Treatment Option Overview
Candidates for definitive radiation therapy must have a confirmed pathological diagnosis of cancer that is clinically confined to the prostate and/or surrounding tissues (stage I, stage II, and stage III). Patients should have a computed tomographic scan negative for metastases, but staging laparotomy and lymph node dissection are not required. Prophylactic radiation therapy to clinically or pathologically uninvolved pelvic lymph nodes does not appear to improve overall survival (OS) or prostate cancer-specific survival as seen in the RTOG-7706 trial, for example.[Level of evidence: 1iiA] In addition, patients considered poor medical candidates for radical prostatectomy can be treated with an acceptably low complication rate if care is given to the delivery technique. Long-term results with radiation therapy are dependent on stage. A retrospective review of 999 patients treated with megavoltage radiation therapy showed cause-specific survival rates to be significantly different at 10 years by T-stage: T1 (79%), T2 (66%), T3 (55%), and T4 (22%). An initial serum prostate-specific antigen (PSA) level higher than 15 ng/mL is a predictor of probable failure with conventional radiation therapy. Several randomized studies have demonstrated an improvement in freedom from biochemical (PSA-based) recurrence with higher doses of radiation therapy (78 Gy-79 Gy) as compared to conventional doses (68 Gy-70 Gy).[18,19,20][Level of evidence: 1iiDiii] The higher doses were delivered using conformal techniques. None of the studies demonstrated a cause-specific survival benefit to higher doses; however, an ongoing study through the Radiation Therapy Oncology Group will be powered for OS.
Interstitial brachytherapy has been employed in several centers, generally for patients with T1 and T2 tumors. Patients are selected for favorable characteristics, including low Gleason score, low PSA level, and stage T1 to T2 tumors. Information and further study are required to better define the effects of modern interstitial brachytherapy on disease control and quality of life and to determine the contribution of favorable patient selection to outcomes.[Level of evidence: 3iiiDiv] Information about ongoing clinical trials is available from the NCI Web site.
There is interest in the use of novel radiation techniques (e.g., intensity-modulated radiation therapy, proton-beam therapy, cyber knife) for the treatment of prostate cancer. Although proton therapy could theoretically improve the therapeutic ratio of prostate radiation, allowing for an increase in dose to the tumor without a substantial increase in side effects, no randomized controlled trials have been conducted to compare its efficacy and toxicity with those of other forms of radiation therapy.
Asymptomatic patients of advanced age or with concomitant illness may warrant consideration of careful observation without immediate active treatment.[22,23,24] One population-based study with 15 years of follow-up (mean observation time = 12.5 years) has shown excellent survival without any treatment in patients with well-differentiated or moderately well-differentiated tumors clinically confined to the prostate, irrespective of age. None of these men were detected by PSA screening, since PSA was not available at the time. The patient cohort was followed for a mean of 21 years after initial diagnosis. The risk of prostate cancer progression and prostate cancer death persisted throughout the follow-up period. By the end of follow-up, 91% of the cohort had died; 16% had died of prostate cancer. A second, smaller population-based study of 94 patients with clinically localized prostate cancer managed by a watch and wait strategy gave very similar results at 4 to 9 years of follow-up. In a selected series of 50 stage C patients, 48 of whom had well-differentiated or moderately well-differentiated tumors, the prostate cancer-specific survival rates at 5 and 9 years were 88% and 70%, respectively.