Quantification and technique development to reduce ano-rectal toxicity in prostate radiotherapy.

Prostate cancer has an incidence of 8500/year in The Netherlands. One of the
curative treatment modalities, external beam radiotherapy (EBRT), has a
significant dose-response relationship. However, toxicity to surrounding
tissues is limiting dose-escalation. Especially ano-rectal toxicity has a
serious impact on patients quality of life. Given the high curation rates (and
long survival) of EBRT in localized prostate cancer, late toxicity is an
important issue.
Several reports have been made about relationships between the incidence and
severity of ano-rectal complaints and the radiation dose to the rectum and anal
canal. This means that lowering the dose to these organs reduces the risk of
ano-rectal toxicity. Modern EBRT techniques aim at high conformality, thereby
enabling the radiation oncologist to give a high dose to the target volume,
while selectively sparing the surrounding normal tissues. In the UMCN several
modalities are used to achieve this goal, like intensity-modulated radiotherapy
(IMRT), implantation of fiducial markers for postion verification and
-correction, and fusion of CT and MRI images for an optimal target volume
delineation. By applying these techniques, uncertainty margins are kept as
small as possible, thus keeping the volume of irradiated normal tissues as low
as possible. In addition, daily inserted endorectal balloons are used to spare
the rectal wall.
However, to further reduce the ano-rectal toxicity rates, it is important to
identify the exact pathophysiology and specific anatomic structures, involved
in its development to eventually modify irradiation techniques and selectively
spare these structures.
The first step in this proces is to objectify patients complaints by anorectal
manometry (to measure pressures in the anal canal, and compliance and
sensibility of the rectum) and rectosigmoidoscopy (to evaluate mucosal damage).

To objectify and quantify patients ano-rectal complaints to identify the exact
pathophysiology and involved anatomic structures.
Following this, irradiation techniques can be developed or modified to
selectively spare the abovementioned structures, thereby reducing the
ano-rectal toxicity rate in prostate EBRT.

Cohort study, following patients from baseline (i.e. before radiotherapy) to 2
years after treatment. Follow-up with questionnaires, ano-rectal manometries,
and rectosigmoidoscopies will be performed. Eventually, these data will be
correlated to subjective complaints and to the dose to specific anatomic
structures.

During a follow-up time of 2 years, patients are asked to fill out a
questionnaire (EPIC) five times at regular appointments on the outpatient
clinic, which will take approximately 10 minutes of their time.

In addition, in these 2 years 4 ano-rectal manometries will be performed
(baseline, and 6, 12, and 24 months post-radiotherapy, respectively). Each
investigation will take approximately 1 hour of time. Complications are very
rare; in literature some cases of rectal blood loss in patients with
pre-existing ulcerative colitis, and a rectal rupture in a patient with
previous rectal surgery are reported.

Six months, 12 months, and 24 months post-radiotherapy a rectosigmoidoscopy
will be done, taking 5-20 minutes of time. The complication rate of this
investigation is very low (0.14-0.25%) and consists of perforation. The
mortality rate of rectosigmoidoscopies alone is unknown. However, for
colonoscopies in general this is < 0.02%