Dose–Volume Constraints to Reduce Rectal Side Effects From Prostate Radiotherapy: Evidence From MRC RT01 Trial ISRCTN 47772397

Purpose

Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose–volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (≥50 Gy). Evidence is emerging that lower doses could also be important.

Methods and Materials

Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose–volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity.

Results

A statistically significant dose–volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30–70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose–volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose–volume constraints from the set of V30≤80%, V40≤65%, V50≤55%, V60≤40%, V65≤30%, V70≤15%, and V75≤3%.

Conclusion

Considering the entire dose distribution to the rectum by applying dose–volume constraints such as those tested here in the present will reduce the incidence of late rectal toxicity.

Prostate radiotherapy, rectal complications, late toxicity, dose–volume constraints