The feasibility of dose escalation with three-dimensional conformal radiotherapy in patients with prostatic carcinoma

To evaluate the acute morbidity, late toxicity, and response to treatment in patients with prostate cancer treated on a phase I dose-escalation study with three-dimensional conformal radiotherapy.

A group of 432 patients with stages T1c-T3 prostate cancer were treated with three-dimensional conformal radiotherapy targeting the prostate and seminal vesicles, but effectively excluding the surrounding normal tissue structures from the high-dose volume. A minimum tumor dose of 64.8 to 66.6 Gy was given to 89 patients (20%), 70.2 Gy to 199 patients (46%), 75.6 Gy to 98 patients (23%), and 81.0 Gy to 46 patients (11%).

Treatment was well tolerated, and the acute toxicities and long-term complications observed were of minimal severity (grade 1 or 2) regardless of dose. Acute grade 2 rectal symptoms were observed in 15% of patients, whereas 40% developed grade 2 urinary symptoms. Among patients who received from 64.8 to 70.2 Gy, the 2-year actuarial likelihood of grade 2 late toxicity was 2% for rectal and 1% for urinary complications, compared to 11% and 5%, respectively, for those treated with doses ranging from 75.6 to 81 Gy. Only three patients (0.7%) have so far developed severe (grade 3 or 4) late urethral or rectal complications. The rate of prostate-specific antigen normalization from abnormal pretreatment levels to a value of < or = 1.0 ng/mL was used as an endpoint to evaluate the initial response to treatment. When the analysis was restricted to patients with pretreatment prostate-specific antigen levels of < or = 20 ng/mL, patients who received 70.2 Gy had a significantly higher rate of prostate-specific antigen normalization than patients who received 64.8 to 66.6 Gy. Evaluation of the prostate-specific antigen response at 75.6 Gy and 81.0 Gy was not possible because of the short follow-up time in many of these patients.

Three-dimensional conformal radiotherapy technique has made it possible safely to escalate radiation doses to unprecedented levels in patients with prostatic cancer. Preliminary evidence for an improved initial prostate-specific antigen response with higher doses indicates a potential for an improved therapeutic ratio with the three-dimensional conformal radiotherapy approach.