Although ASCO and SGO have long recommended early integration of PC to improve end-of-life care, practical evidence shows the high underutilization of PC referral in mGCa patients[9, 11, 14, 17]. Intensive care therapies are often provided to mGCa patients when severe treatment-related complications occurred or cancer progressed, highlighting the clinical importance and necessity of PC referral in this vulnerable population[3, 19]. Our analysis suggested that approximately 11.64% patients received inpatient PC, and the rate of PC referral increased from 1.81% in 2003 to 26.30% in 2015 with an average annual increase of 29.08%. Multivariable analysis suggested that medium bedsize, large bedsize, Midwest region, West region, higher Elixhauser comorbidity score, uterine cancer and cervical cancer were related to increased PC use, while urban non-teaching hospitals, metastatic sites from lymph nodes and genital organs were related to lower PC referral.
Overall, about 11.64% mGCa patients with CCT received inpatient PC, more than two times higher than PC rate (5%) in the entire population regardless of CCT reported by Rosenfeld et al.[14]. However, this proportion is still far from satisfactory as all mGCa patients with CCT are candidates for PC referral. It is worthy of note that PC referral has consistently increased by 29.08% from 2003 to 2015. This phenomenon might reflect the improved adherence of oncological guideline by both physicians and patients. Subgroup analysis indicated that increasing trend of PC referral was more pronounced in White and patients admitted to medium bedsize, urban non-teaching and Midwest hospitals, which could be explained by more widely acceptance of PC use in these patients. From the trend charts, we can see that PC rate has a sharp increase since 2009, corresponding to results from previous publications[14, 17]. As aggressive measures such as CCT can reduce quality of life in mGCa patients, this unexpected increase may be partly caused by the landmark ENABLE II trial in 2009 that revealed the effectiveness of PC interventions to improve quality of life in patients with advanced cancer[28].
In consideration of hospital region, patients hospitalized in Midwest hospitals had the highest PC rate (13.30%), followed by South (11.80%), West (11.46%) and Northeast (10.11%), accompanied by the highest APC (33.84%). Multivariable analysis accounting for potential confounders suggested that Midwest region (OR: 1.37) and West region (OR: 1.30) were associated with increased probability of PC referral compared to the Northeast region. This regional disparities in PC use has been previously reported. Milki et al. enrolled mGCa patients who subsequently died during hospitalization and found that patients in Midwest region (OR: 1.37) and West region (OR: 1.30) had increased PC use[17]. Another study focusing on metastatic bladder cancer receiving CCT also described higher PC rate in the West region[22]. Further studies are warranted to illustrate the undelaying mechanism for this geographic disparities and relieve the barriers for lower PC utilization in the Northeast region.
Considering hospital size, we found that both medium bedsize (OR: 1.59) and large bedsize (OR: 1.59) were associated with increased PC use compared to small bedsize. Possible explanation might be that larger hospitals have more dedicated end-of-life specialists to provide PC services. However, relevant researches produced conflicting results on this topic. Rosenfeld et al. included all mGCa cases from 2005 to 2011 NIS database and concluded that bedsize was not a predictor for PC referral[14]. Another study by Milki et al. found that large bedsize was a positive predictor of PC referral (OR: 1.36) in mGCa cases who died in hospital[17]. We hypothesized that the severity of dying status might result this disparity, as mGCa patients receiving CCT or died in hospital represented more severe conditions with significant symptom burden. Large bedsize hospitals are likely to form well-organized PC team and well-established relationship between physicians and mGCa patients who had more severe conditions.
Emerging evidence on whether there were racial disparities of PC use in mGCa patients have been controversial[3, 14–17]. Understand racial and cultural differences in various racial groups may personalize palliative needs and improve delivery of comprehensive cancer care for mGCa patients receiving CCT. It is reported that racial minority (eg, Black or Hispanic) gynecologic cancer patients desired more intensive and invasive end-of-life care[3, 29]. Thus, the minorities are potential candidates for PC delivery from the perspective of end-of-life decision-making. Similar to prior publications[14, 30], we observed that Hispanic patients had the highest rate of PC use (16.83%), followed by Black patients (13.55%) and White patients (11.37%). However, this significant finding disappeared after adjustment for patient-related, cancer-related and hospital-related characteristics. Significantly, Islam et al. used data from the 2016 National Cancer Database and found that Hispanic and Black patients were less likely to utilize PC in metastatic ovarian cancer patients[15]. In our subgroup analysis focusing exclusively on metastatic ovarian cancer patients, we did not observe such racial disparities. Different population groups and data sources may account for this discrepancy, especially when our study involved those receiving CCT during hospitalization. Therefore, more studies are required to provide sufficient evidence to better understand the underlying racial differences and to improve equitable provision of PC among mGCa patients by race.
For cancer type, uterine cancer ranked the first in rate of PC use (14.91%), followed by cervical cancer (14.81%) and ovarian cancer (10.24%). Although ovarian cancer patients has the lowest rate of PC use, PC use has dramatically increased over the study period with the highest APC (31.35%). Lower PC use in ovarian cancer has been previously reported[14, 15]. As we know, degree of malignancy was higher with worse survival in ovarian cancer compared to uterine cancer and cervical cancer[2]. Thus, future efforts are needed to improve and optimize PC referral in metastatic ovarian patients receiving CCT.
The present study used a national-level hospitalized database involving long time spans to explore the temporal trends and predictors for inpatient PC referral in mGCa patients who received frequently used CCT including IMV, TPN, PEG tube, tracheostomy and dialysis for AKF. However, several limitations should also be taken into consideration to accurately interpret our results. First, PC use in the NIS database was defined through ICD-9-CM diagnostic code V66.7. As an administrative database, the NIS may not be able to capture all PC discussions and only those documented by physicians can be recorded. Thus, bias may arise towards the underestimation of exact PC use cases. However, the code was first introduced in 1996 and later was used in several publications, and was proved of moderate sensitivity (66.3–83%) and high specificity (95–99.1%)[26, 27]. Second, this study only focused on specific CCTs that were frequently used in daily clinical practice. Any external extrapolation (eg, to all critically ill mGCa patients) should be interpreted with adequate caution. Third, race information in nearly 12.22% of the included patients was unknown. Although certain limitations, the present study provides new evidence and more insights into the understanding of PC referral in mGCa patients receiving CCT.
This analysis suggested that approximately 11.64% patients received inpatient PC. However, this proportion is still far from satisfactory. Further studies are warranted to clearly illustrate the barriers for PC and finally improve the delivery of optimal end-of-life care for mGCa patients who receive inpatient CCT, especially for those diagnosed with ovarian cancer or admitted to small scale and Northeast hospitals.