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. 2016 Apr 25;4(4):CD003455.
doi: 10.1002/14651858.CD003455.pub2.

Non-surgical interventions for late rectal problems (proctopathy) of radiotherapy in people who have received radiotherapy to the pelvis

Fleur T van de Wetering  1 , Leen Verleye, H Jervoise N Andreyev, Jane Maher, Joan Vlayen, Bradley R Pieters, Geertjan van Tienhoven, Rob J P M Scholten
Affiliations

Non-surgical interventions for late rectal problems (proctopathy) of radiotherapy in people who have received radiotherapy to the pelvis

Fleur T van de Wetering et al. Cochrane Database Syst Rev. .

Abstract

Background: This is an update of a Cochrane review first published in 2002, and previously updated in 2007. Late radiation rectal problems (proctopathy) include bleeding, pain, faecal urgency, and incontinence and may develop after pelvic radiotherapy treatment for cancer.

Objectives: To assess the effectiveness and safety of non-surgical interventions for managing late radiation proctopathy.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 11, 2015); MEDLINE (Ovid); EMBASE (Ovid); CANCERCD; Science Citation Index; and CINAHL from inception to November 2015.

Selection criteria: We included randomised controlled trials (RCTs) comparing non-surgical interventions for the management of late radiation proctopathy in people with cancer who have undergone pelvic radiotherapy for cancer. Primary outcomes considered were: episodes of bowel activity, bleeding, pain, tenesmus, urgency, and sphincter dysfunction.

Data collection and analysis: Study selection, 'Risk of bias' assessment, and data extraction were performed in duplicate, and any disagreements were resolved by involving a third review author.

Main results: We identified 1221 unique references and 16 studies including 993 participants that met our inclusion criteria. One study found through the last update was moved to the 'Studies awaiting classification' section. We did not pool outcomes for a meta-analysis due to variation in study characteristics and endpoints across included studies.Since radiation proctopathy is a condition with various symptoms or combinations of symptoms, the studies were heterogeneous in their intended effect. Some studies investigated treatments targeted at bleeding only (group 1), some investigated treatments targeted at a combination of anorectal symptoms, but not a single treatment (group 2). The third group focused on the treatment of the collection of symptoms referred to as pelvic radiation disease. In order to enable some comparison of this heterogeneous collection of studies, we describe the effects in these three groups separately.Nine studies assessed treatments for rectal bleeding and were unclear or at high risk of bias. The only treatments that made a significant difference on primary outcomes were argon plasma coagulation (APC) followed by oral sucralfate versus APC with placebo (endoscopic score 6 to 9 in favour of APC with placebo, risk ratio (RR) 2.26, 95% confidence interval (CI) 1.12 to 4.55; 1 study, 122 participants, low- to moderate-quality evidence); formalin dab treatment (4%) versus sucralfate steroid retention enema (symptom score after treatment graded by the Radiation Proctopathy System Assessments Scale (RPSAS) and sigmoidoscopic score in favour of formalin (P = 0.001, effect not quantified, 1 study, 102 participants, very low- to low-quality evidence), and colonic irrigation plus ciprofloxacin and metronidazole versus formalin application (4%) (bleeding (P = 0.007, effect not quantified), urgency (P = 0.0004, effect not quantified), and diarrhoea (P = 0.007, effect not quantified) in favour of colonic irrigation (1 study, 50 participants, low-quality evidence).Three studies, of unclear and high risk of bias, assessed treatments targeted at something very localised but not a single pathology. We identified no significant differences on our primary outcomes. We graded all studies as very low-quality evidence due to unclear risk of bias and very serious imprecision.Four studies, of unclear and high risk of bias, assessed treatments targeted at more than one symptom yet confined to the anorectal region. Studies that demonstrated an effect on symptoms included: gastroenterologist-led algorithm-based treatment versus usual care (detailed self help booklet) (significant difference in favour of gastroenterologist-led algorithm-based treatment on change in Inflammatory Bowel Disease Questionnaire-Bowel (IBDQ-B) score at six months, mean difference (MD) 5.47, 95% CI 1.14 to 9.81) and nurse-led algorithm-based treatment versus usual care (significant difference in favour of the nurse-led algorithm-based treatment on change in IBDQ-B score at six months, MD 4.12, 95% CI 0.04 to 8.19) (1 study, 218 participants, low-quality evidence); hyperbaric oxygen therapy (at 2.0 atmospheres absolute) versus placebo (improvement of Subjective, Objective, Management, Analytic - Late Effects of Normal Tissue (SOMA-LENT) score in favour of hyperbaric oxygen therapy (HBOT), P = 0.0019) (1 study, 150 participants, moderate-quality evidence, retinol palmitate versus placebo (improvement in RPSAS in favour of retinol palmitate, P = 0.01) (1 study, 19 participants, low-quality evidence) and integrated Chinese traditional plus Western medicine versus Western medicine (grade 0 to 1 radio-proctopathy after treatment in favour of integrated Chinese traditional medicine, RR 2.55, 95% CI 1.30 to 5.02) (1 study, 58 participants, low-quality evidence).The level of evidence for the majority of outcomes was downgraded using GRADE to low or very low, mainly due to imprecision and study limitations.

Authors' conclusions: Although some interventions for late radiation proctopathy look promising (including rectal sucralfate, metronidazole added to an anti-inflammatory regimen, and hyperbaric oxygen therapy), single small studies provide limited evidence. Furthermore, outcomes important to people with cancer, including quality of life (QoL) and long-term effects, were not well recorded. The episodic and variable nature of late radiation proctopathy requires large multi-centre placebo-controlled trials (RCTs) to establish whether treatments are effective. Future studies should address the possibility of associated injury to other gastro-intestinal, urinary, or sexual organs, known as pelvic radiation disease. The interventions, as well as the outcome parameters, should be broader and include those important to people with cancer, such as QoL evaluations.

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Conflict of interest statement

Fleur T van de Wetering: nothing to declare Leen Verleye: nothing to declare H. Jervoise N Andreyev: first author of one of the included studies Jane Maher: nothing to declare Joan Vlayen: nothing to declare Bradley R Pieters: nothing to declare Geertjan van Tienhoven: nothing to declare Rob JPM Scholten: nothing to declare

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 Short chain fatty acid (SCFA) enemas versus placebo, Outcome 1 Mean reduction of endoscopic score after treatment.
1.2
1.2. Analysis
Comparison 1 Short chain fatty acid (SCFA) enemas versus placebo, Outcome 2 Mean number of days of rectal bleeding after treatment.
1.3
1.3. Analysis
Comparison 1 Short chain fatty acid (SCFA) enemas versus placebo, Outcome 3 Mean haemoglobin levels at the end of treatment period (5 weeks).
2.1
2.1. Analysis
Comparison 2 Endoscopic argon plasma coagulation (APC) plus oral sucralfate versus APC plus placebo, Outcome 1 Endoscopy scores Gilinsky scale grade 6‐9 at 8 weeks.
2.2
2.2. Analysis
Comparison 2 Endoscopic argon plasma coagulation (APC) plus oral sucralfate versus APC plus placebo, Outcome 2 Endoscopy scores Gilinsky scale grade 6‐9 at 16 weeks.
2.3
2.3. Analysis
Comparison 2 Endoscopic argon plasma coagulation (APC) plus oral sucralfate versus APC plus placebo, Outcome 3 Number of participants with complications.
3.1
3.1. Analysis
Comparison 3 Endoscopic bipolar electrocoagulation versus heater probe, Outcome 1 Severe bleeding episodes.
3.2
3.2. Analysis
Comparison 3 Endoscopic bipolar electrocoagulation versus heater probe, Outcome 2 Mean number of severe bleeds after first year.
3.3
3.3. Analysis
Comparison 3 Endoscopic bipolar electrocoagulation versus heater probe, Outcome 3 Mean haematocrit after first year.
3.4
3.4. Analysis
Comparison 3 Endoscopic bipolar electrocoagulation versus heater probe, Outcome 4 Mean units of blood transfused after first year.
4.1
4.1. Analysis
Comparison 4 APC versus bipolar electrocoagulation, Outcome 1 Eradication of all telangiectasias.
4.2
4.2. Analysis
Comparison 4 APC versus bipolar electrocoagulation, Outcome 2 Complications ‐ Minor.
4.3
4.3. Analysis
Comparison 4 APC versus bipolar electrocoagulation, Outcome 3 Complications ‐ Major.
4.4
4.4. Analysis
Comparison 4 APC versus bipolar electrocoagulation, Outcome 4 Relapse.
5.1
5.1. Analysis
Comparison 5 Hydrocortisone versus betamethasone, Outcome 1 Improvement of endoscopic appearance.
5.2
5.2. Analysis
Comparison 5 Hydrocortisone versus betamethasone, Outcome 2 Reduction of rectal bleeding.
5.3
5.3. Analysis
Comparison 5 Hydrocortisone versus betamethasone, Outcome 3 Poor tolerance of enema.
6.1
6.1. Analysis
Comparison 6 Standard treatment plus oral pentoxifylline versus standard treatment, Outcome 1 Cessation of rectal bleeding.
7.1
7.1. Analysis
Comparison 7 Oral sulfasalazine plus rectal steroids versus oral placebo plus rectal sucralfate, Outcome 1 Clinical improvement.
7.2
7.2. Analysis
Comparison 7 Oral sulfasalazine plus rectal steroids versus oral placebo plus rectal sucralfate, Outcome 2 Endoscopic improvement.
8.1
8.1. Analysis
Comparison 8 Metronidazole in addition to mesalazine and betamethasone versus no metronidazole, Outcome 1 Rectal bleeding score < 2 after 1 year.
8.2
8.2. Analysis
Comparison 8 Metronidazole in addition to mesalazine and betamethasone versus no metronidazole, Outcome 2 Diarrhoea score < 2 after 1 year.
8.3
8.3. Analysis
Comparison 8 Metronidazole in addition to mesalazine and betamethasone versus no metronidazole, Outcome 3 No rectal erythema after 1 year.
8.4
8.4. Analysis
Comparison 8 Metronidazole in addition to mesalazine and betamethasone versus no metronidazole, Outcome 4 No rectal ulceration after 1 year.
9.1
9.1. Analysis
Comparison 9 Hyperbaric oxygen therapy versus placebo, Outcome 1 Clinical evaluation ‐ healed or improved.
10.1
10.1. Analysis
Comparison 10 Retinol palmitate versus placebo, Outcome 1 Response to treatment.
11.1
11.1. Analysis
Comparison 11 Algorithm‐based management, Outcome 1 Bowel subset score (IBDQ‐B) at 6 months (higher score indicates better).
11.2
11.2. Analysis
Comparison 11 Algorithm‐based management, Outcome 2 Change in rectal SOMA‐LENT at 6 months.
11.3
11.3. Analysis
Comparison 11 Algorithm‐based management, Outcome 3 Change in small intestine SOMA‐LENT at 6 months.
11.4
11.4. Analysis
Comparison 11 Algorithm‐based management, Outcome 4 SF12: change in physical component score at 6 months.
11.5
11.5. Analysis
Comparison 11 Algorithm‐based management, Outcome 5 SF12: change in mental component score at 6 months.
12.1
12.1. Analysis
Comparison 12 Integrated Chinese traditional medicine plus Western medicine versus Western medicine, Outcome 1 Grade of radioproctitis after treatment Grade I.
12.2
12.2. Analysis
Comparison 12 Integrated Chinese traditional medicine plus Western medicine versus Western medicine, Outcome 2 Cured ‐ better after 37 days.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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References to studies awaiting assessment

Chen 2002 {published data only}
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References to ongoing studies

Botten 2011a {published data only}
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