**3. Implications and summary of findings of studies and conclusion(s)**

The data presented in this chapter, based on studies spanning over two decades examining gastrointestinal effects of pelvic radiotherapy for prostate and gynecological cancer, indicate that despite advances in radiotherapy technology, anorectal dysfunction persist or progressively worsen over a period of 5–10 years after treatment. The multiple deteriorations in anorectal function, consisting of weakness of

the anal sphincters, stiffness of the rectal wall and consequent increase in rectal sensitivity, result in 50% of patients being housebound and only able to go out if there is a toilet nearby. The studies also show that the prevalence of rectal bleeding is half that of urgency of defaecation. In addition, results of the first randomized trial of Argon Plasma Coagulation Therapy versus topical formalin for intractable rectal bleeding after radiotherapy for prostate cancer indicate that durable control is achieved in 94–100% of patients after a median of 2 sessions of either treatment, only 7% of patients requiring re-treatment after a median follow-up of 9 years [15]. In contrast, therapeutic options for anorectal dysfunction are limited to medications such as loperamide and nicardipine based on pathophysiological evaluation of bowel disorders which include chronic radiation proctitis. For example, nicardipine which increases the rectal threshold for desire to defecate in patients with irritable bowel syndrome and reported to be effective in the treatment of urgency of defecation has been proposed for the treatment of urgency of defecation associated with chronic radiation proctitis since threshold volumes for desire to defecate are also reduced in CRP [14]. Similarly, loperamide, by increasing basal anal and squeeze pressures in patients with fecal incontinence of diverse aetiologies including radiation bowel disease, has been proposed for the treatment of fecal incontinence associated with CRP [14]. However, loperamide reduces stool bulk potentially increasing the risk of rectal bleeding and a lower dose than that prescribed for other bowel disorders is recommended [2]. Whilst the most advanced radiation treatment technique of intensity modulated radiation therapy (IMRT) was not used in the studies here, the prevalence of anorectal toxicity after IMRT for prostate cancer has been reported to be 65%, worse or no different from that reported in studies using less advanced treatment techniques including those reported here [1, 2, 6, 14, 16]. A likely explanation for the failure of IMRT to reduce anorectal dysmotility after treatment is that its underlying pathogenesis is damage to neural tissue in the bowel wall and/or the pudendal nerves [2, 16]. As discussed in the editorial accompanying

#### **Figure 6.**

*Transverse (top) and sagittal dose distributions of IMRT plans for prostate cancer without (left) and with (right) endorectal balloon in place. Contours: Rectal wall (green), anal wall (purple). (From Smeenk et al. [5], with permission).*

*Pathophysiology, Natural History and Approaches to Treatment and Prevention of Radiation… DOI: http://dx.doi.org/10.5772/intechopen.99269*

the published findings of the final study of this chapter [19], the pudendal nerves are not considered as normal tissues at risk of radiation damage and therefore could potentially receive the same if not higher doses of radiation as the prostate target of irradiation. Radiation dose constraints for normal tissues at risk including the pudendal nerves have been proposed (Section 2.4 above) and if applied now that IMRT has been adopted almost universally, patients who need pelvic radiotherapy for urological and gynecological cancer can look forward to a future free of distressing bowel morbidity. Furthermore, the daily insertion of endorectal balloons during radiotherapy (**Figure 6**), which have been shown to be very well tolerated and to further reduce radiation exposure of the rectal and anal wall (and the anatomically closely related pudendal nerves) by IMRT [5] means a bowel complication free cure of pelvic malignant disease can be realistically achieved in the foreseeable future.

### **Acknowledgements**

The work reported in this chapter is based on 4 published studies of the effect of radiotherapy for prostate and gynecological cancer on anorectal function. All studies were performed in the Departments of Radiation Oncology, Gastroenterology and Colorectal Surgery, Royal Adelaide Hospital, Australia, affiliated with the University of Adelaide with substantial technical expertise for the performance of pudendal nerve terminal motor latency provided by the Department of Gastroenterology and Surgery, Flinders Medical Centre, Australia, affiliated with Flinders University.

The names of the contributors to the 4 published studies, listed as co-authors in the references section, are acknowledged although none of these co-authors contributed to the writing of this chapter.
