Impact of adjuvant radiotherapy on the survival of women with optimally resected stage III endometrial cancer in the era of modern radiotherapy: a retrospective study

Abstract

Background: The optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy. Methods: We retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models. Results: One hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy. Conclusions: Modern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer.

Real-World Evaluation of Modern Adjuvant Radiotherapy in Women with Stage IB Endometrial Cancer

“…For apparent uterine-confined endometrial carcinoma, the primary treatment was staging surgery, which included total hysterectomy, bilateral salpingo-oophorectomy, selective or systematic pelvic lymphadenectomy, and peritoneal washings [ 7 , 16 ]. The median dissected lymph nodes number was 16 (range: 0–43).…”

“…Chemotherapy was administered less frequently than radiotherapy in IB patients. Platinum-based regimens plus paclitaxel were commonly given (75%), while other regimens including cisplatin plus doxorubicin (13%), doxorubicin plus ifosfamide (6%), or epirubicin plus cisplatin (6%) were also administered according to the physician’s preferences [ 7 ]. The median number of administered chemotherapy cycles was four (range: 2–6).…”

“…Modern adjuvant radiotherapy for endometrial cancers consists of intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and image-guided VBT, all of which demonstrate equivalent and even superior disease control with reduced treatment-related toxicity and are becoming more widely available [ 7 , 8 , 9 , 10 ]. Modern radiotherapy has the advantages of three-dimensional computed tomography (CT) simulation for organ motion management, Monte Carlo algorithm treatment planning for precise dose distribution, multileaf collimator integration, and cone-beam CT verification of patient position in linear accelerators; this helps to deliver precise radiation dosages to the target while minimizing the exposure to organs at risk, leading to increased locoregional tumor control, decreased radiation-related side effects, and better survival rates than conventional radiation delivery [ 11 , 12 ].…”

Determinants of Sensitivity to Radiotherapy in Endometrial Cancer

“…On the other hand, we identified that the foremost recent studies with chemo- and RT in EC investigate modern variants of radiation therapy such as proton therapy, intensity-modulated radiation therapy (IMRT) and volume-modulated arc radiotherapy (VMAT), alone or in combination with platinum compounds ( Table 2 ), with results yet to be published in most of the cases. Such modern therapies have the advantage of reducing off-target irradiations [ 126 ] and associated secondary effects in EC [ 127 , 128 ]. Moreover, IMRT and VMAT, alone or combined with chemotherapy, have successfully reduced the risks of recurrence and death in non-endometrioid EC.…”

“…Moreover, IMRT and VMAT, alone or combined with chemotherapy, have successfully reduced the risks of recurrence and death in non-endometrioid EC. Patients over 60 years of age as well as those with endometrioid histology, lymphovascular space invasion, and with two or more positive lymph nodes benefitted the most [ 128 ].…”