PRELIMINARY-RESULTS OF A HYPERFRACTIONATED DOSE-ESCALATION STUDY FOR LOCALLY ADVANCED ADENOCARCINOMA OF THE PROSTATE

The objective of this study was to build on our experience with 3-D conformal radiotherapy (CRT) by using a hyperfractionated dose escalation scheme to maximize the therapeutic ratio between improved local control and reduced morbidity in patients with locally advanced prostate cancer. Twenty patients with locally advanced (T3, T4) adenocarcinoma of the prostate were treated with a hyperfractionated radiotherapy schedule. All fields were designed with a conformal therapy based beam's eye view, 3-D planning system. The pelvic lymph nodes received 1.8 Gy/day to a total dose of 45 Gy in 5 weeks. Using partial transmission blocks, the prostate and periprostatic tissues received 1.3 Gy twice daily (minimum interval of 6 h) to a total dose of 78 Gy in 6 weeks. The dose was chosen by calculating the biologically effective dose (BED) which would produce the same effect in late reacting tissue but an increase for the tumor as our standard dose of 69 Gy delivered in 1.8-2.0 Gy fractions. The alpha/beta chosen for late damage was 3 Gy and 10 Gy was used for the tumor. All 20 patients completed the planned course of treatment. Although an increase in the tumor BED would be expected to result in increased acute effects, no significant worsening of acute side-effects was observed compared with standard treatment. All patients had only mild (Grade 1) rectal or bladder toxicity during treatment. One patient had an exacerbation of diverticulitis during treatment requiring hospitalization for antibiotics but completed treatment on schedule. In patients with locally advanced prostate cancer, a hyperfractionated schedule has demonstrated that it is feasible to deliver higher doses of radiation (78 Gy) with minimal acute toxicity. Further follow-up will demonstrate whether the incidence of late complications will be acceptable and whether histologic sterilization of the prostate cancer will be enhanced.