the age-matched population. Following the work of Bagshaw and associates, many investigations report excellent results with clinical local tumor control rates of 65% to 88%. However, significant proportions were found to have positive post-treatment biopsies and local failures were observed. In the 1980s, improved surgical techniques resulted in a resurgence of radical prostatectomy, and revival of an old debate regarding the optimal management of localized prostate cancer. In the absence of data from randomized trials, this debate continues today. The patterns of care database in the United States and other studies, documented results of radiation therapy achieved across the United States and Canada. For patients with T₁ tumors, no excess mortality was observed up to 15 years after radiation therapy compared to an age-matched population. The 15-year overall survival was 40-46%, and the 10-year overall survival was 54-63%. At Stanford, Bagshaw report a 48% 15-year overall survival for patients with T₁-T₂ prostate cancer. However, in 20 years of follow-up, only 28%of those patients died of prostate cancer.

Standard dose radiation treatment was rarely associated with severe late toxicity. In a review of several large series of patients treated in the 1970s and 1980s, Shipley and co-workers observed 0-2.4% Radiation Therapy Oncology Group (RTOG) grade 4-5 toxicity rates with a 0-0.4% risk of treatment-related death. The risk of urinary incontinence was 0-1.5%, urethral structure 0-4.6% and persistent grade 2 diarrhea 0.4-3%.The risk of developing impotence was 33-61%, and was observed to increase with time. In the Massachusetts General Hospital data, the actual risk of impotence was 70% at 15 years; however, these data were collected retrospectively.

In older series, treatment failure was defined as the development of palpable tumor recurrence, or clinically evident metastatic disease. Clinical local control rates reported disease. Clinical local control rates reported with standard dose radiation therapy ranged between 70 and 85%. Experience with prostate-specific antigen (PSA) following radio therapy highlighted the problem that digital rectal examination underestimates local disease persistence. Even post-treatment biopsies may fail to detect the presence of residual microscopic prostate cancer.  The availability of PSA measurement has redefined the interpretation of failure following radiation therapy. Zagars and Pollack, in a large review of the MD Anderson Hospital experience, showed an increasing risk of PSA failure with increasing pre-treatment PSA levels. Similar data were reported from many other centers. In a recent review of the 794 patients treated with external beam radiation therapy at the Princess Margaret Hospital between 1989 and 1993, with a median follow-up of 4.2 years, the biochemical relapse-free survival was 45% at 7 years. The clinical local relapse-free survival was 68% and the clinical systemic relapse-free survival was 81% at 7 years. Univariate analysis identified increasing T category, Gleason score, pretreatment PSA level and PSA nadir as highly significant factors (<0,0001) predicting biochemical failure. Multivariate analysis identified pre-treatment PSA and T category as significant. The hazard ratios increased by 20% for each T category (T₁ vs. T_2a vs. T_2bvs.T_2c) and doubled for each increase in PSA category (0-4 vs. 4.1-10 vs. 10.1-20 vs.>20). For the best prognostic groups, the 5-year biochemical relapse-free survival (bRFS) was 70% for T₁, 85% for those with pretreatment PSA levels of 0-4 ng/ml. For the worst prognostic groups, the 5-year bRFS was 40% for T_2c, and 18% for patients with PSA levels of >20ng/ml.