Outcomes in elderly patients admitted to the intensive care unit with solid tumors

Cancer is the leading cause of mortality in France, ahead of cardiovascular diseases. In 2015 there were 385,000 new cases of cancer in France, with 149,500 cancer-related deaths [1]. The median age at diagnosis of cancer is 65 years, and the rate of cancer diagnosis increases with age in both males and females [2].

Remarkable advances have been made in the early diagnosis and management of patients with malignancies, resulting in dramatic improvements in overall survival rates [3, 4]. As a result, increasing numbers of oncology patients are admitted to the intensive care unit (ICU), for either life-threatening cancer-related complications, treatment-associated side effects or standard critical care admission indications [5].

Overall, survival rates in critically ill patients with active cancer appear to be increasing [5]. However, studies conducted among patients with hematological malignancies or lung cancer indicate that ICU mortality in these patients is high [6‐8]. In addition, a number of unanswered questions remain, including a lack of follow-up data on patients who survive a stay in ICU, and data on the clinical course and anticancer treatment continuation rates after the critical illness are very limited [8, 9]. Furthermore, there is a lack of data on ICU patients with non-hematological malignancies.

The aim of this study was to assess patient outcomes and identify factors associated with 90-day mortality and antineoplastic treatment resumption in elderly patients with metastatic or non-metastatic solid cancers admitted to the ICU.

A total of 4185 patients were admitted to the ICU over the study period. Of these, 2327 were classified as elderly (age ≥65 years), 332 (14.3%) of whom had a solid tumor, and 262 (11.3%) were included in the final analysis (Fig. 1).

This study provides interesting data about outcomes in elderly patients with active solid tumors admitted to the ICU, who comprised 14.3% of all elderly patients with an ICU admission over the study period (60.3% of these had metastatic disease). The presence of a solid tumor did not increase ICU mortality compared with patients who did not have a solid tumor, but elderly patients admitted to the ICU with active cancer were extremely critically ill. The majority of indications for ICU admission were not related to cancer. More than half of patients with an indication for ongoing cancer therapy had treatment resumed after their ICU stay. The 90-day mortality was 51.9%. We identified high SAPS 2 score and primary tumor site as being significantly associated with death at day 90 on multivariate analysis, whereas previous cancer therapies and performance status were not.

In our study, the ICU mortality rate for critically ill elderly patients with solid tumors was 33.6%, comparable to that in similar patients without cancer. Previous studies assessing the outcome of cancer patients in the ICU reported a wide range of mortality rates, from 24 to 75% [9, 11‐15]. This wide range can be explained by the marked heterogeneity in patient case mix: medical and surgical patients; solid and hematological cancer patients; allogeneic and autologous bone marrow transplant recipients; and patients with and without early limitation of active therapies [5, 16]. In many studies, hematological cancer, medical admissions and limitation of active therapies were associated with worse prognosis [16]. In our study, we focused on patients with solid cancers and we excluded those with early limitation of active therapies.

To date, few studies in this setting have focused on elderly patients. In a registry of 1134 patients aged >65 years with advanced lung cancer admitted to ICUs, the in-hospital mortality was 33% [8], almost identical to the rate in our study. In the registry cohort, age was not associated with mortality, and this was also the case in multivariate analyses from other studies assessing predictors of death in critically ill patients admitting to the ICU with solid cancers [11, 12, 15‐17].

In our cohort, patient prognosis after ICU admission appeared to be associated more with the severity of clinical condition at ICU admission than with the presence of cancer and age, as in most other previous studies [8, 9, 11‐17]. In the Sepsis Occurrence in Acutely Ill Patients (SOAP) study, patients with solid tumors had similar survival to patients without cancer, as was the case in our analysis, although the SOAP study included patients aged <65 years [18]. Also in the SOAP study, hospital mortality increased as the number of organs failing increased, and more than 75% of the subset of patients with more than three failing organs died compared with about 50% of patients without cancer (p = 0.01). In a multicenter study conducted in Brazil (n = 717), higher Sequential Organ Failure Assessment scores were found to be associated with increased hospital mortality on multivariate analysis (odds ratio [OR] 1.25; 95% confidence interval [CI] 1.17–1.34) [11].

We found that primary cancer type was associated with 90-day mortality whereas number of previous cancer treatments was not. This is an area of debate, with recent studies that assessed factors associated with ICU death in cancer patients regardless of age and cancer type showing an inconsistent link between ICU death and cancer [5, 9, 16, 19, 20]; some authors have found association between cancer progression, metastatic status and prognosis [9, 11, 15]. In a large multicenter study including 717 patients (667 with solid tumors and 50 with hematological malignancies), active recurrent or progressive malignancy was associated with increased hospital mortality in multivariate analysis [11, 17]. Another study among patients with solid tumors (n = 162) found that complete or partial remission of the underlying cancer decreased the risk of ICU mortality (OR 0.026, 95% CI 0.002–0.3; p = 0.004) [15]. Our data showed that ICU admission related to tumor progression was not associated with mortality, but was associated with less resumption of anticancer treatment. However, we did exclude patients with early limitation of active therapies, and most admissions were not related to cancer progression. It has previously been shown that some specific causes of admission due to progression of solid tumors are associated with very poor prognosis [21, 22]. As a result, the elderly patients admitted to the ICU in this study might represent a selected group, and we did not assess patients not referred to the ICU by the oncologist or refused by the intensivist.

There is a relative lack of data about links between long-term outcome and anticancer therapy resumption [8, 9]. In our study, the number of patients able to resume antineoplastic therapy was encouraging (52.7%). This rate is high compared to the small amount of existing data. In one study of 1134 patients aged >65 years with active advanced lung cancer, only 19% resumed anticancer therapy after ICU discharge [8]. Another study about critically ill lung cancer patients reported a therapy resumption rate of 37% [9]. Possible reasons for the lower rates in the other studies could be the advanced stage of lung cancer, the high proportion of cancer-related complications and low number of therapeutic options in those patients. In addition, new targeted therapies in oncology and the fact that our cohort included other tumor types could have contributed to the different results between studies. It has been previously reported that there is a link between poor performance status and no resumption of anticancer treatment after an ICU stay [9]. Similarly, we found that gastrointestinal and lung cancer or patient admitted to the ICU because of tumor progression, or with poor performance status were prognostic factors for no anticancer therapy after ICU discharge. One explanation for this could be that patients with tumor progression may be more weakened by an ICU stay, and thus, further cancer therapy might be deemed too intense for them.

This study had several strengths. It is one of the largest cohorts in which long-term mortality of elderly patients with active cancer admitted to the ICU has been determined. Moreover, only patients with solid tumors were included, eliminating high-risk populations (e.g., patients with hematological malignancies. Another strength was the collection of data about tumor and metastatic sites, as well as the number and type of treatments received prior to ICU admission. Furthermore, we include data on resumption of anticancer therapy after ICU discharge, something that has only been reported in a few previous studies and is clinically relevant because it could play a part in assessing whether or not to admit a patient with cancer to the ICU.

Our study also has some limitations that need to be taken into account when interpreting the data. The study was conducted in a single center and had a retrospective design. Also, there were some database limitations, including missing data on biological and clinical variables (e.g., albumin level or performance status) meaning that calculations on the prognostic value of these variables may be affected. Furthermore, our results are only applicable to a subset of similar patients due to selection bias; patients too unwell to be admitted to the ICU were not included, as indicated by the fact that only 15% of our patients were in the ICU because of cancer progression. As a result, the study population had a relatively better general condition with fewer comorbidities, which may explain the good outcomes observed.

Our study results showed that elderly patients (≥65 years) with solid tumor admitted to the ICU had the same mortality rate as similar elderly patients without cancer. In addition, more than half of the elderly cancer patients discharged from the ICU were able to resume anticancer treatment. Factors associated with ICU mortality were related to the patients’ status at ICU admission and not to the presence of metastatic disease or the number of previous anticancer treatments. These findings suggest that early admission of elderly cancer patients to the ICU is appropriate, when necessary.