Time-to-Surgery Influences Survival in Early Stage Endometrial Cancer, Study Reveals

A recent study by Cleveland Clinic researchers reveals that delayed time-to-surgery has a negative impact on overall survival of women with early stage endometrial cancer.

In cancer care, time-to-treatment (TTT) is an important quality metric. Longer wait times may permit time for cancer to progress and contributes to increased anxiety and distress for patients and their families.

“Optimizing our patients’ time-to-treatment is a priority for our gynecologic oncology program,” says Peter Rose, MD, Section Head of Cleveland Clinic’s Gynecologic Oncology Program. To better understand how a delay in time-to-surgery (TTS) affects survival rates for patients with endometrial cancer, Cleveland Clinic researchers conducted a retrospective analysis of the National Cancer Database (NCDB). The group sought to determine patient and facility-specific factors associated with TTS in patients with endometrial cancer (EC), and to define the impact of a delay in TTS of more than six weeks on overall survival (OS) by tumor histology and stage.

The study, entitled, “Time to surgery and its impact on survival in patients with endometrial cancer: A National Cancer Database Analysis,” was recently published in Gynecologic Oncology.

Defining the time-to-surgery metric

The NCDB query identified 284,499 patients who were eligible for analysis, based on study criteria. Patients included were those diagnosed with EC between 2004 and 2013 who had either grade 1–3 endometrioid histology (type I) or non-endometrioid histology (type II) and underwent primary surgical treatment.

TTS was defined as the number of days from diagnosis to definitive surgery. For each year of diagnosis, median TTS was calculated by histologic subgroup (type I or type II), overall and by stage. Additionally, 13 baseline characteristics were analyzed, including: year of diagnosis, age, race, Charlson comorbidity score, insurance status, residence, household income, education level, type of facility, distance from facility, EC as first cancer diagnosis, stage and transitional care (i.e., treatment outside the reporting facility).

Results

An increase in TTS was noted for types I and II EC over the study time period, as well as among each disease stage for both types. For type I EC, all 13 variables were significant predictors of TTS except for household income.

In multivariable analysis of type I EC, a delay in TTS of more than six weeks was associated with higher mortality risk in stage I and stage II cancers, but not in stage III or IV cancers. In multivariable analysis of type II EC, TTS of more than six weeks had no impact on mortality risk in stages I, II or III, while patients with stage IV disease had an improved OS.

Findings contradict previous assumptions

Study results reveal that a delay in TTS of more than six weeks was associated with worse OS in type I EC patients with stage I and II disease after controlling for baseline characteristics, contradicting the assumption that delayed treatment of early stage, low-risk EC is not detrimental to patient outcomes.

Conversely, researchers found that patients with type II EC, stage IV, had an improvement in OS with TTS of more than six weeks, suggesting that factors more complex than clinical and socioeconomic issues and not captured in the NCDB may influence outcomes for these patients. This paradoxical relationship has been seen in other cancer such as lung cancer.

Contributors to TTS delays

Socioeconomic factors that were the most clinically meaningful variables predictive of delay in TTS included race, insurance status and facility type.

Additional contributors not captured in the NCDB may be significant, including increased frequency of preoperative diagnostic testing, individual surgeon case load, lack of surgeon access to a robotic surgery platform or availability of specialist gynecologic oncologists.

Implications for practice

Lead study author, Mariam AlHilli, MD, says the growing body of research that identifies TTT as a contributor to OS is important. “We now have evidence from several studies—and especially this large population-based study—that delayed time-to-treatment does influence survival. Even in cancers that are often diagnosed at an early stage and that have a generally favorable prognosis—like endometrial cancer—this makes a significant difference,” she notes. “A cut-off of 6 weeks from diagnosis to surgery in patients with endometrial cancer is an important time-point to be mindful of in order to minimize negative impact of wait times on survival.”

As a result, Dr. AlHilli emphasizes the importance of identifying and addressing underlying barriers. “It is essential that we find ways to reduce time-to-treatment and address the barriers that contribute to this dynamic,” she says. “Although many factors may be patient-specific, in practice, a lot of these barriers may be overcome by addressing logistical issues, such as the need for insurance pre-approval for diagnostic testing and optimizing resources to ensure that patients are seen and undergo surgery in a timely fashion. One example is to have dedicated personnel, such as care coordinators or patient liaisons, who prioritize time-to-treatment.”

At Cleveland Clinic, “we work across disciplines to reduce obstacles in the everyday care of our patients, from coordinating appointments and diagnostic testing, to obtaining financial clearance,” Dr. Rose states. “We also strive to identify institutional barriers to treatment and opportunities for efficiencies.”

Although the focus of this study was endometrial cancer, Dr. AlHilli underscores the broader implications that may apply. “There is cumulating data that time-to-treatment is an important factor regarding patient outcomes in many other cancers. For example, increased time-to-treatment was associated with worsened survival for stages I and II breast, lung, renal and pancreas cancers, and stage I colorectal cancers. In that context, steps to address and overcome influencing barriers may be important to other cancer scenarios as well,” she says.