Severe symptoms and very low quality-of-life among outpatients newly diagnosed with advanced cancer: data from a multicenter cohort study

Cancer patients experience a large variety of symptoms throughout the course of their disease and it is becoming increasingly recognized that to some extent, symptoms may be relevant already early after diagnosis of advanced cancer for some patients. Kaasa and Loge et al. [1] proposed the use of standardized care pathways and multidisciplinary teams to foster the integration of oncology and palliative care teams already early after diagnosis of advanced cancer to respond timely to patients’ needs with a coordinated approach of specialist teams.

Some studies assessed symptoms and burden of patients with either a large time variation since cancer diagnosis [2] or cancer progression [3]. Others primarily focused on the prevalence or mean intensity of symptoms and quality of life (QoL) in general [4] or at the end of life [3, 5‐7]. Knowing symptom intensity and the QoL early after diagnosis of advanced cancer is highly relevant to optimize cancer care and to allocate resources according to patients’ needs [1].

The aims of the study presented here were therefore to identify (i) how many patients with newly diagnosed advanced cancer suffered from symptoms of severe intensity and very low QoL domains and (ii) which symptoms and QoL domains were the most frequent causes for such suffering [8].

Of 3155 patients screened, 592 were included (see Fig. 1) and complete data was obtained from 481 patients, 111 (18.8%) had to be excluded because the questionnaire was not returned or not assessable for other reasons (e.g., missing data).

The average age was 62.4 years (SD 12.0) and 245 (50.9%) were female. Gastrointestinal cancer (28.5%) and cancer of the respiratory system (26.6%) were the most frequent cancer diagnoses (Table 1). Average scores of POS, HADS, QoL, and symptoms were rather low or moderate. However, role functioning was the most affected functioning item (median 33.3, interquartile range (IQR) 0.0 to 66.7) and fatigue the most burdening symptom (median 55.6, IQR 33.3 to 77.8) in the EORTC QLQ-C30 questionnaire.

Rather than focusing on mean intensity of symptoms, the aims of this the study were to identify (i) how many newly diagnosed outpatients with advanced cancer suffered from symptoms of severe intensity and very low QoL domains and (ii) which symptoms and QoL domains were the most frequent causes for such suffering.

The mean scores for QoL and symptom intensity were generally rather low or moderate, which was comparable to some previous early palliative care (EPC) trials [17‐20]. In the present study, we focused on symptoms of severe intensity or QoL domains that were reported to be very low by the patients. Two-thirds of the patients experienced at least one of such “severe burdens” with a median of two per patient. Role functioning, fatigue, and social functioning were identified as the three most common reasons for such “severe burdens” already shortly after the diagnosis of incurable advanced cancer, with scores being clearly worse than in the normative population [21]. In studies with palliative care patients, fatigue, pain, weakness, appetite loss, anorexia, constipation, anxiety, and depression were identified as burdening symptoms, but in general, only means and SDs are reported in such trials [2, 3, 6, 22‐24]. Functioning items were mostly not assessed in these previous studies except for the study by Lidstone et al. in which cancer outpatients rated their symptoms and concerns [22]. Similar to our results from patients shortly after diagnosis, patients from the study of Lidstone et al. reported role functioning to be problematic as addressed by the items “Not being able to do the things you usually do” and “Relationships with important people in your life” [22].

Our analysis also revealed that one-fifth of the newly diagnosed advanced cancer patients experienced moderate or severe anxiety and depression symptoms and a very low QoL. While normative data for the HADS Anxiety score suggest almost equal distribution compared to the normative population [25], the normative data for the HADS Depression score [25] and the EORTC QLQ-C30 [21, 26] revealed that depression and impairment of QoL was pronounced already in the patients early after diagnosis of advanced cancer in the study at hand.

In the free text of the POS, patients often reported fears from adverse events, e.g., from tumor-directed therapy or the planned diagnostic procedures, which can substantially aggravate depression and anxiety as well as impair patients’ QoL. This finding is important to consider when planning integrated specialist palliative care and oncology cooperations because for providing help for coping with these fears, the basic, primary, or general palliative care expertise of the oncology team is needed to address these specific information needs, to initiate goal-of-care discussions, or to overcome misunderstandings concerning therapeutic or diagnostic maneuvers. Such integration of general palliative care provided by the oncology team is often overlooked in the conceptual development of oncology/specialist palliative care cooperations for EPC [1, 27].

Online Resources 4 and 5 indicated that tumor site and gender might be associated with patients’ burden. In all, women had better POS scores but reported higher values for anxiety and fatigue than male patients which confirms results identified in other studies and underlines the need for a closer look at gender differences in future studies [28‐30].

Most notably, women with breast cancer tended to have better physical and emotional functioning and less fatigue compared to other female cancer patients. The reason for this finding is unclear, but it may be argued, that because of an exceptional long-standing tradition of interdisciplinary, multi-professional, comprehensive breast cancer treatment tradition, these findings may illustrate the potential merits of multi-professional and interdisciplinary comprehensive cancer care.

Patients with central nervous system tumors had a more severely impaired physical, role, and social functioning whereas patients with tumors in the respiratory system reported rather high intensity of symptoms regarding insomnia, yet better values in the POS score.

The importance of screening and identification of unmet symptoms and needs and the subsequent integration of specialist palliative care have been emphasized and may result in better patient-relevant outcomes [31]. The large percentage of severely affected advanced cancer patients with a recent advanced cancer diagnosis yielded in this study adds to the discussion of how burdened patients should be identified [32‐34].

In a Delphi study with nearly 60 international experts, 11 criteria concerning a possible outpatient palliative care referral were found in a consensus process [34]. The criteria involve physical, emotional, and spiritual dimensions. They also include assistance with decision making, patient request, as well as two time-based criteria [34]. These criteria are in accordance with the findings in this study, emphasizing that newly diagnosed advance cancer patients may suffer in the physical, psychological, and social dimensions.

The referral process remains challenging and may depend on hospital structures [1]. Experts agreed in a recent Delphi study with an 86% agreement rate that a combination of both automatic and clinician-based referral may be a meaningful solution [35]. The data presented in this study could serve to discuss and test various concepts for screening models to identify burdening symptoms and patients’ needs.

Two-thirds of patients experienced at least one severe symptom or a very low QoL within the first 8 weeks after diagnosis of advanced cancer with role functioning, fatigue, and social functioning being the three most common reasons for “severe burden” in this EPC population. Tumor site and gender may be considered as additional factors for early routine assessment of patient burden. In light of these findings, the necessity of screening programs and the integration of oncology and a multiprofessional specialist EPC team gains importance to provide high-quality treatment of newly diagnosed advanced cancer patients.