The role of adjuvant treatment for early-stage uterine clear cell carcinoma (405)

Objectives: Uterine clear cell carcinoma (UCCC) is a rare histologic subtype of endometrial carcinoma (EC) that is associated with early metastasis, chemoresistance, and poor survival. Due to the aggressive behavior of UCCC and the inability to perform prospective clinical trials for this rare tumor type, adjuvant treatment choices for stage I and II UCCC are often made at the provider’s discretion. Our objectives were to determine if adjuvant chemotherapy (CT), radiation therapy (RT), or both were associated with differences in recurrence-free survival (RFS) and overall survival (OS) in stage I and II UCCC confirmed by gynecologic pathology review. Methods: All patients with stage I and II UCCC between 2006 and 2019 were identified via a single institution pathology database. Electronic medical records were used for demographic and clinical- pathologic data. All cases were reviewed by a gynecologic pathologist. Cases of both pure UCCC and mixed non-serous UCCC were included due to prior evidence that mixed UCCC outcomes are driven by the clear cell (CC) component. RFS and OS were analyzed using Kaplan-Meier (KM) failure functions and a Cox proportional hazards (PH) model. Results: A cohort of 71 patients was identified, including 39 (55%) pure UCCC and 32 (45%) mixed UCCC. Most patients were FIGO stage IA (77.5%). Mixed UCCC tumors ranged from 2-90% CC. Among 32 patients with mixed UCCC, 30 (94%) had endometrioid/CC, and two (6%) had endometrioid, CC, and mucinous histology. Of 58 (82%) patients receiving adjuvant therapy, 43 (61%) received CT, 50 (70%) received RT, and 35 (49%) received both. Recurrences were rare, with one local, three regional, and three distant recurrences in the cohort. Deaths were also rare (n=9) and most likely to be cancer-related (n=4). The Median follow-up time was 1078 days. The 5-year RFS was 85% (95% CI: 70-93%) and 5-year OS was 88% (95% CI: 74-94%). 5-year RFS and OS among patients with and without RT were 88% (95% CI: 39-98%) versus 85% (95% CI: 71-93%) and 88% (95% CI: 62-97%) versus 87% (95% CI: 68-95%). 5-year RFS and OS among patients with and without CT were 82% (95% CI: 0.64-0.92) versus 94% (95% CI: 65-99%) and 90% (95% CI: 75-96%) versus 79% (95% CI: 32-95%). There was no difference in RFS among patients receiving no or less than six cycles of CT (n=38) versus patients who received six cycles (n=32) (HR: 0.5, 95% CI: 0.1-2.4). OS was significantly improved for patients who received six cycles of CT versus patients who received no or less than six cycles of CT (HR: 0.1, 95% CI: 0.01-0.7). On univariate analysis, receiving six cycles of CT was predictive of OS. No other variables were statistically significant; however, lymphovascular space invasion and >2 medical comorbid conditions were included in the Cox PH multivariable analysis given their clinical significance. Adjuvant CT remained a significant predictor of improved OS (HR: 0.1, 95% CI: 0.01-0.8) when controlling for these clinically significant factors. Conclusions: In this cohort, OS was significantly improved with six cycles of CT, and CT remained a significant predictor of OS on multivariable analysis. While additional studies are needed, our findings support a full course of adjuvant CT in patients with early-stage UCCC. Objectives: Uterine clear cell carcinoma (UCCC) is a rare histologic subtype of endometrial carcinoma (EC) that is associated with early metastasis, chemoresistance, and poor survival. Due to the aggressive behavior of UCCC and the inability to perform prospective clinical trials for this rare tumor type, adjuvant treatment choices for stage I and II UCCC are often made at the provider’s discretion. Our objectives were to determine if adjuvant chemotherapy (CT), radiation therapy (RT), or both were associated with differences in recurrence-free survival (RFS) and overall survival (OS) in stage I and II UCCC confirmed by gynecologic pathology review. Methods: All patients with stage I and II UCCC between 2006 and 2019 were identified via a single institution pathology database. Electronic medical records were used for demographic and clinical- pathologic data. All cases were reviewed by a gynecologic pathologist. Cases of both pure UCCC and mixed non-serous UCCC were included due to prior evidence that mixed UCCC outcomes are driven by the clear cell (CC) component. RFS and OS were analyzed using Kaplan-Meier (KM) failure functions and a Cox proportional hazards (PH) model. Results: A cohort of 71 patients was identified, including 39 (55%) pure UCCC and 32 (45%) mixed UCCC. Most patients were FIGO stage IA (77.5%). Mixed UCCC tumors ranged from 2-90% CC. Among 32 patients with mixed UCCC, 30 (94%) had endometrioid/CC, and two (6%) had endometrioid, CC, and mucinous histology. Of 58 (82%) patients receiving adjuvant therapy, 43 (61%) received CT, 50 (70%) received RT, and 35 (49%) received both. Recurrences were rare, with one local, three regional, and three distant recurrences in the cohort. Deaths were also rare (n=9) and most likely to be cancer-related (n=4). The Median follow-up time was 1078 days. The 5-year RFS was 85% (95% CI: 70-93%) and 5-year OS was 88% (95% CI: 74-94%). 5-year RFS and OS among patients with and without RT were 88% (95% CI: 39-98%) versus 85% (95% CI: 71-93%) and 88% (95% CI: 62-97%) versus 87% (95% CI: 68-95%). 5-year RFS and OS among patients with and without CT were 82% (95% CI: 0.64-0.92) versus 94% (95% CI: 65-99%) and 90% (95% CI: 75-96%) versus 79% (95% CI: 32-95%). There was no difference in RFS among patients receiving no or less than six cycles of CT (n=38) versus patients who received six cycles (n=32) (HR: 0.5, 95% CI: 0.1-2.4). OS was significantly improved for patients who received six cycles of CT versus patients who received no or less than six cycles of CT (HR: 0.1, 95% CI: 0.01-0.7). On univariate analysis, receiving six cycles of CT was predictive of OS. No other variables were statistically significant; however, lymphovascular space invasion and >2 medical comorbid conditions were included in the Cox PH multivariable analysis given their clinical significance. Adjuvant CT remained a significant predictor of improved OS (HR: 0.1, 95% CI: 0.01-0.8) when controlling for these clinically significant factors. Conclusions: In this cohort, OS was significantly improved with six cycles of CT, and CT remained a significant predictor of OS on multivariable analysis. While additional studies are needed, our findings support a full course of adjuvant CT in patients with early-stage UCCC.