Non‐surgical interventions for late rectal problems (proctopathy) of radiotherapy in people who have received radiotherapy to the pelvis New search for studies and content updated (no change to conclusions)

Abstract

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.

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

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.

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.

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

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. 

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.

Author(s)

Fleur T van de Wetering, Leen Verleye, H. Jervoise N Andreyev, Jane Maher, Joan Vlayen, Bradley R Pieters, Geertjan van Tienhoven, Rob JPM Scholten

Abstract

Non‐surgical interventions for late rectal consequences of radiotherapy in people who have received radical radiotherapy to the pelvis 

Background 

Radiotherapy is often used to treat cancer in the pelvic area. Several organs in the pelvis, such as the anus, rectum, bladder, prostate, gynaecological organs (womb, ovaries, cervix, and vagina), small bowel, and pelvic bones may be exposed to the effects of radiotherapy, which can lead to pelvic radiation disease. Symptoms from pelvic radiation disease may occur around the time of treatment (early effects) or over a period of time, often many years after treatment (late effects) due to long‐term changes secondary to scarring (fibrosis), narrowing (stenosis), and bleeding due to new blood vessel formation (telangiectasia). Damage to the rectum (radiation proctopathy) is the most often investigated late radiation effect to the pelvis, which affects a small but but still important group of people who undergo pelvic radiotherapy. The common symptoms are rectal urgency, rectal incontinence, pain, mucus discharge, and rectal bleeding.

The aim of the review 

The aim of this review was to assess the effect of non‐surgical treatments on late rectal damage.

Main Findings 

We found 16 (quasi) randomised controlled trials (RCTs) including 993 participants that assessed non‐surgical treatments for radiation proctopathy. Although some treatments look promising (including rectal sucralfate, adding metronidazole to an anti‐inflammatory regimen, and hyperbaric oxygen therapy), the quality of evidence was low to very low. Furthermore, outcomes important to people with cancer, including quality of life (QoL), and long‐term effects were often not addressed in these studies.

Conclusions 

Although some interventions for late radiation rectal damage are promising, the evidence was of low quality and we can draw no firm conclusions. We could not combine data from the studies to compare different treatments, since the trial designs and outcome measures differed. The episodic and variable nature of late radiation rectal damage requires larger RCTs to establish whether treatments are effective. Future studies should address the possibility of associated injury to other pelvic structures, collectively known as pelvic radiation disease. Ideally outcome measures should be standardised across studies and include QoL evaluations and other outcomes important to people with cancer .

Quality of the evidence 

The quality of the evidence for the majority of outcomes was low or very low, mainly due to the small size of most studies and study limitations.

Author(s)

Fleur T van de Wetering, Leen Verleye, H. Jervoise N Andreyev, Jane Maher, Joan Vlayen, Bradley R Pieters, Geertjan van Tienhoven, Rob JPM Scholten

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

One of the most commonly used treatments against rectal bleeding is argon plasma coagulation (APC). Though APC is very effective against rectal blood loss and considered standard, to our knowledge it had never been tested in a randomised fashion. APC works to reduce rectal blood loss but not other symptoms. The treatments tested in addition to APC showed no benefit. The significant results of formalin dab treatment (4%) versus sucralfate steroid retention enema and colonic irrigation plus ciprofloxacin and metronidazole versus formalin application (4%) are hampered by the fact that they were not compared to APC and may only be indicated in case of contraindications to APC. The same applies to the three studies investigating a broader spectrum of anorectal symptoms, one of which showed an advantage of adding metronidazole to mesalazine and betamethasone enema (only for the symptom rectal blood loss). The remaining four studies focused on the entire symptom complex that may be described as pelvic radiation disease. One of these (the largest) showed that specialistic care in the form of a gastroenterologist‐ or nurse‐led algorithm is better then a self help booklet. The remaining three studies showed a benefit from the investigated treatment, but two of these were very small. Only hyperbaric oxygen showed an advantage over placebo in a reasonably sized randomised study, hence this was the most convincing evidence.

Overall, we conclude for general practice that radiation proctopathy is more complex than rectal blood loss, which many studies focussed upon. The studies focusing only or mainly on rectal blood loss are hampered by the fact that the treatment considered standard for this condition was never investigated in a randomised manner. The broader radiation proctopathy and pelvic radiation disease likely require specialistic care, for instance in the form of a gastroenterologist‐led algorithm. The most convincing evidence for improvement of the symptom complex of radiation proctopathy was shown for hyperbaric oxygen therapy.

Implications for research 

The evidence for the effectiveness of non‐surgical interventions for late radiation proctopathy is limited and hampered by a lack of common standards. Although certain interventions look promising, single small studies (even if well conducted) provide limited evidence. Some commonly used treatments have not been investigated in RCTs. This review is furthermore hampered by the inability to compare the different studies.

Pelvic radiation disease is often not confined to one organ, and symptomatology is based on physiological disorders. Radiation proctopathy, which was the focus of this review, is but one aspect of pelvic radiation disease. The true incidence of the disease is not clear. Before setting up future trials, a widely used uniform definition of this disorder is warranted to serve as a basis. Secondly, there is an urgent need to clearly define the endpoints to investigate and to use a unified grading system by which these endpoints can be categorised, such as the CTCAE or the LENT‐SOMA for late radiation effects, to our knowledge the most widely used and well‐validated classification system of (late) toxicity symptoms, which however is not as sensitive as some other scales (Khalid 2006; Olopade 2005). Without such a system, it is unlikely that meaningful randomised studies can be designed. Future RCTs should also include major important patient‐reported outcome measures’, such as long‐term effects and quality of life evaluations.

Get full text at The Cochrane Library

Non‐surgical interventions for late rectal problems (proctopathy) of radiotherapy in people who have received radiotherapy to the pelvis New search for studies and content updated (no change to conclusions) is a sample topic from the Cochrane Abstracts.

To view other topics, please or .

Evidence Central is an integrated web and mobile solution that helps clinicians quickly answer etiology, diagnosis, treatment, and prognosis questions using the latest evidence-based research. .