Pain is a significant problem in patients with cancer. Half of patients undergoing active therapy have pain, more than one-third of cancer patients have pain after curative-intent therapy, and up to two-thirds of patients with advanced or metastatic cancer have pain (Everdingen et al. 2016). Chronic pain is also present in about half of the cancer survivors (Marnangeli et al. 2022).

The etiology of pain in patients with cancer is multifactorial and may be related not only to the underlying cancer but also to comorbidities, cancer therapies, or the psychosocial factors that often accompany chronic or terminal illness.

Breakthrough cancer pain(BTcP), a transient exacerbation of pain that occurs within the context of stable and adequately controlled background pain, is part of this complex problem.(Portenoy et al. 1999)

There is no universally accepted definition to describe breakthrough cancer pain. Additionally, there is disagreement as to what constitutes breakthrough cancer pain (Zeppetella 2009). More recent definitions do not include regular opioid medication or background pain as prerequisites for BTcP(Løhre et al. 2020, Mercadante et al. 2016).

BTP is highly variable, (Davies et al. 2013) with a prevalence ranging from 40% to 80%, (Deandrea et al. 2014) but prevalence rates of 90% have been reported (Zeppetella et al. 2000) and may result from the disease itself, disability caused by cancer, anticancer treatment or other factors. It usually has a rapid onset - that is, a time to peak severity of 5–30 min, but with a wide range extending to1 hour (Caraceni et al. 2004). Its duration is often shortlasting and<60 min but may last for >3 hours.

The differences reported are probably because of different settings and meanings attributed to the definition of breakthrough pain. In an international survey of cancer pain characteristics and syndromes, large differences in the diagnosis of breakthrough pain by clinicians of different countries have been found, suggesting that this phenomenon is diagnosed differently in various countries (Caraceni et al 1999). These controversial aspects, both semantic and clinical, were discussed in a consensus meeting of an expert working group from the Research Network of the European Association for Palliative Care during the 2nd International and Hellenic Conference on Pain Relief and Palliative Care (PA.RH.SYA) held in Athens in March 1999. (Mercadante et al. 2002)

BTcP may be nociceptive, neuropathic or a mixture of both. (Vadalouca et al. 2012)

Cancer BTP is often severe and can greatly interfere with all aspects of daily living.

One of the biggest problems with breakthrough cancer pain is its underassessment, and it is therefore underrecognized and undertreated. Pain assessment usually consists of questions about pain location, intensity, quality, and temporal factors. However, a lack of standardized assessment approaches exists for breakthrough cancer pain (Brant and Stringer 2018).

Clinical Practice Guidelines (CPGs) are statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options. Recommendations are the core components of CPGs and should be presented as clear, specific and actionable statements.

Several Clinical Practice Guidelines (CPGs ), consensus statements, and recommendations currently exist for the diagnosis and management of breakthrough cancer pain (BTcP).

Generic Cancer Pain Guidelines providing recommendations about the management of BTcP, have been developed by: the European Association of Palliative Care (Caraceni et al. 2012) European Society for Medical Oncology (Ripamonti et al. 2012), the Cancer Council Australia (Cancer Guidelines Wiki), the Japanese Society Palliative Medicine (Yamaguchi et al. 2013), the Ministry of Health and Welfare and National Cancer Center South Korea, the National Comprehensive Cancer Network (2016).

Specific BTcP Guidelines were also generated by: the Association for Palliative Medicine of Great Britain and Ireland (Davies et al. 2009), the EAPC (Mercadante et al. 2002), the European Oncology Nursing Society (Wengström et al. 2014), the Sociedad Espanola del Dolor (Escobar Álvarez et al. 2013), an international pharmaceutical company-sponsored experts team in BTcP (Caraceni et al. 2013), the German Pain Society, the Italian Oncologic Pain Survey expert group (Mercadante et al. 2016), a meeting that produced the Canadian recommendations (Daeninck et al. 2016), and an interdisciplinary group of Spanish pain experts (López Alarcón et al. 2019).

French guidelines also discuss the use of the so-called rapid-onset opioids (ROOs) for BTcP( Poulain et al. 2012).

A recent systematic review of the above specific BTcP and international generic cancer pain guidelines concluded that current guidelines agree on many aspects of the management of BTcP. However, the evidence to support current guidelines remains low grade, and so more research is needed in this area of care. Moreover, there needs to be an international consensus on the definition and diagnosis criteria of BTcP.(Davies et al. 2018)

Also, this year a quality appraisal of CPGs has been performed for the diagnosis and management of BTcP using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. Scaled domain scores were generated and the threshold used for satisfactory quality was >60%. Additionally, intraclass correlation coefficients (ICC) were calculated to determine level of agreement between reviewers.

Eleven guidelines were selected for final evaluation. Only one guideline was classified of ‘average’ quality while the rest were classified as ‘low’ quality. The ‘Editorial Independence’ (70.46 ± 35.7) and ‘Scope and Purpose’ (64.78 ± 12.5) domains received the highest mean scores, while the ‘Applicability’ (32.58 ± 13.5) and ‘Rigor of Development’ (35.04 ± 9.0) domains received the lowest mean scores. ICC statistical analysis showed high magnitude of agreement between reviewers with a range of (0.790–0.988).

Reflecting upon this quality appraisal, it is evident that the quality and methodologic rigor of BTcP guidelines can be improved upon in the future. These findings also elucidate the existing variability/discrepancies among guidelines in diagnostic criteria and management of BTcP( Suresh et al. 2022).

Conclusion A comprehensive pain management approach that addresses the various presentations of pain in patients with cancer is required, including appropriate management of breakthrough pain (Caraceni et al 2013). Because pain is heterogeneous, the best management of an individual’s pain, including breakthrough pain in cancer, requires a thorough assessment to tailor the treatment strategies. The developed guidelines support this approach and recommend treating breakthrough pain using rapid- or short-acting opioids with pharmacodynamics that mirror the rapid onset and short duration of the presenting pain. This approach should be part of a comprehensive strategy to treat pain within the context of the primary disease trajectory, offering continuity of care and access to specialized Pain therapy and Palliative care services.

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