Systematic review of clinical practice guidelines for colorectal and anal cancer: the extent of recommendations for managing long-term symptoms and functional impairments

Colon and rectal cancer combined are the third most commonly diagnosed cancer worldwide [1]. In 2018, 1,849,518 new cases of colon or rectal cancer were diagnosed, with an additional 48,541 anal cancers diagnosed [2]. The highest incidence rates are in developed countries, such as Australia with 16,171 newly diagnosed colorectal cancer patients and 470 anal cancer patients in 2018 [3]. Improvements in screening and treatment for bowel, colon, and anal cancer, referred to hereafter as colorectal cancer (CRC), have contributed to a growing population of cancer survivors with unmet needs, long-term symptoms, and functioning impairments after treatment that can negatively impact on health-related quality of life (HRQL) [4, 5].

Multiple long-term symptoms can be experienced after treatment for CRC. For bowel symptoms, these include rectal bleeding, diarrhea, fecal frequency, incontinence and urgency, and rectal tenesmus (feeling of incomplete defecation) [6]. Other common symptoms are chemotherapy-induced neuropathy, insomnia, fatigue, cognitive dysfunction, issues with body image, psychological distress, [7, 8], and sexual dysfunction [5]. All long-term symptoms contribute to increased symptom burden, in terms of both severity and frequency, which in turn is associated with decreased HRQL [9]. In order to decrease symptom burden and improve HRQL, evidence-based interventions should be used to manage long-term symptoms and functioning impairments. Since clinicians are often unaware of interventions designed to detect and manage symptoms [6], this systematic review aimed to investigate the extent to which clinical practice guidelines for CRC provide recommendations for managing long-term symptoms and functioning impairments following treatment for CRC.

Our systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance [10]. The following 4 electronic databases were searched using the OVID web gateway: MEDLINE, EMbase, PsycINFO, and CINAHL from inception to 26th of July 2019. The search strategy included terms for colorectal cancer and clinical practice guidelines. Details of the search strategy are reported in Appendix 1. To supplement this, reference lists of studies identified were used to find other relevant guidelines, and 33 international cancer societies and guideline organization websites were searched for additional guidelines, consensus statements, or best practice recommendations.

The searches retrieved 545 papers of which 20 were potentially eligible for inclusion. An additional 31 publications were retrieved through searches of international websites (Fig. 1). Fifty-one guidelines for CRC were identified (Appendix Table 3). Major international organizations that published these include the National Comprehensive Cancer Network (NCCN), American Society for Clinical Oncology (ASCO), and the European guidelines of the European Society for Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO), and European Society of Radiotherapy and Oncology (ESTRO). We found nine guidelines specific to colon cancer, nine for rectal cancer, and five for anal cancer, and twenty-eight guidelines providing recommendations for both colon and rectal cancer.

If information on surveillance was included in the guidelines, it emphasized recurrence detection during follow-up. Only 13 of the 51 guidelines (25.4%) met the eligibility criterion of containing information about how to manage or treat long-term symptoms and functioning impairments after treatment (Table 1).

The main focus of survivorship care in the guidelines is on detection of early recurrence, the timing of follow-up, and which diagnostic tools to use. Much less attention is paid to long-term symptoms and functioning impairment, or to the interventions recommended to manage and alleviate these issues to reduce patients’ symptom burden and improve HRQL. This is a major gap that needs to be filled as previous research demonstrates a link between HRQL and survival. In a large study of 1074 CRC patients, depressive symptoms significantly increased mortality risk in the first 2 years after diagnosis (hazard rate, 2.55, p = 0.001) with a hazard rate of 1.88 (p < 0.01) up to 10 years after diagnosis [24]. During the last few decades, more attention is being paid to developing interventions for late symptoms after cancer treatment. For example, Andreyev et al. reported that a gastroenterologist- or nurse-led algorithm-based treatment resulted in a decrease of bowel symptoms compared with a self-help booklet [25]. Also, interventions are emerging for sexual dysfunction after pelvic radiotherapy, such as mindfulness and cognitive behavioral therapy, couple therapy, scheduled intimacy, vaginal dilator therapy and moisturizers, hormone replacement, and phosphodiesterase type 5 inhibitors [26]. Research is needed to further assess interventions for long-term symptoms and functioning impairments. Moreover, guidelines recommend screening for distress and symptoms, but do not state if patient-reported outcomes could or should be used for routine screening. A number of trials have shown benefit of using patient-reported outcomes for routinely screening during treatment [27, 28]; their potential benefit in long-term follow-up of CRC should be investigated.

Several guidelines refer to generic survivorship guidelines. While these were excluded from our review, we note that the 2019 NCCN survivorship guideline contains information about long-term symptoms and treatment of cardiotoxicity, depression, anxiety, cognitive function, fatigue, lymphoedema, hormone problems, pain, sexual function, and sleep, independent of the location of the primary cancer. Unfortunately, interventions for gastrointestinal problems are not included [29]. NCCN regularly updates all guidelines. The NCCN guidelines for colon and rectal cancer met our inclusion criteria regarding information on long-term adverse effects after treatment and possible interventions, but in an older version (the NCCN CRC guideline), such information was not provided. The inclusion of this information in the updated guideline suggests rising international awareness for late effects and HRQL.

This systematic review highlights the limited guidance available on how to manage long-term symptoms and functioning impairments in CRC survivors. This knowledge gap has implications for both clinicians, patients, and their informal caregivers. A previous review showed that many CRC survivors find ways to self-manage their symptoms through trial and error rather than seek professional help [30]. Self-help strategies are often not evidence-based, so it may not be effective and perhaps even detrimental, worsening symptoms or impairment. It is not clear why survivors choose to self-manage, but the absence of recommendations for clinicians in clinical practice guidelines may at least in part be a contributing factor. Moreover, none of the guidelines addressed the need to support informal caregivers in managing symptoms. As mentioned above, interventions have been developed to manage several symptoms and functions caused by treatment for cancer, yet expert opinions are often used to inform clinical practice guidelines rather than evidence from clinical effectiveness trials. It is unclear whether the use of expert opinion is due to limited effectiveness evidence. Future research should focus on synthesizing all available evidence on supportive care interventions and management strategies, and guidelines need to be updated periodically to incorporate emerging evidence. Another recommendation, also stated in a few guidelines, is the use of survivorship clinics. Literature shows that patients are highly satisfied with the services of such a clinic, mainly due to the multidisciplinary approach, the time taken to address the symptoms, and the referrals to appropriate supporting programs [31].

Strengths of this review are the inclusion of international guidelines, a thorough search of both electronic databases and websites for 33 cancer societies, and guideline quality assessment against the criteria of the AGREE II tool. Two limitations of our review were the inclusion of only guidelines available in English, and with our search process, we could not accurately count the number of non-English guidelines excluded. Some non-English guidelines that we did not have resources to review may provide recommendations for long-term symptoms or functions. For example, the Dutch national guideline for CRC (which we are aware of as LW is a Dutch clinician) provides risk factors for fecal incontinence, recommends the use of diagnostic tools to evaluate long-term symptoms, and provides interventions for managing specific problems such as fecal incontinence with bulk-forming agents or loperamide to decrease fecal frequency [32]. However, despite excluding non-English guidelines, we expect that they would be informed by the same international evidence that informed guidelines published in English.

In conclusion, the majority of guidelines for CRC reviewed did not provide recommendations for management of long-term symptoms and functioning impairment following treatment for CRC. Their recommendations primarily focus on detection of early recurrence, the timing of follow-up, which diagnostic tools to use, and on the importance of a healthy diet and weight, and active lifestyle after treatment. Few recommendations are available for how to reduce or manage symptom burden and improve HRQL. This may be due to lack of evidence about effectiveness of potential management strategies. There is need for clear evidence-based recommendations for managing long-term symptoms and functioning impairments to assist health professionals in supporting CRC survivors and to ameliorate suffering due to persistent symptoms and functioning impairments that often go unmanaged.