Rare cancers and cancer of unknown primary: Here's what you should know!

Abstract

In this issue, we have a Special Supplement focusing on rare cancers and cancer of unknown primary (CUP). Of the almost 4 million new cancer cases in Europe per year (Ferlay et al., 2018), about 24% are rare cancers. Rare cancers are defined as those with an incidence of <6/100,000 people per year, according to the Surveillance of Rare Cancer in Europe (RARECARE) consortium (Gatta et al., 2011). CUP refers to a heterogeneous group of metastatic cancers, for which the primary site cannot be identified after diagnostic work-up (Fizazi et al., 2015; Rassy & Pavlidis, 2019). CUP represents about 3%–5% of all cancers; however, it ranks among the top six causes of cancer deaths in Western countries (Pavlidis & Fizazi, 2009; van de Wouw et al., 2002). Both rare cancers and CUP produce several (clinical) challenges, compared to more common cancers, such as breast and prostate cancer. Besides the relative low number of incident cases, they share the absence of a typical, uniform cancer presentation (Komatsubara & Carvajal, 2016; Ray-Coquard et al., 2017). Reasons for the lack of progress and existing challenges are multifactorial and include among others: insufficient public awareness, limited experience and training of primary and secondary health care professionals, deficient screening options for early diagnosis, limited access to appropriate diagnostic and treatment services, and lack of (referral to) tailored supportive, psychosocial care (de Heus et al., 2021; Fernandez, 2007; Gatta et al., 2011). Rare cancers and CUP collectively are not rare. In this Special Supplement of the European Journal of Cancer Care on rare cancer and CUP, we have brought together an assembly of studies and commentaries, focusing on challenges and problems these patients and (health care) professionals are facing. First of all, to increase awareness, but essentially, we still have so much ground to cover. In an extensive systematic review, de Heus et al. (2021) included 57 qualitative and quantitative studies with the aim to summarise unmet supportive care needs of rare cancer patients throughout their disease trajectory, per rare cancer domain, and to identify predictive factors for these unmet needs. Patients most frequently reported unmet needs regarding information provision, psychological support and physical and daily living support. Identified predictors of unmet needs were younger age and higher levels of anxiety and neuroticism. The authors emphasise that health care professionals should be aware of the different unmet needs per rare cancer domain and that these unmet needs should be recognised and individually addressed, starting from diagnosis onwards. In two studies, haematological cancer patients received particular attention. Lindman et al. (2021) developed a multimodal interdisciplinary rehabilitation program (HAPPY), specifically for patients treated with non-myeloablative allogeneic haematopoietic stem cell transplantation (NMA-HSCT). It is a major challenge for these patients to maintain physical and psychosocial functioning and a certain level of participation in society. Patients (n = 30) in the HAPPPY program reported mainly good quality of life, both pre-NMA-HSCT and at 12-month follow-up, despite of presence of ongoing symptoms, such as fatigue after NMA-HSCT, and low cardiorespiratory fitness, both at baseline and follow-up. Long-lasting rehabilitation support is recommended by the authors for this exceptionally frail patient group. Bennink et al. (2021) aimed to explore, using qualitative methods, perspectives and experiences of haematological cancer patients, specifically multiple myeloma (MM) patients, and (health care) experts regarding return to work (RTW) and participation at work. Improvement in survival and disease control has created new perspectives for MM patients, making it more relevant to consider issues, such as social functioning and work ability. Overarching themes drawn from the interviews with patients (n = 9) and experts (n = 15) included: (1) severity of MM diagnosis and treatment impacts upon RTW; (2) step-by-step reintegration facilitates RTW; (3) meaning of work differs between MM patients and experts; and (4) tailored counselling is lacking in experts. Especially patients with lower education, physical limitations and those in physically demanding jobs are expected to benefit from timely and tailored counselling from specialised RTW experts. In two further studies, tumours in the gastrointestinal tract were investigated. Eichler et al. (2021) explored health-related quality of life (HRQoL) in 130 patients from 13 centres, with a gastrointestinal stromal tumour (GIST), compared to the general population, and in GIST patients receiving tyrosine kinase inhibitor (TKI) therapy. GISTs are soft tissue sarcomas that can be located in any part of the digestive system. The authors found a mean global HRQoL score of 63.3 (out of 100 points) in GIST patients and large differences, compared to the general population, regarding social functioning and diarrhoea, and moderate differences regarding financial difficulties, insomnia and emotional functioning. Patients receiving at least their second line of TKI therapy had the highest symptom loads and restrictions in their HRQoL. Patients with gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) generally have a lower HRQoL compared to the general population as well, due to symptoms associated with functioning tumours, as well as treatment-related symptoms. Ronde et al. (2021) performed a systematic review and meta-analysis, including 20 studies. The underlying aim was to provide clinicians easy access to up-to-date evidence on the advantages and disadvantages of available treatment options, as GEPNENs patients may favour HRQoL prospects over prolonged survival. The authors indicated that all explored treatments appeared beneficial for disease stabilisation, while maintaining stable global HRQoL. Yet, they found that high-quality HRQoL reporting in these patients was lacking. Supportive care needs in patients with epithelioid hemangioendothelioma (EHE), a vascular sarcoma, were examined by Husson et al. (2021). About one third of EHE patients has high symptom burden. To be able to tailor supportive health care to highly symptomatic EHE patients, the authors explored data of 115 EHE patients from 20 countries, using the PROFILES registry. Supportive care needs were found in every domain, with the highest score for the psychological domain. Needs were associated with younger age, advanced disease stage and being diagnosed less than 5 years ago. Greater awareness among health care professionals and proper assessment of unmet needs is important, as health care professionals are experts in diagnosis and treatment, but not necessarily in addressing these needs. Epithelioid sarcomas (ES) are an extremely rare and aggressive type of soft tissue sarcoma with heterogeneity in presentation and clinical behaviour, predominantly affecting younger adults. Alves et al. (2021) contributed to this Special Supplement on rare cancers and CUP with a commentary on the evolving management of ES. Diagnosis has become easier, through loss of expression of INI1; however, optimal management of advanced ES remains difficult with limited response to chemotherapy. Prusak et al. (2021) qualitatively explored the psychosocial impact of living with mesothelioma from both the patients' and caregivers' perspectives. Mesothelioma is a rare cancer with a poor prognosis, caused by exposure to asbestos. Themes that emerged from the interviews showed that patients (n = 10) seemed to have an active coping style, which became evident in arrangements they made regarding their forthcoming death. Patients indicated that they did not utilise psychosocial support, even though they experienced problems, such as adaptation issues. Overall, they appeared to have a lack of knowledge of and awareness about what psychosocial support actually entails and described how they primarily dealt with symptoms and problems themselves, mainly through family support. Carers (n = 5) of mesothelioma patients commonly showed a passive coping style. It was found that the offer of psychosocial support to carers differed between peripheral and specialised hospitals, but that their need for this type of support was high. The perspectives and experiences of health care professionals and other relevant stakeholders regarding psychosocial support and palliative care in mesothelioma patients and their relatives was assessed in a qualitative study by Frissen et al. (2021). Also, gaps in current health care and potential improvements were discussed. Participants (n = 16) emphasised in the interviews the importance of accurate, timely and well-balanced information provision, regarding psychosocial support and palliative care, for these patients. A tailored care approach, not only in CoE but in all hospitals, with fluent transitions between primary and secondary cancer care, and palliative care early on in the disease process, are recommended. Shifting our focus towards CUP, one original study and two commentaries have been included in this Supplement. Grewcock et al. (2021) investigated whether a family history of cancer is associated with increased CUP risk. The possible role of genetic susceptibility and shared environmental factors, contributing to increase CUP risk, is hinted at by the extensive evidence for clustering of cancer within families across anatomical sites. Therefore, the authors performed a case cohort analysis using data from the Netherlands Cohort Study, which included a total of 963 CUP cases and 4,288 subcohort members. However, they showed that having a family history of cancer is not an independent risk factor of CUP. The only consistent, but not statistically significant, association observed was a moderately increased CUP risk in participants who reported a sibling with cancer compared to those who did not. Ye et al. (2021) addressed head and neck cancers, specifically squamous cell carcinoma in cervical lymph nodes arising from an undetected primary tumour (SCCUP), in their commentary. Moreover, they emphasise that clinicians who treat head and neck cancer patients should be familiar with diagnostic approaches to SSCUP, and they highlight several techniques. They stress that meticulous work-up of the SCCUP patient is central to the management of these patients, as identification of the primary site improves overall survival. Finally, Loef et al. (2021) stated in their commentary that you must know your enemy in order to win the war. In the case of CUP, it means we need more epidemiological data, in addition to immunological and molecular data, to speed up the slow progress in clinical results. To address CUP patients' extremely poor prognosis, the authors propose a diagnostic work-up of patients with a cancer that is not immediately classifiable. The ultimate goal is enhanced survival of CUP patients. We hope this selection of original studies and commentaries we have presented on rare cancers and CUP will be useful to health care professionals and researchers. Let us make this future patient tomorrow's reality! The authors have no conflict of interest to declare.