Survival after relapse in patients with endometrial cancer: results from a randomized trial☆ (original) (raw)

Treatment of vaginal recurrence in endometrial cancer: A review

Acta Obstetricia et Gynecologica Scandinavica, 1996

Background. We have reviewed the literature concerning vaginal recurrence in endometrial cancer with emphasis on prognostics and therapeutic results. Compared to the overall outcome of recurrences (1 1-17 per cent survive more than 3-19 years) the survival rate of strictly vaginal recurrence appears significantly higher (up to 60-70 per cent survive more than 5 years). However, the prognosis deteriorates significantly in cases where recurrences prove to be more widespread. Other factors towards predicting a poor outcome are high age, high stage, high grade, detection of papillary carcinoma, rapid recurrence. location to the lower part of vagina, large tumorsize, and previous radiation. Methods. Different methods of initial treatment and cross-relations between most prognostic factors renders any ranking of prognostic factors almost impossible. Results. Standard treatment of vaginal recurrence including combined external and intra vaginal radiation used for decades have been unable to improve survival rate. Conclusion. We suggest a more individualized treatment based on exact delineation of the disease.

Treatment Failure in Endometrial Carcinoma

International Journal of Gynecological Cancer, 2014

Objective: Our aim was to investigate the outcomes and prognostic factors after treatment failure of endometrial cancer. Methods: A total of 923 endometrial cancer patients were treated between 2000 and 2010, of which 109 experienced treatment failure. Treatment failure was defined as relapse after complete removal of all cancerous lesions or persistent/progressive disease despite treatment. Variables including clinicopathological features at initial treatment, type of primary treatment, failure pattern, salvage treatment, and outcomes were analyzed. Kaplan-Meier survival curves were compared with log-rank test. Cox proportional hazards regression model was used to identify significant prognostic factors. Results: Eighteen cases with persistent/progressive disease died shortly from primary diagnosis (1Y23 months). The remaining 91 patients had recurrences in vagina only (8.8%), pelvis (3.3%), distant (63.7%), and combined pelvic-distant sites (24.2%). Median time to recurrence was 13.3 months (3.2Y97.2 months). The median follow-up after recurrence of survivors was 60.5 months (10.6Y121.7 months). The median survival after recurrence (SAR) was 20.3 months (1.9Y121.7 months) with 5-year SAR rate of 32.4%. By multivariate analysis, initial stage II to IV (hazards ratio [HR], 3.41; 1.53Y7.60; P = 0.003), type II histology (HR, 2.50; 1.28Y4.90; P = 0.008), positive peritoneal cytology (HR, 2.23; 1.07Y4.68; P = 0.033), and recurrence at multiple sites (HR, 2.51; 1.30Y4.84; P = 0.006) were significantly associated with poor SAR. The 5-year SAR rates in patients with solitary vaginal, nodal/ liver, or pulmonary/bony recurrence were 83.3%, 50.5%, and 24.2%, respectively. Ten cases with resectable or irradiatable recurrence at multiple sites or multiple relapses attained SAR greater than 5 years after multimodality salvage therapy. Conclusions: Initial stage II to IV, type 2 histology, positive cytology, and recurrence at multiple sites were significant poor prognostic factors. Curative intent salvage therapy remains a viable option for cases with resectable or irradiatable multiple recurrences and solitary distant metastasis.

Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial

Lancet Oncology, 2019

Background The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis. Methods In the multicentre randomised phase 3 PORTEC-3 trial, women with high-risk endometrial cancer were eligible if they had International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion or lymphovascular space invasion, or both; stage II or III disease; or stage I-III disease with serous or clear cell histology; were aged 18 years and older; and had a WHO performance status of 0-2. Participants were randomly assigned (1:1) to receive radiotherapy alone (48•6 Gy in 1•8 Gy fractions given on 5 days per week) or chemoradiotherapy (two cycles of cisplatin 50 mg/m² given intravenously during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m² given intravenously), by use of a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage, and histological type. The co-primary endpoints were overall survival and failure-free survival. Secondary endpoints of vaginal, pelvic, and distant recurrence were analysed according to the first site of recurrence. Survival endpoints were analysed by intention-to-treat, and adjusted for stratification factors. Competing risk methods were used for failure-free survival and recurrence. We did a post-hoc analysis to analyse patterns of recurrence with 1 additional year of follow-up. The study was closed on Dec 20, 2013; follow-up is ongoing. This study is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138.

Factors associated with survival after relapse in patients with low-risk endometrial cancer treated with surgery alone

Journal of gynecologic oncology, 2017

To determine factors influencing overall survival following recurrence (OSFR) in women with low-risk endometrial cancer (EC) treated with surgery alone. A multicenter, retrospective department database review was performed to identify patients with recurrent "low-risk EC" (patients having less than 50% myometrial invasion [MMI] with grade 1 or 2 endometrioid EC) at 10 gynecologic oncology centers in Turkey. Demographic, clinicopathological, and survival data were collected. We identified 67 patients who developed recurrence of their EC after initially being diagnosed and treated for low-risk EC. For the entire study cohort, the median time to recurrence (TTR) was 23 months (95% confidence interval [CI]=11.5-34.5; standard error [SE]=5.8) and the median OSFR was 59 months (95% CI=12.7-105.2; SE=23.5). We observed 32 (47.8%) isolated vaginal recurrences, 6 (9%) nodal failures, 19 (28.4%) peritoneal failures, and 10 (14.9%) hematogenous disseminations. Overall, 45 relapses (6...

Follow-up after primary therapy for endometrial cancer: A systematic review

Gynecologic Oncology, 2006

What is the most appropriate strategy for the follow-up of patients with endometrial cancer who are clinically disease free after receiving potentially curative primary treatment? Specifically, do differences in follow-up intervals, diagnostic interventions, clinical setting, or specialty influence patient outcomes related to local or distant recurrence, survival, or quality of life?

Radiotherapy and Chemotherapy Features in the Treatment for Locoregional Recurrence of Endometrial Cancer: A Systematic Review

Journal of Personalized Medicine

Radiation therapy (RT) is the standard of care in patients with locoregional or isolated vaginal recurrence who never underwent irradiation. It is often associated with brachytherapy (BT), whereas chemotherapy (CT) is a rare treatment option. We systematically searched the PubMed and Scopus databases in February 2023. We included patients with relapsed endometrial cancer, describing the treatment of locoregional recurrence, and reporting at least one outcome of interest—disease-free survival (DFS), overall survival (OS), recurrence rate (RR), site of recurrence, and major complications. A total of 15 studies fulfilled the inclusion criteria. Overall, 11 evaluated RT only, 3 evaluated CT, and 1 analyzed oncological outcomes after administration with a combination of CT and RT. In total, 4.5-year OS ranged from 16% to 96%, and DFS ranged from 36.3% to 100% at 4.5 years. RR ranged from 3.7% to 98.2% during a median follow-up of 51.5 months. Overall, RT showed a 4.5-year DFS from 40% to...

Significant pelvic recurrence in high-risk pathologic stage I–IV endometrial carcinoma patients after adjuvant chemotherapy alone: implications for adjuvant radiation therapy

International Journal of Radiation Oncology Biology Physics, 2001

Objective: To evaluate the risk of pelvic recurrence (PVR) in high-risk pathologic Stage I-IV endometrial carcinoma patients after adjuvant chemotherapy alone. Methods: Between 1992 and 1998, 43 high-risk endometrial cancer patients received adjuvant chemotherapy. All patients underwent primary surgery consisting of total abdominal hysterectomy and bilateral salpingo-oophorectomy. No patients received preoperative radiation therapy (RT). Regional lymph nodes and peritoneal cytology were sampled in 62.8% and 83.7% of cases, respectively. Most patients had Stage III-IV disease (83.7%) or unfavorable histology tumors (74.4%). None had evidence of extra-abdominal disease. All patients received 4 -6 cycles of chemotherapy as the sole adjuvant therapy, consisting primarily of cisplatin and doxorubicin. Recurrent disease sites were divided into pelvic (vaginal, nonvaginal) and extrapelvic (para-aortic, upper abdomen, liver, and extra-abdominal). Median follow-up was 27 months (range, 2-96 months). Results: Twenty-nine women (67.4%) relapsed. Seventeen (39.5%) recurred in the pelvis and 23 (55.5%) in extrapelvic sites. The 3-year actuarial PVR rate was 46.5%. The most significant factors correlated with PVR were cervical involvement (CI) (p ‫؍‬ 0.01) and adnexal (p ‫؍‬ 0.05) involvement. Of the 17 women who developed a PVR, 8 relapsed in the vagina, 3 in the nonvaginal pelvis, and 6 in both. The 3-year vaginal and nonvaginal PVR rates were 37.8% and 26%, respectively. The most significant factor correlated with vaginal PVR was CI (p ‫؍‬ 0.0007). Deep myometrial invasion (p ‫؍‬ 0.02) and lymph nodal involvement (p ‫؍‬ 0.03) were both correlated with nonvaginal PVR. Nine of the 29 relapsed patients (31%) developed PVR as their only (6) or first site (3) of recurrence. Factors associated with a higher rate of PVR (as the first or only site) were CI and Stage I-II disease. Conclusions: PVR is common in high-risk pathologic Stage I-IV endometrial cancer patients after adjuvant chemotherapy alone. These results support the continued use of locoregional RT in patients undergoing adjuvant chemotherapy. Further studies are needed to test the addition of chemotherapy to locoregional RT.

Vaginal vault recurrences of endometrial cancer in non-irradiated patients — Radiotherapy or surgery

Gynecologic Oncology Reports, 2015

Background: The treatment of locally recurrent endometrial cancer is based on limited evidence. The standard treatment is radiotherapy (RT) which is effective for local control and the effect has been documented in prospective studies. Investigations of surgical treatment (ST) of recurrences are few and limited to previously irradiated patients or patients with advanced disease. Investigation of surgical treatment for isolated vaginal vault recurrence is practically nonexistent. The aim of this study is to evaluate the efficacy of RT and ST in a nonirradiated group with recurrent endometrial cancer limited to the vaginal vault. Methods: Patients treated for recurrent endometrial cancer at Odense University Hospital, Denmark between 2003 and 2012 were identified, n = 118. Thirty-three patients had an isolated vaginal vault recurrence and were treated with either RT, ST or both. Re-recurrence rates and survival rates were calculated at 2 year follow-up using Fishers exact test. Results: Twenty-six patients were treated with RT, 5 with ST, 2 with both. The mean (SD) follow-up-time was 4.4 years (2.99) (RT) and 3.9 years (0.90) (ST). Two year re-recurrence rates were 40% (RT) (95 CI 9.2-48%) and 0% (ST) (95 CI 0-60%). Two-year survival rates were 83% (RT) (95 CI 71-100%) and 100% (ST) (95 CI 40-100%) ST had one re-recurrence at 2.3 years. Conclusion: This study indicates that ST is an appropriate treatment for locally recurrent endometrial cancer. Our study involves a limited number of patients and is made retrospectively, therefore prospective and ideally randomized trials evaluating both survival and complications are warranted.

Surgical treatment of recurrent endometrial carcinoma

Cancer, 2003

BACKGROUND. Surgery does not have a definite role in the treatment of patients with recurrent endometrial carcinoma, except for those with central pelvic recurrences. The authors describe their experience with surgery in patients with abdominal endometrial recurrences. METHODS. Between 1988 and 2000, 75 patients with abdominal and pelvic endometrial recurrences underwent secondary rescue surgery. Patients were classified according to the presence or absence of residual tumor after surgery. Therapy after rescue surgery was undertaken at the discretion of the medical oncologist. The progression-free interval and overall survival were defined as the time from secondary rescue surgery to the specific event and were evaluated by the Kaplan-Meier method and the log-rank test. A Cox proportional hazards regression model was used to compare survival with covariates. RESULTS. Fifty-six patients (74.7%) underwent optimal debulking. Major surgical complications were observed in 23 patients (30.7%). Only 1 postoperative death was observed, although the mortality rate for surgical complications after the postoperative period was 8%. Patients who underwent optimal debulking had a significantly better cumulative survival rate compared with patients who had residual disease (36% vs. 0% at 60 months; P Ͻ 0.05). Residual disease, chemotherapy after rescue surgery, and central pelvis-vagina as the only site of recurrence were associated significantly with survival. CONCLUSIONS. The authors found that this approach was very challenging in terms of the procedures involved, the incidence of major surgical complications, and the high mortality rate. It was useful in increasing overall survival, provided that patients were free of macroscopic disease. Careful selection of patients is needed to minimize mortality. Cancer 2004;100:89-96.