The main toxicities of treatment are gastrointestinal with symptoms caused by radiation enteritis (injury to small and large intestines) and proctitis (injury to rectum and anal canal). Acutely, no additional diagnostic work-up is needed if symptoms are consistent; however, in the late/chronic setting, endoscopy and biopsy should be performed to rule out other etiologies. In the acute setting, management includes anti-diarrheal medications such as imodium (loperamide) or lomotil (diphenoxylate/atrophine). Opioids, in addition to helping with pain, can also slow down bowel movements.

Given the results of the RAPIDO study above, and due to the COVID-19 pandemic increasing the need for hypofractionated radiotherapy, more patients are treated with short course radiation therapy. With this regimen, patients must be informed that radiation treatment toxicity usually happens after treatment is over, usually beginning approximately 1–2 weeks later. For this reason, a post-treatment check-up around that time is highly recommended, since patients often start chemotherapy a couple weeks after radiation, which can exacerbate gastrointestinal toxicities. Bentyl (dicycloverine), an anti-spasmodic medication can be helpful with symptoms of tenesmus, and the dose we would recommend is 20 mg QID. Proctofoam can also help with symptoms of radiation proctitis, although needs to be directly inserted into the anal canal which can be uncomfortable/difficult for patients. Anecdotally, some colleagues empirically prescribe dexamethasone for patients receiving short course radiotherapy for 2–3 weeks, at a dose of 4 mg BID, although that is not our institution practice. Between short course and long course chemoradiation, we counsel patients that acute toxicities from long course chemoradiation occur during treatment, are generally more predictable with smaller range between patients, and are easier to manage as patients are seen for on treatment visit. In contrast, there is a wider range of variation in toxicity from short course radiation with some patients experience very little toxicity and some with quite severe sub-acute toxicity as above. Fortunately, these side effects are mostly transient (however can be highly distressing). This difference in toxicity presentation may help patients choose between radiation regimens.

Management of chronic radiation enteritis is dependent upon symptoms. Usually, dietary modification is the first step, although this usually takes some trial and error. For symptoms of diarrhea and urgency, we instruct patients to avoid foods that are high in fiber. Even if the patient did not previously have lactose intolerance, we have found that asking patients to try limiting dairy indicate can be helpful. Probiotics have recently garnered high levels of interest due to emerging data on the role of the gut microbiome in colorectal cancer. A recent meta-analysis of trials suggested that probiotics may be effective in ameliorating radiation-induced diarrhea [6], so we sometimes suggest to patients to try probiotics (either in food or drink or pill form).

The mainstay of medical management includes anti-diarrheal agents and for patients with evidence of small intestinal bacterial overgrowth, antibiotics can be curative. Among anti-diarrheal agents, we generally use Imodium and loperamide.

For patients with severe refractory symptoms, we advise discussion of colostomy if they do not have one already. This can be upsetting to patients and in some ways make them feel like they have “failed” treatment, particularly if one of the goals of therapy was to avoid surgery and/or creation of a permanent colostomy. However, for those who have such severe gastrointestinal symptoms—particularly incontinence and urgency—that they are essentially homebound due to needing to be in proximity of a bathroom, having a colostomy can significantly improve quality of life.

In addition to the above, for symptoms of rectal pain, tenesmus, or bleeding, sucralfate enemas can be helpful. In a randomized trial of sulfasalazine plus prednisolone versus sucralfate enema, the response and toxicity profile of sucralfate enemas was superior [7], and another study showed that these responses tend to be durable [8]. For symptoms of obstructive due to radiation strictures, stool softeners may also be used.

Some patients experience persistent bleeding. Several endoscopic methods can be used to treat bleeding, the most common being argon plasma coagulation, which has been shown in several series to have efficacy rates upwards of 80% [9,10,11]. Other endoscopic methods including bipolar electrocoagulation with heating probe, radiofrequency ablation, band ligation, and formalin therapy. The success of these interventions is highly operator dependent, and there have been no large, randomized studies comparing the different methods. For patients with strictures, dilation with balloon can be highly effective. Finally, as above, colostomy creation should be discussed.

For all patients with chronic gastrointestinal symptoms, we recommend follow-up with a gastroenterologist and occasionally physical medicine and rehabilitation (PM&R), the latter particularly for musculoskeletal symptoms including stricture. These specialists can provide exercises for patients to perform on a regular basis at home and assess progress with specific metrics, rather than relying solely on symptomatic reporting.

A complete discussion of radiation-induced fertility and sexual toxicity is outside the scope of this piece; however, the topic is highly important, especially given the increasing number of young patients diagnosed with rectal cancer. Unfortunately, the ovaries are highly sensitive to radiotherapy, and all pre-operative and definitive doses used in rectal cancer will cause permanent infertility in women. While ovarian transposition is an option, internal radiation scatter cannot be eliminated and depending on placement of the ovaries, they may still not be spared sufficiently to prevent infertility. As such, for women interested in having future biologic children, we recommend egg harvesting prior to initiation of any therapy. This can be accomplished within several weeks. For men receiving radiotherapy, we quote the risk of infertility of approximately 20%. Therefore, sperm banking is recommended to maximize the probability of having biologic children. Conversely, for those who do not wish to have more children, contraception is advised during and after radiation therapy.

For females, the most common side sexual side effects of pelvic radiation are vaginal dryness and stricture which can lead to dyspareunia (pain with intercourse). For the former, we recommend the use of topical estrogen. Vaginal strictures/stenosis can be irreversible however they are preventable. We strongly advise all female patients to use a vaginal dilator starting 4–6 weeks after completion of pelvic radiotherapy. We advise use 3 times weekly, for 15–30 min, with the largest comfortable dilator size. Dilator use can also be supplanted with sexual intercourse. The most critical window for dilator usage to prevent strictures is about 3 months to 1 year after completion of radiotherapy.

For men, the dose of radiation used in rectal cancer is generally lower than nerve tolerance and thus is unlikely the cause of erectile dysfunction. However, rates of sexual dysfunction in men after rectal surgery are high because peripheral nerves controlling sexual function are frequently sacrificed during total mesorectal excision. In a study of 343 men who underwent surgery for rectal cancer, the incidence of sexual dysfunction was approximately 70% and close to 80% in those undergoing lateral lymph node dissection [12]. Age was a significant predictor of erectile dysfunction which was more common in older males.