Although a clear recommendation of early integration of palliative care has already been described, the optimal time point of referral remains unclear . Therefore, we conducted a retrospective analysis to identify factors associated with an “early”, “intermediate” and “late” referral to a SPCC. Our study showed that still most of advanced cancer patients were referred late (< 3 months before death) in their course of disease. This is in line with the study of Wentlandt et al., who described referral practices of Canadian oncologists to specialized palliative care and defined characteristics associated with these referrals. Hereby they showed that 83.3% of advanced cancer patients were referred less than 6 months before death . Likewise the study of Scibetta et al.  showed that from 297 palliative patients 204 (68%) were referred less than 90 days prior to death (late referral). A current study from 2020 from Hausner et al.  compared timing of referral before and after the publication of ASCO recommendation supporting early palliative care referral . They showed that late referrals (less than 6 months to death) decreased from 68.8–44.8%. However, late referrals were still the majority in both groups. Therefore, further attempts should be made to reach out an early referral that might benefit our patients and their families.
Our analysis clearly showed that pain, social care planning problems and psychological distress were indicators for referring to a SPCC among outpatients with advanced cancer. This data show again the importance of a proper assessment of palliative care needs, where physical symptoms might not be the main burden of our patients and their families. This is in line with a systematic review showing that psychological distress is a common recurrent referral criteria for outpatient palliative cancer care . Additionally, a low ECOG Performance Status is an indicator for early referral likewise to the study from Carrasco-Zafra et al. . Furthermore, the quantity of assistance with activities of daily living changed significantly from early to late referral. Both indicators show once more the impact of lost of autonomy in our patients.
Moreover, we detected a significant higher intensity of symptoms like “pain”, “weakness”, “tiredness”, “loss of appetite” in patients who were referred late to specialised palliative care. Social problems like “restriction of daily life“, „overburdening of family” and a higher HOPE global sum score were also frequently associated with late referrals. In a previous study from our CCC, we examined needs and requests of cancer patients in the oncology outpatient clinic for palliative care using a patient reported outcome measurement with MIDOS 2 . Symptoms like “depression”, “anxiety” and “weakness” were indicators for outpatient’s wish for referral to a SPCC . In our study, symptoms like depression or anxiety did not result in an early referral similar to the study of Whadhwa et al. . These results might show the difference between the wish of patient and the reasons for a referrer to actually refer a patient to a specialized palliative care unit. Second, a palliative care nurse rated the questionnaire at first referral to the SPCC. Therefore, further analysis comparing results between self-reported and external assessments would contribute to a better understanding and improvement of patient-centred outcomes. The difference in symptom intensity by early and late referrals are in line with Cheung et al.  and Whadwa et al. . Cheung et al. analysed 1366 outpatients with advanced cancer. In their study, gastrointestinal, lung and breast cancer were the most common primary cancer sites of patients referred to a palliative care cancer center. The most distressful symptoms were “poor general wellbeing”, “decreased appetite” and “fatigue”, similar to our study. In addition, Whadwa et al.  used the Edmonton Symptom Assessment System (ESAS) to compare early (> 12 months before death) with late referrals (< 6 months before death). Patients who were referred late showed a significant worse overall symptom score as well as the symptoms “tiredness”, “nausea”, “drowsiness”, “loss of appetite” and “overall wellbeing”, similar to most of our results. Therefore, an increasing intensity of these symptoms could be an indicator for a timely referral to specialised palliative care.
Furthermore, our study showed that early referrals were associated with the female gender. This is in line with a previous study from the authors Kwon et al. . They compared early referrals (expected survival greater than two years) with late referrals and showed that for example younger patients, female gender and head and neck cancer are indicators for an early referral. Also, a recently study showed that younger age and gynaecologic cancer were more likely to receive a PC referral . The Robert Koch Institute (RKI) documented, that women attend cancer screenings more regularly than men . This might be one reason for the association between the female gender and earlier referral to palliative care. In addition, it was shown that female gender is more frequently associated with suffering from depression and fear. This could be an explanation for the mentioned psychological distress and younger age as indicator for a timely referral.
The presence of ascites in cancer patients is an indicator for a late referral. Many studies documented that malignant ascites correlates with a poor overall prognosis and a deteriorating in quality of life [36, 37]. For example, a retrospective review of 76 patients with malignant ascites by Mackey et al.  from 1996, showed that the median survival was 11 weeks from time of diagnosis. Additionally they showed that the presence of low serum albumin and hepatic metastases were significant indicators of poor prognosis.
Some laboratory parameters like NLR, LDH and CRP have been described as indicators of poor prognosis in oncologic patients [38, 39]. The NLR is described as a factor related to systemic inflammation, which is associated with cancer growth. Current studies from 2020 and 2021 have suggested that a high baseline NLR is an indicator of lower rates of progression-free and overall survival in various tumour entities like breast, lung and gastrointestinal cancers [40–42]. In our study we show that leukocytes, neutrophils, NLR, LDH and CRP are significantly higher in cancer patients who were referred late to a SPCC. The recommendation of these laboratory parameters, some of them well known as prognostic factors, might be further explored in the oncologic palliative care setting as a measure for identifying appropriate candidates for a specialist palliative care referral. There are currently many examples of tools that include both laboratory and clinical or other parameters to assess prognosis [43, 44].
In sum, our data convincingly show that patients with late referrals could have received PC earlier. We propose that not only symptom monitoring, but also other physical (for example the presence of ascites) and laboratory parameters associated with a poor prognosis (like NLR, low serum albumin) might provide useful information for a timely palliative care consultation and therefore its use in the palliative care screening process might be further explored.