Considerations for Neoadjuvant Chemotherapy in Metastatic Endometrial Cancer
Faculty in the Division of Gynecologic Oncology at NewYork-Presbyterian/
Dr. Jason Wright
Under the direction of Jason D. Wright, MD, Chief of the Division of Gynecologic Oncology and Vice Chair of Academic Affairs, Department of Obstetrics and Gynecology, Columbia gynecologic cancer specialists have recently led two investigations examining neoadjuvant chemotherapy (NACT) for women with metastatic endometrial cancer.
NACT and Endometrial Cancer: A Look at Overall Survival
While endometrial cancer is often detected early, some 10 to 15 percent of women present with metastatic disease beyond the pelvis and regional lymph nodes at diagnosis. With a poor prognosis, these patients account for a disproportionate number of deaths from endometrial cancer. Five-year survival estimates for stage IV endometrial cancer range from 12 percent to 48 percent.
Primary debulking surgery (PDS) is generally considered the standard treatment of stage IV endometrial cancer. In one series, survival improved from 6.7 months to 17.8 months for patients with optimal debulking. Cytoreductive surgery often requires extensive abdominal resection and is associated with substantial morbidity.
For many solid tumors, the use of neoadjuvant chemotherapy (NACT) before surgical resection has grown and allows for a more limited resection that often minimizes perioperative morbidity. However, few studies thus far have examined the efficacy of NACT for women with metastatic endometrial cancer. Dr. Wright and the Columbia team undertook a study to assess the trends in the use of NACT in women with stage IV endometrial cancer and to compare the survival of women treated with NACT versus patients treated with primary surgical resection.
The cohort study used the National Cancer Database to identify women aged 70 years or younger with minimal comorbidity with stage IV endometrial cancer treated from January 1, 2010, to December 31, 2015. The NACT group included patients who had NACT followed by surgery and those who had initial NACT but did not undergo surgery. The PDS group included patients who underwent primary surgery as a first treatment regardless of whether they received subsequent chemotherapy.
The findings, which were published in the December 2020 issue of JAMA Network Open, showed:
- Within the cohort of 4,890 patients, NACT was used in 952 patients (19.5 percent), whereas 3,938 patients (80.5 percent) underwent primary surgery
- Use of NACT increased from 106 of 661 patients in 2010 to 224 of 938 patients in 2015
- Patients with stage IVB tumors were 31 percent more likely to undergo NACT than those with stage IVA neoplasms; similarly, women with serous carcinomas and other unspecified histologic subtypes were more likely to receive NACT than patients with endometrioid tumors
- In an intention-to-treat analysis of all patients, survival was superior for women treated with NACT for approximately the first 3 months after diagnosis; after 4 months, the survival curves crossed, and survival was superior for women who underwent primary surgery
- In an analysis performed among women who received both surgery and chemotherapy, women who started treatment with surgery, 3,139 of 3,938 (79.7 percent) ultimately went on to receive chemotherapy
- For those who initiated NACT, 555 of 952 (58.3 percent) eventually underwent surgery
The Columbia researchers concluded that the use of NACT for stage IV endometrial cancer has increased over time, and in 2015, nearly one-quarter of women with stage IV endometrial cancer received neoadjuvant therapy. While those who underwent NACT showed decreased mortality immediately following initiation of therapy, longer-term survival was noted for those who underwent primary surgery. These results suggest that PDS increases risk of early death but offers a more favorable long-term prognosis.
Read More
Association of Neoadjuvant Chemotherapy with Overall Survival in Women with Metastatic Endometrial Cancer. Tobias. CJ, Chen L, Melamed A, St Clair C, Khoury-Collado F, Tergas AI, Hou JY, Hur C, Ananth CV, Neugut AI, Hershman DL, Wright JD. JAMA Network Open. 2020 Dec; 3(12): e2028612.
Endometrial Cancer: Comparing NACT to Primary Cytoreductive Surgery
Treatment for stage IV uterine cancer has commonly relied on surgical resection followed by chemotherapy. Most patients with stage IV tumors experience abdominal carcinomatosis, often requiring cytoreductive surgery, a procedure that often leads to significant morbidity. Neoadjuvant chemotherapy with interval cytoreductive surgery has come into practice as an alternative to primary cytoreductive surgery for stage IV uterine cancer with the thinking that this may reduce tumor burden and thus require a less extensive surgery.
To understand the role of NACT in the setting of advanced uterine cancer, Dr. Wright and the Columbia team undertook a population-based analysis to compare NACT to primary cytoreductive surgery among elderly women with stage IV uterine cancer, assessing patterns of treatment, surgical outcomes, and survival.
The investigators drew on the Surveillance, Epidemiology, End Results (SEER) Medicare database to identify women with stage IV uterine cancer treated from 2000 to 2015 and classified them as either undergoing NACT or primary cytoreductive surgery (PCS). Interval cytoreductive surgery after NACT or chemotherapy after PCS was also noted.
Their findings, which were published in the September 2021 issue of Gynecologic Oncology, showed:
- Among 3,037 women, 1,629 (53.6 percent) were treated with primary cytoreductive surgery; 554 (18.2 percent) with NACT; and 854 (28.1 percent) received no treatment
- Use of NACT increased from 9.5 percent to 29.2 percent over the study period
- After NACT, interval hysterectomy was performed in 159 women (28.6 percent), while within the PCS group, 1,052 (64.6 percent) went on to receive chemotherapy
- Extended cytoreductive procedures were performed in 71.7 percent of women who received NACT versus 79.1 percent after PCS
- Complication rates for NACT was 52.8 percent versus 56.2 percent for PCS, with medical complications more frequently seen in the PCS group (39.4 percent versus 28.9 percent)
- No difference existed in cancer specific or overall survival in women who received both chemotherapy and surgery regardless of whether the initial treatment was NACT or PCS
- NACT appeared to be associated with lower perioperative morbidity
The Columbia researchers acknowledge that a growing body of research now suggests that neoadjuvant chemotherapy may be a viable treatment option in select women with metastatic uterine cancer. In particular, the study authors noted, “Hysterectomy is an important component of treatment in women who undergo NACT and those women in whom hysterectomy is omitted have a poor prognosis overall.”
Read More
Use and outcomes of neoadjuvant chemotherapy for metastatic uterine cancer. Wright JD, Huang Y, Melamed A, Albright BB, Hillyer GC, Previs R, Hershman DL. Gynecologic Oncology. 2021 Sep;162(3):599-605.
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Dr. Jason Wright
NewYork-Presbyterian
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