Despite the growing recognition of the burden of OIC in cancer patients leading to the development of new drugs targeting the underlying cause, few specific clinical guidelines for the management of OIC have been published [11, 13, 20, 24]. The present Delphi consensus was intended to be a useful tool to provide practical recommendations based on the experience of different Spanish physicians experts on opioid use and OIC.
OIC is a frequent problem among patients with cancer, and often underdiagnosed [14], as the panellist agreed. To identify effectively cancer patients with OIC, symptoms had to be assessed regularly since they can be present at the time of opioid prescription and throughout the treatment. It is recommendable to use simple, not time consuming, measurable assessment tools in clinical practice, like the Bowel Function Index (BFI), in line with previous recommendations [12, 25, 26, 14]. However, the BFI only collect patient-reported outcomes but not objective symptoms. Therefore, a more comprehensive tool based on Rome IV criteria and definition of OIC need to be developed.
For a successful management of OIC, functional constipation should be identified and treated before opioid treatment is initiated to avoid further complications. Previous study, observed that 71% of patient with constipation prior to opioid treatment had experienced exacerbation of symptoms with opioids [27].
The panel agreed OIC need specific and targeted management due to the specific pathophysiological features. For that reason, the first step is to be aware that OIC can be present at any time during opioid treatment and therefore OIC treatment should remain throughout opioid use. Prophylaxis, as well as early treatment, was considered essential to avoid further adverse events and complications. However, experts observed that despite recommendations [28], many patients on opioid treatment do not receive laxative prophylactic treatment, possibly because prevention in clinical practice is often merely informative.
Regarding conventional OIC therapy, the panel considered that addressing life-style aspects is important due to the multifactorial origin of constipation in cancer patients. However, changing life-style only do not alleviate OIC symptoms. Similarly, many times laxatives have shown poor efficacy [16, 28, 10, 29]. New therapeutic alternatives take on special value in this patient group. The new agents not only target the underlying cause of the problem, but also provide solution where there was none, introducing a new paradigm in the OIC treatment scheme [12, 21, 25, 14].
Panel agreed management of OIC should be tailored based on individual patient needs. Based on clinical practice, osmotic laxatives were barely considered first therapeutic option for OIC in cancer patients. Osmotic laxatives have been strongly endorsed for their efficacy in improving stool frequency and consistency in patients with chronic constipation [12, 30]. Furthermore, for the treatment of functional constipation osmotic laxatives have been recommended for hard stools, whereas stimulant laxatives are recommended for soft stools [30, 31]. However, these recommendations address other causes of constipation but not the problem of OIC, and to date, there is no enough evidence which suggest that one laxative is better than others [12, 32]. Therefore, the experts concluded that although osmotic laxatives could be more frequently used, given the paucity of the evidence there are insufficient data to make a general recommendation of one laxative over the other for the treatment of OIC in cancer patients. Clinicians should select laxatives based on the individual patient symptoms, needs, and performance status [12, 30, 31].
Oral PAMORAs were considered good therapeutic option for the treatment of OIC in cancer patient. According to latest publications, PAMORAs have been recommended for OIC when laxatives results in incomplete relieve of symptoms [12, 21]. Successful management of OIC requires a complete individual clinical evaluation being critical to establish the cause of constipation. A recent European expert consensus about OIC management has suggested to start treatment with an opioid antagonist if constipation was considered to be secondary to opioid therapy [14].
Moreover, cancer patients often suffer with mix aetiology constipation, and a comprehensive management should be installed. In this study, panel recommended co-prescription of laxatives with PAMORA in patients experiencing multifactorial constipation. Yet appropriate therapeutic scheme: laxative dose, laxative type, etc. need to be validated and requires further investigation. Definition of treatment failure is crucial for the success of OIC management, however it has been defined variably in the literature [12, 21, 26, 30]. Nonetheless, the panel recommended that treatment efficacy should be assessed as soon as possible and preferable within a week.
Finally, the panel evaluated the burden of OIC in the quality of life of cancer patients. According with previous data [9, 33, 10], panel agreed OIC negatively impact on the quality of life of cancer patients. Poorly controlled symptoms can result in increasing emergency department visits, unplanned hospitalizations, uncontrolled pain, delays in treatment, and lack of adherence and persistence with an effective treatment course. Patient perception of the burden of the problem, quality of life, and treatment has also a great impact on the success of the treatment and symptoms relief, therefore it should not be undervalued. Many clinicians are aware that improving cancer outcomes requires a focus not only on the main disease but also on patient illness experience and symptoms and their impact on the quality of life and their families. Systematic monitoring of patient-reported outcomes, including minor symptoms and patient experience, is now an essential component of cancer care [34-36].
The limitations of this study are similar to those of others with a comparable design. The promotor has not been involved in the development of the study, so a possible influence in the consensus has been minimized. One of the main strengths of this study is the participation of different kinds of physicians experts in OIC with high clinical experience. Far from being a disadvantage, this approach enriched and strengthened the consensus, since each item is evaluated from different points of view. In addition, the high degree of consensus reached give the study great validity of its results.