Early Surgery May Increase Mortality Rates in Endometrial Cancer

Treating endometrial cancer immediately may not be the best option, according to a recent study published in the American Journal of Obstetrics and Gynecology. In fact, the study found that patients who had surgery within the first two weeks after diagnosis had poorer survival outcomes.

Moreover, an extended delay in surgical treatment was also identified to be a risk factor for mortality in low-risk endometrial cancers and was likely associated with poor access to specialty care.

“We suspect that physicians diagnosing endometrial cancer may believe, not unreasonably, that the best thing they can do for those patients is to operate as soon as possible, because if they wait too long the cancer could progress, resulting in a worse outcome,” senior author David I. Shalowitz, M.D., said in a press release.

“But, the results of our study suggest that presurgical care and referring patients to a gynecologic oncologist may be more important,” added Shalowitz, who is a fellow in Gynecologic Oncology at the Perelman School of Medicine at the University of Pennsylvania.

The authors of the study suggested that the target interval between diagnosis and surgical treatment of endometrial cancers is up to eight weeks, though they also stressed that both referral to a surgeon and preoperative optimization should be prioritized over expedited surgery.

The results of the study demonstrated that patients with low-risk cancers had a median survival time of 47.6 months. The five-year crude survival was highest when surgery was performed three weeks after diagnosis, and survival declined thereafter.

Patients who received surgical treatment during the first and second weeks following diagnosis (11.7 percent) had a higher risk of death compared with patients who underwent surgery in the third week after diagnosis. Even after the researchers adjusted for age, stage, race, year of diagnosis and additional clinical and health system characteristics, early surgery in the first and second weeks after diagnosis was still independently associated with a higher risk of death.

When surgery was performed eight weeks postdiagnosis, the mortality risk was significantly higher than baseline and worsened as the interval between surgery and diagnosis increased.

For patients with high-risk cancers, the median survival time was 38.6 months. As with patients with low-risk endometrial cancers, the five-year crude survival was highest, again, when patients underwent surgery in the third week after diagnosis. Survival outcomes continued to decline thereafter.

High-risk patients who had surgery during the first and second weeks after cancer diagnosis (15.9 percent) had a hazard ratio for death of 2.1. Surgery during this interval remained independently associated with death after the study authors adjusted for age, stage, race, year of diagnosis and additional clinical and health system characteristics.

Surgery after the third week postdiagnosis was not correlated with a statistically significant increase in the adjusted risk of mortality, with the exception of an isolated increase seen in the nineteenth week after diagnosis.

The National Cancer Database provided cases of endometrial cancer between 2003 and 2012 for this study. Low-risk (grade 1 and grade 2 endometrioid histologies) and high-risk (grade 3 endometrioid and all other epithelial histologies) tumors were analyzed separately. The researchers limited the overall analysis to only cases for which there were data that surgery was the only modality pursued, or occurred before any hormonal, radiation or chemotherapy treatments.

Given the results showing increased mortality risk accompanying surgery given in the first two weeks postdiagnosis, the investigators compared clinical and process-based factors for patients who had surgery in that short time period with patients who underwent surgery three and four weeks after diagnosis.

Patients with low-risk cancers who received surgical treatment in the first week after diagnosis were more likely to be very young or very elderly (under 45 years or over 85 years), Black, uninsured or with Medicaid insurance, have advanced stage disease and undergo both diagnosis and treatment at the reporting Commission on Cancer (CoC)­—accredited hospital. Plus, these patients were less likely to be treated at high-volume hospitals or be treated with lymphadenectomy.

Patients with high-risk endometrial cancers who had surgery in the first week after diagnosis were more likely to be elderly (over 85), Black, uninsured or with Medicaid insurance, have advanced stage disease, and receive both diagnosis and treatment at the reporting CoC institution. Similar to the low-risk patients, they were also less likely to be treated at high-volume hospitals or undergo lymphadenectomy.

When compared with patients treated in the third or fourth week after diagnosis, 30-day postoperative mortality was significantly higher among patients treated in the first or second week post-diagnosis. For patients with low-risk cancers, this difference was 0.7 percent versus 0.4 percent, and for patients with high-risk cancers, the difference was 2.5 percent versus 1.0 percent.

For patients with low-risk endometrial cancers, the independent associations with added time-to-surgery of at least one week were observed with Black race (1.1 weeks), lack of insurance (1.3 weeks), Medicaid insurance (1.7 weeks) and Charlson-Deyo comorbidity score higher than 1 (one week).

For patients with high-risk cancers, independent associations with added time-to-surgery of at least one week were somewhat similar, as these correlations were observed with lack of insurance (1.4 weeks) and Medicaid insurance (1.4 weeks).

Disease stage was not consistently associated with the interval between diagnosis and surgery for patients with either low- or high-risk cancers.