Introduction: Early integration of palliative care and advance care planning (ACP) play an increasingly important role in the treatment of patients with advanced cancer. Advance directives (ADs) and patients’ preferences regarding end-of-life (EoL) care are important aspects of ACP. In the outpatient setting, the prevalence of those documents and EoL care wishes is not well investigated, and changes in the longitudinal course are poorly understood. Methods: From June 2020 to August 2022, 67 outpatients with advanced solid tumors undergoing palliative cancer therapy were interviewed on the topic of ACP in a longitudinal course. From this database, the prevalence of ADs, healthcare proxy, EoL care wishes, and the need for counseling regarding these issues were collected. In addition, EoL care wishes were examined for their stability. Results: Fifty-one patients (76.1%) reported having ADs, and 41 patients (61.2%) reported having a healthcare proxy. Nineteen patients (37.3%) with ADs and 11 patients (68.7%) without ADs indicated a wish for counseling. Reported EoL care wishes remained stable over a period of approximately 6 months. Nevertheless, intraindividual changes occurred over time within the different EoL care preferences. The desire for resuscitation and dialysis were significantly higher in men than in women (resuscitation: 15 of 21 men [71.4%] versus 9 of 22 women [40.9%], odds ratio [OR] 3.611, 95% confidence interval [CI], 1.01–12.89, p = 0.048; dialysis: 16 of the 23 men [69.6%] versus 9 of the 25 women [36.0%], OR: 4.063, 95% CI: 1.22–13.58, p = 0.023). Conclusion: Our results show a reasonably high percentage of ADs and healthcare proxies in our study cohort. The observed stability of EoL requests encourages the implementation of structured queries for ADs and healthcare proxy for outpatients undergoing palliative treatment. Our data suggest that gender-specific characteristics should be further investigated in this context.

Numerous trials evaluating the early integration of palliative care have shown benefits in different domains for patients with advanced cancer. Consequently, national and multinational guidelines were adopted, and goals such as early preparation of advance directives (ADs) with or without a power of attorney for healthcare decisions were set [1‒5]. Research in cancer populations shows that patients without ADs receive more aggressive therapy at the end-of-life (EoL; including chemotherapy) and die more often in the hospital than at home [6, 7]. Furthermore, relatives and other caregivers experience higher levels of stress if the patient’s will is unknown and decisions have to be taken according to the presumed patient’s will [8]. This burden on caregivers can even increase their own mortality [9].

In a German single-center study conducted between 2013 and 2014, only 23% of the patients who were treated in the intensive care unit had ADs and/or healthcare proxy documents present in the hospital record. Furthermore, around 40% of those documents were inconclusive due to incompleteness [10]. An investigation on the oncology ward at the University Hospital of Munich published in 2017 found that the limitation of treatment was documented only 6 days before death on average [11]. Besides the ethical and medical need for knowing the patients’ will, some data indicates that advance care planning (ACP) can reduce healthcare costs by decreasing hospitalizations including treatment in intensive care [12, 13]. The low prevalence of ACP-related documents might be due to the reluctance of many physicians to promote conversations about presumed survival outcomes and EoL care. This is even more unfortunate as compelling data show that EoL discussions lead to less aggressive medical care and earlier hospice referrals and may even strengthen the doctor-patient relationship [14, 15]. Furthermore, one might argue that treating physicians have an ethical duty to offer patients conversations about EoL care as there is ample evidence that these can be beneficial with regard to patients’ autonomy, quality of life, and fair opportunity, while conclusive evidence for major harm is lacking [16].

Despite the increasing data and practice guidelines, many details remain unclear: When is the best time to address questions about EoL care preferences? Who should discuss these? What is the best setting for those conversations [17]? Also, do attitudes and wishes about EoL care remain stable over time? Based on this assumption, the signing of documents such as ADs is often promoted early on. There is data supporting this concept, but noteworthy is that most of the trials done so far are based upon questionnaires on hypothetic scenarios [18]. Furthermore, evidence suggests that healthy individuals cannot predict their reactions to future illnesses correctly [19].

In this prospective, observational study conducted at a comprehensive cancer center, we promoted discussions about EoL care preferences and ADs for outpatients with incurable cancer. The aim was to raise awareness about the topic of ACP, assess the prevalence of healthcare documents, and investigate how stable preferences for EoL care remain over time. Furthermore, we aimed to elucidate the impact of patient-related and practitioner-related factors influencing the stability of EoL care preferences.

Study Procedure

This prospective, non-randomized, and non-interventional observational study was conducted at the University Cancer Center Leipzig (UCCL), Germany. From June 2020 to August 2022, outpatients were interviewed on ADs, healthcare proxies, and EoL care wishes in a longitudinal course. Inclusion criteria were: ≥18 years old, treated for incurable cancer in palliative intent, signed informed consent, and being able to understand and answer questions. The study protocol was approved by the ethics committee of the University of Leipzig Medical Center, approval number [182/20-ck].

The initially intended study size was 100 patients. The sample size was chosen based on feasibility considerations rather than on a predefined biometric hypothesis.

Data Collection and Outcome Measures

Two specifically designed questionnaires were used: one was given to the patient and the other one to the treating physician. The patient questionnaire contained questions on the existence of ADs, a healthcare proxy, the need for medical advice on these topics, and EoL care preferences (i.e., resuscitation, treatment on the intensive care unit, machine-assisted ventilation, dialysis, parenteral nutrition). Additionally, sociodemographic data were retrieved. If the questionnaire indicated a wish for medical advice or help with the preparation of an AD or healthcare proxy, an appointment in the palliative care service at the UCCL was made.

The physician questionnaire captured the patient’s Eastern Cooperative Group (ECOG) performance status, a question on the expected survival duration (0–6 months, 6–12 months, 12–24 months, and >24 months), and treatment goals such as prolongation of the survival time and maintenance or improvement of quality of life. Patients and physicians were asked to fill out the questionnaire at the time point of study inclusion (t1) and 6 months thereafter or after change in therapy (t2). A change of therapy was defined as a new drug regimen or termination of anti-tumor therapy due to disease progression, treatment intolerance, or a change in treatment goals. Patient’s records were screened for such changes every 2 weeks using the electronic patient file.

Statistical Analysis

All collected data were prepared in Excel (Microsoft Excel 2016 Version 16.0.5332.1000) and processed in SPSS (IBM SPSS Statistics Version 27.0.1.0) for statistical analysis. Descriptive statistics were used to analyze demographic and clinical variables of the patients, the prevalence of ADs, healthcare proxies, and EoL care wishes. The different items of the questionnaires were tested for correlations using two-sided Fisher’s exact tests and χ2 tests for categorical variables. Binary logistic regression was applied to determine the odds ratio for associations of sociodemographic data and EoL care wishes. Only data at survey time t1 were considered. Only the response options “agree” and “disagree” were included in this analysis, while the answer “don’t know” was not included in these analyses. To examine the stability of EoL care wishes over the longitudinal course, a χ2 test and Fischer’s exact test were performed including only those patients from whom data were available at times t1 and t2. Thirty-three months after the start of the study, the predicted survival information provided by the physicians at time t1 was compared with the actual survival of the patients using descriptive statistics. Actual survival was determined using the electronic patient record. In addition, predicted and actual survival were tested for correlation using Fisher’s exact test.

Sample Characteristics

Between June 2020 and February 2022, a total of 210 patients were screened, and 67 patients agreed to participate. Of these 67 patients, 34 were interviewed a second time at t2. The other 33 patients were not reinterviewed due to the death of the patient (n = 27), switching to a curative concept (n = 2), or because the patient did not respond after contacting (n = 4; see Fig. 1). The baseline characteristics of the study patients as well as the information about ECOG, survival prognosis, and therapy goals provided by the attending physician can be found in online supplementary Table 1 (for all online suppl. material, see https://doi.org/10.1159/000538112).

Fig. 1.

Flow diagram of the study patients.

Fig. 1.

Flow diagram of the study patients.

Close modal

Prevalence of Advance Directives, Healthcare Proxy, and Need for Counseling

At t1, 51 patients (76.1%) reported having an AD. Forty-one patients (61.2%) reported having a healthcare proxy. Of the 51 patients with ADs, 19 patients (37.3%) had a desire for counseling, and 2 patients indicated a desire for future counseling. Among the 16 patients without ADs, 11 patients (68.7%) had a desire for timely counseling, and 5 patients (31.2%) indicated a desire for future counseling or wanted to be asked again in the future. When counseling was requested, an appointment was made with the palliative care service in 90.6% of the cases, and counseling was provided in 81.3% of the cases during the follow-up period.

End-of-Life Care Wishes

Data on the EoL care wishes at t1 can be found in Table 1. No significant changes in EoL wishes were seen between t1 and t2 (resuscitation: p = 0.567, dialysis: p = 0.649, intensive therapy: p = 0.957, machine-assisted ventilation: p = 0.818, parenteral nutrition: p = 0.954; 95% CI). Nevertheless, some intraindividual changes were noted: for “resuscitation” we documented a total of 11 changes (32.4%); for “dialysis,” 12 changes (35.3%); for “intensive care therapy,” “machine-assisted ventilation” and “parenteral nutrition” 13 (38.2%), 16 (47.1%), and 14 changes (41.2%), respectively (online suppl. Table 2; Fig. 1). Patients without therapy changes were interviewed on average 7.5 months (SD ± 1.6) after baseline. Patients with therapy changes were interviewed on average 8.1 months (SD ± 3.3) after baseline and 2.8 months (SD ± 2.6) after the change in therapy.

Table 1.

End-of-life care wishes at t1

VariableStudy participants at t1 (n = 67)
End-of-life care wish: resuscitation, n (%) 
 Resuscitation 24 (35.8) 
 No resuscitation 19 (28.4) 
 Don’t know 23 (34.3) 
 Missing 1 (1.5) 
End-of-life care wish: dialysis, n (%) 
 Dialysis 25 (37.3) 
 No dialysis 23 (34.3) 
 Don’t know 18 (26.9) 
 Missing 1 (1.5) 
End-of-life care wish: intensive therapy, n (%) 
 Intensive therapy 29 (43.3) 
 No intensive therapy 16 (23.9) 
 Don’t know 21 (31.3) 
 Missing 1 (1.5) 
End-of-life care wish: machine-assisted ventilation, n (%) 
 Machine-assisted ventilation 20 (29.9) 
 No machine-assisted ventilation 25 (37.3) 
 Don’t know 20 (29.9) 
 Missing 2 (3.0) 
End-of-life care wish: parenteral nutrition, n (%) 
 Parenteral nutrition 21 (31.3) 
 No parenteral nutrition 28 (41.8) 
 Don’t know 17 (25.4) 
 Missing 1 (1.5) 
VariableStudy participants at t1 (n = 67)
End-of-life care wish: resuscitation, n (%) 
 Resuscitation 24 (35.8) 
 No resuscitation 19 (28.4) 
 Don’t know 23 (34.3) 
 Missing 1 (1.5) 
End-of-life care wish: dialysis, n (%) 
 Dialysis 25 (37.3) 
 No dialysis 23 (34.3) 
 Don’t know 18 (26.9) 
 Missing 1 (1.5) 
End-of-life care wish: intensive therapy, n (%) 
 Intensive therapy 29 (43.3) 
 No intensive therapy 16 (23.9) 
 Don’t know 21 (31.3) 
 Missing 1 (1.5) 
End-of-life care wish: machine-assisted ventilation, n (%) 
 Machine-assisted ventilation 20 (29.9) 
 No machine-assisted ventilation 25 (37.3) 
 Don’t know 20 (29.9) 
 Missing 2 (3.0) 
End-of-life care wish: parenteral nutrition, n (%) 
 Parenteral nutrition 21 (31.3) 
 No parenteral nutrition 28 (41.8) 
 Don’t know 17 (25.4) 
 Missing 1 (1.5) 

The existence of an AD had no significant effect on the stability of EoL care wishes in our study cohort (resuscitation: p = 0.333, dialysis: p = 0.152, intensive therapy: p = 0.124, machine-assisted ventilation: p = 0.316, parenteral nutrition: p = 0.402; 95% CI). Likewise, the existence of a healthcare proxy showed no significant effect (resuscitation: p = 0.714, dialysis: p = 0.868, intensive therapy: p = 0.703, machine-assisted ventilation: p = 0.929, parenteral nutrition: p = 0.565; 95% CI).

Gender Differences

At t1, 15 of 21 men (71.4%) and only 9 of 22 women (40.9%) indicated a wish for resuscitation (odds ratio [OR] 3.611, 95% CI: 1.01–12.89, p = 0.048). A similar result was observed for dialysis at t1: 16 of the 23 men (69.6%) and 9 of the 25 women (36.0%) (OR: 4.063, 95% CI: 1.22–13.58, p = 0.023) wanted to receive this treatment. A non-significant strong trend towards more willingness to receive intensive therapy was noted in men, as for machine-assisted ventilation and parenteral nutrition (see Fig. 2; online suppl. Table 3).

Fig. 2.

Gender differences in EoL care wishes at baseline. Significant difference: *<0.05.

Fig. 2.

Gender differences in EoL care wishes at baseline. Significant difference: *<0.05.

Close modal

Predicted and Actual Survival

At the time of data analysis, a total of 38 patients (56.7%) had died, 14 patients had an unknown survival status (20.9%), and 15 patients (22.4%) were alive. Of the 38 patients who died, the survival prediction as documented by the treating physicians at t1 was correct in 9 patients (23.7%) and incorrect in 29 patients (76.3%; Fig. 3). The prediction was considered incorrect if the physician’s estimate did not match the category (0–6 months, 6–12 months, 12–24 months, or >24 months). Of those estimates, 19 (65.5%) were too optimistic. Fisher’s exact test showed no significant correlation between survival prediction at time t1 and actual survival (p = 0.059).

Fig. 3.

Predicted (light gray) and actual survival (dark gray) of the study patents who died within the follow-up period.

Fig. 3.

Predicted (light gray) and actual survival (dark gray) of the study patents who died within the follow-up period.

Close modal

Prevalence of Advance Directives, Healthcare Proxy, and Need for Counseling

In our study, we found a relatively high prevalence of ADs (76.1%) and/or a healthcare proxy (61.2%) among our patients. This is a larger proportion than reported in other studies; in a comparable cohort, McDonald et al. [20] found only 55% and 49%, respectively. Hubert et al. [21] examined the prevalence of ADs in a German outpatient cancer clinic in 2011 and 2012, that is 3 years after enacting a new law supporting ADs in Germany. Here, they found only 31% of the patients indicating having ADs. In a 2014 survey of the German population, though, 51% of respondents over the age of 60 stated that they had an AD [22]. Our result is encouraging and might indicate an increasing awareness in the German public since the change in legislation but could also be driven by a selection bias. It might be assumed that patients who pay attention to the topic of ACP were more likely to participate in our study. Among patients without AD, approximately 70% indicated the wish for timely counseling. This is in line with a German study where 63% of cancer patients expressed their wish to discuss EoL care with their physicians [23].

Stability of Treatment Preferences

Stability of treatment preferences regarding EoL care is a main assumption for encouraging individuals to document their will in advance. In our study, we found that preferences are stable in the course of treatment for the majority of patients. Within the subgroup of patients who documented a change in treatment preferences, there was no trend towards forgo or endorse invasive therapy. These findings are in line with the published evidence [18]. The existence of an AD and/or healthcare proxy had no significant effect on the stability of EoL care wishes. Though there is evidence that the stability of preferences is greater for patients who had engaged ACP [24, 25], we have to keep in mind that a structured ACP comprises more than those two documents that were queried in our study.

According to literature, the severity of the underlying illness, changes in health status, or the experience of hospitalization can lead to a new perspective regarding EoL treatment wishes [26]. Nevertheless, the observed stability of EoL wishes in our study makes it encouraging to rely on EoL care documents throughout the course of treatment.

Gender Difference

An interesting finding in our study was that the wish for resuscitation and dialysis was higher in men than in women. Though there is emerging evidence on gender differences in medicine, little is known about sex-specific treatment preferences in the EoL setting [23]. In a North American trial, inpatients were asked about their attitudes regarding ACP and dying. Perkins et al. [27] reported that men tend to expect harm from the system, while women rather anticipated benefit. Ke et al. [28] found that sex correlates with the EoL preferences in older hospitalized patients (n = 55) in Taiwan. In a more recent trial, 186 cancer patients were asked about their preferences for EoL discussions. Seifart et al. [23] found a higher level of anxiety in women but also a higher request to discuss EoL care issues compared to men (77% vs. 50%). Furthermore, women are more likely to complete ADs [29]. This could be one reason why men tend to receive more aggressive EoL therapy and why males that have not discussed EoL care are more likely to receive treatment on ICUs in their last week of their lives [30]. However, there are also data that do not confirm any gender difference in EoL care preferences or the completion of ADs, hospital care, and costs, respectively (e.g., [31‒33]).

Other Aspects

It has been observed that physicians tend to be too optimistic about their patients’ prognosis [23, 34, 35]. Our data support this finding: physician’s expectation was wrong in more than 75%, being too optimistic in most cases. This circumstance may further explain why physicians have EoL conversations too infrequently or too late.

Limitations and Strengths

Major limitations of our study are the monocentric design and the relatively small sample size. The dropout rate was high which resulted in an even smaller number of completed questionnaires at time t2. Another limitation is a potential selection bias: mainly patients who already had interest in ACP or related topics may have participated. Additionally, no random selection procedure was used. Furthermore, we investigated a relatively heterogenous patient cohort in terms of cancer diagnosis, applied therapies, and prognosis. Another potential limitation is the relatively short observational period of 6 months. This may be too short to detect significant differences. However, a longer duration would likely result in an even higher dropout rate due to mortality.

However, the study also has strengths: above all, it is a prospective conduct, and its implementation in the clinical routine of a university cancer center allows for getting up-to-date and authentic replies from patients treated in the circumstances of contemporary oncology. The design and conduct also allowed for testing the feasibility of asking for ADs, healthcare proxy, and EoL care wishes, as well as the coordination of ACP counseling when desired. We would also like to point out that few studies on ACP in outpatients have been conducted so far.

Structured query of advance care documents and EoL care wishes of patients being treated for advanced cancer in an outpatient setting was revealed to be feasible. More patients than in previous studies had documented ADs, and EoL care preferences remained relatively stable over a period of up to 8 months, despite major changes in treatment during this time period. Our data suggest that gender-specific characteristics need to be taken into account in this context.

We would like to thank Holger Bogatsch for his statistical advice.

This study protocol was reviewed and approved by the Local Ethics Committee (University Hospital Leipzig) on May 12, 2020. Written informed consent was obtained from participants (or their parent/legal guardian/next of kin) to participate in the study.

The authors have no ethical conflicts to disclose. F.L. has received lecture, expert opinion, or consulting fees from Amgen, Astellas, Astra Zeneca, Bayer, BioNTech, BMS, Daiichi Sankyo, Eli Lilly, Elsevier, Falk Foundation, Incyte, Merck, MSD, Novartis, PAGE, Roche, Servier, Springer-Nature, and StreamedUp. Research projects not related to this study are supported by BMS and Gilead. All other authors did not report any potential conflicts of interest.

The authors have no external funding sources to declare.

T.G., N.H., A.S., H.F., and F.L. have made substantial contributions to the conception and design of the study. N.H., T.G., and A.S. contributed to the collection of the data. N.H. and T.G. analyzed and interpreted the data. All authors read, revised, and approved the final manuscript.

Additional Information

Thomas Golombek and Nora Hegewald contributed equally to this manuscript as co-first authors.

All data generated or analyzed during this study are included in this article and its supplementary material files. Further inquiries can be directed to the corresponding author.

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