Proctitis

Definition

Radiation proctitis is a term used to describe radiation-induced injury to the rectal mucosa following radiation therapy to the pelvic area.^r Depending on the time of onset, and to a lesser extent the clinical features and histology, radiation proctitis is defined as being either acute or chronic.

Pathophysiology

The rectum is at risk of injury during pelvic irradiation because of its proximity to target organs.^r

Acute radiation proctitis is caused by direct radiation injury to the rectal mucosa, which results in inflammation with oedema, ulceration and shedding of the mucosa.^r

Chronic radiation proctitis is related to late effects of radiation damage. Injury to small blood vessels causes progressive ischaemic changes and atrophy of the rectal mucosa. This is followed by ulceration, fibrosis and telangiectasia development. In severe cases, strictures and fistulae may result.

Incidence/prevalence

Exact figures vary, but it is widely accepted that most patients receiving pelvic irradiation will develop some degree of acute radiation proctitis and approximately 1-5% of patients will experience chronic radiation proctitis.^r However, it has been suggested that a much higher percentage of patients receiving pelvic radiation will have a permanent change to their bowel habits and for a significant number this may impair their quality of life.^r The condition is probably underreported, as patients may be reluctant to report symptoms due to embarrassment or a belief that nothing can be done about them.^rrr

Onset/duration

Acute radiation proctitis presents during or shortly after radiation therapy. It lasts for less than 6 months after treatment and in most cases resolves within a few weeks of finishing therapy.

Chronic radiation proctitis may follow on from acute radiation proctitis or occur after a symptom-free period (generally more than 90 days after completion of treatment).^rrr The median time of presentation is around 8-12 months after treatment but can also present many years after radiation therapy.^r There have been reports of spontaneous improvement or resolution of symptoms in some patients over time however large-scale studies are required to confirm this.^rrr

Risk factors

Radiation proctitis occurs most commonly in patients receiving treatment for prostate, cervical, anal and rectal cancers but can also occur after radiation therapy to the pelvic area for other tumour types.^r 

Treatment-related factors include:

• volume of rectum irradiated
• higher doses to rectum
• external beam radiation.

Patient-related factors include:^rrrrr

• tumour stage
• genotypic susceptibility to radiation toxicity
• patient’s general condition e.g. age, malnutrition
• previous abdominal surgery
• smoking
• concurrent treatments, particularly chemotherapy
• co-morbidities, including diabetes, vascular disease, inflammatory bowel disease and HIV.

There is also evidence that the occurrence and/or severity of acute radiation proctitis may be predictive of the development of chronic radiation proctitis.^rrr This correlation may have implications for future preventative strategies and interventions.^r

Symptoms

Radiation proctitis results in a range of bowel symptoms which can significantly impair patient quality of life.

Symptoms of acute radiation proctitis include:

• diarrhoea (common)
• faecal urgency
• tenesmus (the feeling of needing to pass stools even when the bowel is empty)
• mucous discharge
• abdominal/pelvic pain or cramping
• bleeding (uncommon).

Symptoms of chronic radiation proctitis include:

• diarrhoea
• constipation
• faecal urgency
• faecal incontinence
• tenesmus (the feeling of needing to pass stools even when the bowel is empty)
• anorectal dysfunction
• abdominal/pelvic pain or cramping
• mucous discharge
• rectal bleeding (common) – resulting in anaemia. Bleeding can be caused by rectal strictures, ulcerations or fistulas.

Investigations and diagnosis

Acute radiation proctitis is diagnosed based on symptoms and specific investigations are not generally required.^r

Chronic radiation proctitis should be investigated more extensively. The key requirements are to exclude other possible causes of the patient’s symptoms and to identify management strategies. Referral to a gastroenterologist for comprehensive assessment may be appropriate in some cases.^r

Not all gastrointestinal symptoms reported by patients who have had pelvic irradiation are necessarily caused by radiation.^r In addition, even when radiation-induced rectal injury exists, more proximal gastrointestinal injury may also affect bowel function and contribute to patient symptoms.^r 

Patient assessment may include:^rrrrr

• detailed history
• blood tests, e.g., haematological and biochemical profiles, inflammatory and tumour markers
• stool samples to exclude infectious causes
• endoscopy (possibly with biopsy)*
• imaging (not routinely used), e.g. MRI, CT, barium enema.

* Endoscopy can be useful to confirm the diagnosis and exclude other possible causes. However, it is recommended that biopsy is used with caution because of the risk of fistula development.^r

Grading

There is not a single universally accepted grading system for radiation proctitis.^rr

The National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) is a widely used measure, although this is not specific to radiation-induced injury. It provides grading for proctitis, as well as for individual symptoms including diarrhoea, rectal haemorrhage and faecal incontinence as seen in Table 1.^r

Common Terminology Criteria for Adverse Events opens in a new tab or window (CTCAE) v5.0, 27 November, 2017

The European Organisation for the Research and Treatment of Cancer (EORTC) radiation proctitis questionnaire opens in a new tab or window is a validated tool to measure quality of life in patients experiencing radiation proctitis. ^r

Prevention

The primary approach to the prevention of radiation proctitis is to minimise the radiation dose to the rectum through highly conformal treatment using image-guided radiation therapy (IGRT) and intensity-modulated radiation therapy(IMRT) and/or volumetric arc therapy (VMAT). Other physical techniques have been used to minimise the dose of radiation reaching normal tissues e.g., transperineal injection of a temporary rectal spacer gel between the prostate and rectum.^r Some patients may receive specific instructions for bowel and bladder preparation before radiation treatment to ensure consistent positioning of these organs during therapy and to achieve the planned radiation dose distribution. Written information may be useful to achieve this consistency, see eviQ patient information sheet Preparing your bladder and bowel for pelvic radiation therapy.

Attempts to use adjunctive medical therapy to prevent radiation proctitis have shown benefit in small trials, reducing symptoms of both acute and chronic radiation proctitis.^rr The Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines for the management of mucositis secondary to cancer therapy opens in a new tab or window recommend intravenous amifostine for preventing radiation proctitis.^r

Gastrointestinal symptoms

Several interventions have been trialled in patients receiving pelvic irradiation to either prevent or control gastrointestinal symptoms which can be caused by radiation proctitis or from more proximal bowel damage. The MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy opens in a new tab or window provide recommendations and suggestions for the use of medications to manage diarrhoea from radiation-induced proctitis.^r Dietary interventions that have been investigated include lactose restriction, fat restriction or modification and fibre supplementation. Although no specific treatments have been recommended, there is some evidence that dietary modification may reduce acute symptoms of diarrhoea in patients receiving pelvic irradiation.^r For further management information see eviQ clinical resource Treatment induced diarrhoea.

Treatment

There are no comprehensive management guidelines and only limited evidence for the treatment of radiation proctitis.

Acute proctitis

Patients with severe symptoms of acute radiation proctitis may need to have their radiation therapy suspended for a short period.^r Otherwise, treatment is of a supportive nature including:

• maintaining adequate hydration
• dietary changes
• antidiarrhoeal medication as required
• analgesics if pain is a problem
• antispasmodics for tenesmus
• topical analgesia for anal soreness
• oral/rectal steroids and/or butyrate enemas may be considered.

Chronic proctitis

Chronic radiation proctitis can present with a range of symptoms and these will determine the choice of management strategy. The level of intervention required will depend on the severity of symptoms and the risk-benefit profile of available treatment options. Referral to a gastrointestinal specialist to guide treatment may be appropriate.

Because of uncertainty about the natural history of chronic radiation proctitis, the limited evidence for many therapies, and the risk of adverse effects, a conservative management approach is often advocated.^rrr This would include supportive measures similar to those used in acute proctitis. In addition, patients with rectal bleeding who are taking blood thinning medications (e.g. aspirin or warfarin) should have their need for these medications reviewed.^r Consideration should also be given to other factors which may be contributing to symptoms including more proximal gastrointestinal damage producing gastrointestinal hurry.^r Treatment of established radiation proctitis is generally classified as being medical, interventional or surgical, but the evidence for many therapies is limited and more large-scale, prospective trials are required to evaluate their benefit.^r

Medical treatments

A range of medical treatments have been used to manage radiation proctitis. These are mainly the same supporting treatments used in acute radiation proctitis to manage the symptoms. 

Treatment options for chronic radiation-induced proctitis with rectal bleeding include sucralfate enemas^rr and formalin^r. Systemic sucralfate, administered orally, is not recommended in this setting.^r

The use of a structured clinical algorithm with targeted management may also improve radiation therapy-induced gastrointestinal symptoms.^r Many authors point out that large, prospective, randomised, controlled trials are needed to critically evaluate the available options.^rrr For further management information see eviQ clinical resource Treatment induced diarrhoea.

Interventional treatments or surgery

When conservative treatments for chronic radiation proctitis have been unsuccessful, interventional treatments such as endoscopic argon plasma coagulation (AOC), hyperbaric oxygen, or surgery may be appropriate treatment options.^rr These patients should be referred to a gastrointestinal specialist in conjunction with the treating radiation oncologist.

Educate the patient about:

• the likelihood of developing acute and/or chronic radiation-induced proctitis prior to commencement of treatment.
• reporting immediately the development of symptoms during and after treatment.
• self-care strategies to manage symptoms including dietary changes, fluid intake to maintain hydration.
• when to start and how to take analgesic, anti-diarrhoeal and antispasmodic medication. 
• informing the treatment team of any planned changes to diet or medication.

Provide written material, e.g., eviQ patient information sheet diarrhoea during cancer treatment.

For patients with chronic radiation-induced proctitis, relevant management options should be discussed including referral to a gastrointestinal specialist.

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