Radiotherapy for Prostate Cancer: Conventional Dose Versus High Dose

Phase III Study for Prostate Cancer, Randomizing Between Two Radiation Dose Levels (68 Gy vs. 78 Gy) and Utilizing Three Dimensional Conformal Radiotherapy

3-D conformal radiotherapy offers the opportunity to reach higher tumor doses with acceptable complication rates compared to conventional radiotherapy. There are retrospective and preliminary prospective reports of a better local control / disease free survival (including PSA control) using higher tumor doses. A prospective randomised phase III study is required to validate these reports. The purpose of this randomized phase III study is to investigate and compare the tumor control and toxicity in prostate cancer patients treated to 68 Gy and 78 Gy;

Patients were stratified by hospital, treatment group, age and (neo)adjuvant hormonal therapy. Four treatment groups with specific radiation volumes were defined depending on the estimated risk of tumour involvement of the seminal vesicles (based on T-stage, initial PSA and Gleason Score or Differentiation Grade).The dose was delivered with daily fractions of 2 Gy, five times a week. The total duration of the treatment was 7 weeks for patients treated to 68 Gy and 8 week for 78 Gy.

Objectives:

• To test in a phase III randomised study the hypothesis that higher radiation doses lead to a higher freedom from failure rate for localized prostate cancer.
• To test the hypothesis that a higher freedom from failure rate leads to a longer disease-free survival and overall survival.
• To limit acute and late toxicity with respect to gastro-intestinal and urological toxicity.
• To evaluate different PSA related endpoints for local failure and distant metastasis.
• To establish a database of patients treated to escalated doses with Dose Volume Histograms of the normal tissues at risk for each individual patient and common toxicity endpoints.
• To validate a model to estimate normal tissue complication probabilities (NTCPs) of rectum and bladder, based on the above-mentioned database, and to obtain reliable parameter values for NTCP estimations.

Inclusion Criteria:

• locally confined adenocarcinoma of the prostate
• all T-stages with a PSA < 60ng/ml, except any T1a tumor and well-differentiated (or Gleason score < 5) T1b-c tumors with PSA-levels ≤ 4 ng/ml
• Karnofsky Performance Status of 80 or more

Exclusion Criteria:

• distant metastases
• positive regional lymph nodes proven by surgical or cytological sampling
• on anticoagulants
• previous prostatectomy
• previous pelvic irradiation