Cancer rates are increasing worldwide with a predicted incidence of 15 million cases in 2015 [1]. Many cancer patients are faced with incurable disease, requiring palliative therapy. In recent years, there has been a significant improvement in overall survival with palliative chemo- and antibody-based therapies in various malignancies, especially colorectal cancer [2–5]. In most clinical studies evaluating new cancer therapies, objective efficacy parameters like overall and progression-free survival as well as safety parameters are typical primary endpoints. In contrast, so-called “PROs” (patient-reported outcomes), defining subjective measures with the focus on patients’ perspectives are less frequently investigated [6]. Only a few studies have explored patients’ attitudes toward therapy, particularly in relation to survival benefit from chemotherapy [7–14]. In the main, these studies indicated that cancer patients accept toxic therapies for smaller survival benefits than do healthy control groups, consisting of doctors, nurses and volunteers [7–11]. As communication in palliative cancer care is challenging, a better understanding of patients’ views on palliative chemotherapy would help to facilitate shared decision making in such difficult treatment situations [15]. Here, we evaluated the subjective impact of common chemotherapy-related side effects. We aimed to find out the survival threshold at which palliative cancer patients would consider chemotherapy worthwhile and identified potential factors influencing the extent of the indicated survival threshold. Patients’ survival expectations were compared to their actual survival times.

Major goals of palliative chemotherapy are to improve patients’ subjective well-being and to prolong survival. In contrast to the latter, the patients’ perspectives on benefits, toxicities and burden are less frequently studied although important for decision making in several aspects – the shared decision making of the patient with his or her treating physician and the allocation of financial or other resources.

In our study population, acne, fatigue, and gastrointestinal (GI) side effects were among the most frequently PRO- grade 3/4 toxicity, with fatigue being the most severe burden as reported by 14.3% of all patients. It is known that skin and GI toxicity are typical grade 3/4 adverse events in multiple phase III chemotherapy trials [5, 25–27]. On the other hand, fatigue has rarely been reported to be a major toxicity in such trials. This may be because fatigue might be a symptom of the underlying malignant disease and therefore cannot be attributed to therapy alone [28, 29]. It is known that 80.0% to 99.0% of patients undergoing chemotherapy report fatigue at some point [30]. Our study showed that fatigue was worse than expected in one third of patients. These findings are in agreement with data from Olver et al [31], who compared patients’ pre-treatment expectations of toxicities with post-chemotherapy experiences. They found that “feeling tired” was among the side effects that occurred in more patients than was initially expected. Interesting in this regard is the fact that fatigue is not detailed on most commonly used consent forms [32]. We believe that fatigue deserves more attention when toxicity of palliative treatment and symptoms of disease are explained to the patient.

Overall, self-reported grade 3/4 toxicity and severe burden rates remained relatively low. Patients seemed to have been well informed about most adverse events (apart from fatigue) prior to treatment. Expectations of side effects were higher than their actual occurrence which supports the findings in other studies [31].

The median actual overall survival in our study was 30.0 months in the CRC and 19.0 months in the non-CRC group. This result exceeds the median overall survival observed in most phase III trials including metastatic CRC and non-CRC cancer [2–5]. A length of time bias together with the fact that we only included patients who had already completed a minimum of three months of palliative chemotherapy, possibly consistent with a potential therapy benefit, may contribute to this finding.

In the current study, patients’ anticipated median survival thresholds were longer (CRC 36.0 months; non-CRC 18.0 months) than described in previous reports [7–11]. This might be influenced by the different surveying methods. Most prior studies used hypothetical situations and classical time trade-off techniques where patients were encouraged to choose between a given number of months, time spans, or risk reduction they would consider a threshold for therapy. In scenarios with mild toxicity, participants would choose therapy for median benefits ranging from 1.5 months [10] to 4.5 months [11]. For more intensive treatment situations, expected survival benefits ranged from 7.5 months [10] up to 12 months [8]. The authors of those studies concluded that patients were willing to undergo treatment for small survival benefits. In contrast, patients in our study were asked to state the exact survival thresholds for which they would repeat chemotherapy. Therefore discrepancies might reflect the difference between preferences in a hypothetical scenario and those in a personally relevant clinical situation [14]. The anticipated survival threshold in our study varied widely (zero to 340 months) which confirms the fact that patients’ expectations are extremely heterogeneous [8, 11, 33].

To our knowledge, this is the first study comparing patients’ survival expectations with their actual survival. Interestingly, the patients’ expected survival significantly exceeded their actual survival time (p=0.003). In a study by Brundage et al, the expectations of more than half of the participants exceeded the estimated, realistic survival benefit defined prior to survey [12]. Chu et al found that 60.0% of their advanced NSCLC patients would prefer a maximum extension of survival with the acceptance of high toxicity [13]. Additionally, in a Korean survey, patients with metastatic solid cancers requested a two-fold longer survival threshold than previous studies had suggested [14]. Similar to our findings of higher expectations in CRC patients, the recently published study of Weeks and colleagues demonstrated that patients’ expectations from palliative chemotherapy are frequently unrealistic and often even include cure [34].

Our results might have been biased by the construction of the questionnaire used in the study. Patients were asked about toxicity and burden from therapy first and then to state the anticipated survival threshold. They might have demanded higher thresholds from therapy after being forced to recall toxicity. Conceivably, some patients might have rather projected their wish for overall survival than survival threshold. Furthermore, the patient group was self-selecting as only 72.3% of the participants would answer the survival threshold question at all. As our patient population had completed a median time of six months of therapy prior to study, which might be interpreted as evidence of a therapy benefit, patients with rapid progression or high levels of toxicity forcing an early discontinuance of therapy might have had an entirely different view on survival threshold. Other patients might have been overwhelmed by the question as it is known that many palliative patients do not give any consideration to end-of-life issues [35, 36].

Factors independently influencing the anticipated survival threshold were disease group, depression, and diarrhea. As depression is known to be positively correlated with hopelessness [37, 38] this might be the explanation why patients in our study with higher HADS-D scores (possible depression) were more willing to repeat therapy for lower thresholds than patients with lower scores. Patients in the non-CRC group were more likely to show abnormal scores in any subscale of HADS, compatible with psychological morbidity. This is in agreement with a number of other studies showing that cancer types with poor prognosis such as lung, pancreatic, or head and neck cancers are associated with the highest rates of psychological distress [39, 40]. As in several other trials, gender [9–12] as well as previous therapy experience [12] did not influence the anticipated survival thresholds. The influence of age on anticipated survival is controversial in the literature. Some authors claim that older patients expect greater benefits [11, 12]. Other studies as well as our own did not show any association between patient age and anticipated survival benefits from palliative chemotherapy [10, 13].

In conclusion, our data show that patients seem to be sufficiently informed about possible adverse events during chemotherapy as occurrence and extent were similar to reported phase III trials. However, fatigue deserves more attention when treatment and symptoms of disease are discussed with the patient. Patients’ expectations from survival with palliative chemotherapy are higher than previously described and exceed their actual survival. Even though new therapies have achieved significant improvements in overall survival, such expectations cannot be met yet. More detailed discussions about survival benefits are necessary prior to therapy [41] to facilitate shared decision making.

Interim results of the current study were presented at 2011 ASCO Gastrointestinal Cancers Symposium, January 20^th - 23^rd 2011, San Francisco, General Poster Session