Recurrence and survival of patients with stage III endometrial cancer after radical surgery followed by adjuvant chemo- or chemoradiotherapy: a systematic review and meta-analysis

doi:10.21203/rs.3.rs-2002220/v1

Download PDF

Research Article

Recurrence and survival of patients with stage III endometrial cancer after radical surgery followed by adjuvant chemo- or chemoradiotherapy: a systematic review and meta-analysis

https://doi.org/10.21203/rs.3.rs-2002220/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 09 Jan, 2023

Read the published version in BMC Cancer →

You are reading this latest preprint version

Objective

To compare recurrence and survival in patients with stage III endometrial cancer after radical surgery, followed by either adjuvant chemoradiotherapy (ACR) or adjuvant chemotherapy (AC).

Methods

We searched for relevant studies in PubMed Central, Embase and the Cochrane Central Register of Controlled Trials. Data were pooled on rates of recurrence as well as rates of progression-free, disease-free and overall survival. Heterogeneity was evaluated using the I² test. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity.

Results

Data from 55,440 patients in 22 retrospective studies and one randomized controlled trial were meta-analyzed. Compared to the AC group, the ACR showed significantly lower risk of local recurrence (OR 0.43, 95%CI 0.31–0.58) and total recurrence (OR 0.71, 95%CI 0.58–0.87). ACR was also associated with significantly better overall survival (HR 0.68, 95%CI 0.63–0.74), progression-free survival (HR 0.54, 95%CI:0.38–0.77) and disease-free survival (HR 0.54, 95%CI 0.30–0.96).

Conclusions

Adding adjuvant radiotherapy to adjuvant chemotherapy after radical surgery may significantly reduce risk of local and overall recurrence, while significantly improving survival of patients with stage III endometrial cancer.

Endometrial cancer

Chemotherapy

Radiotherapy

Chemoradiotherapy

Meta-Analysis

Endometrial cancer is one of the most frequent malignancies in the female reproductive system, and the morbidity and mortality associated with the disease continue to rise ^{[1, 2]}, including in developed countries ^[3]. Worldwide in 2021, 604,127 new cases were reported, and approximately 341,831 patients died ^[4]. The 5-year overall survival (OS) with endometrial cancer can be as high as 80%, making prognosis better than with ovarian or cervical cancer ^[1]. However, the rate of 5-year OS is lower than 20% for patients with advanced or recurrent endometrial cancer ^[5].

Based on the most widely used endometrial cancer staging system, from the International Federation of Gynecology and Obstetrics (FIGO) ^[6], stage III endometrial cancer can involve the uterine serosa and/or adnexa (substage IIIA), vagina or parametrium (IIIB), or pelvic or para-aorta lymph node (IIIC). The usually therapy for stage III patients is radical surgery involving total hysterectomy and bilateral salpingo-oophorectomy (TH/BSO), sometimes also with pelvic or para-aortic lymph node dissection^{[7, 8]}.

The National Comprehensive Cancer Network (NCCN) recommends adjuvant therapies after radical surgery, which can involve chemo- and radiotherapy, on their own or combined ^[8]. On its own, adjuvant chemotherapy (AC) can significantly improve survival^[9], but it does not appear to decrease the rate of distant recurrence. On its own, radiotherapy of the pelvic area or entire abdominal area can reduce the rate of pelvic recurrence but not the rate of distant recurrence, limiting long-term survival benefit ^[10–12].

Combining the two therapies into adjuvant chemoradiotherapy (ACR) may make up for the shortcomings of each therapy on its own^[13]. However, whether ACR is associated with better prognosis than AC is unclear: some studies have reported significantly better progression-free and overall survival with ACR ^{[14, 15]}, whereas others have found no difference between AC and ACR in recurrence-free survival among patients with endometrial cancer in stages III-IVA ^{[12, 16, 17]}. Large randomized trials are currently comparing ACR and AC for patients with stage III disease ^{[18, 19]}, but the data are not yet mature for analysis.

Therefore we undertook the present study to assess the available evidence on whether ACR provides benefits over AC in the treatment of stage III endometrial cancer patients after primary radical surgery.

This meta-analysis was performed in strict accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, and it was registered with the International Prospective Register of Systematic Reviews (CRD42022312042).

2.1 Literature search strategy

The databases in PubMed Central, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to March 1, 2022 for randomized controlled trials (RCTs), case control trials and cohort trials. The following search string was used for all fields: (endometrial neoplasm OR endometrial cancer OR endometrial carcinoma OR endometrium carcinoma OR endometrium neoplasm OR endometrium neoplasm) AND (postoperative OR hysterectomy OR surgical) AND (chemotherapy, adjuvant OR pharmacotherapy OR radiotherapy, adjuvant).

We also manually screened the reference lists of articles to identify additional articles. In cases of duplicate studies reporting on the same patient population, only the most complete publication was included. Two authors (SY Cao and Y Fan) independently searched all databases.

2.2 Study selection

To be included in the review and meta-analysis, studies had to satisfy the following inclusion criteria: (1) patients were diagnosed with endometrial carcinoma in FIGO stage III (regardless of whether the substage was A, B, or C), and they underwent primary surgery involving TH/BSO; (2) patients received AC or ACR after surgery; (3) the study design was randomized-controlled, observational prospective cohort, retrospective cohort or case-control; (4) relevant outcomes were reported, such as rates of recurrence and/or of progression-free survival (PFS), disease-free survival (DFS) and overall survival (OS); and (5) the full text of the study was available.

Studies were excluded if they (1) were not original research articles, such as reviews, study protocols, comments or letters; (2) were not published in English; (3) involved patients who received neoadjuvant therapy before surgery; (4) did not report necessary data; or (5) failed to score adequately in the quality assessment (see section 2.3)

2.3 Quality assessment

Two researchers (SY Cao and Y Fan) independently assessed the methodological quality of the included studies. We used the Newcastle-Ottawa Quality Assessment Scale (NOS) ^[20] to evaluate the quality of non-randomized studies, and the Jadad/Oxford quality scoring system^[21] to evaluate the quality of RCTs. Only non-randomized studies with total scores of at least five points or RCTs with total scores of at least three points were included in the final meta-analysis. Any disagreements were resolved by discussion with the corresponding author.

2.4 Data extraction

Two authors (SY Cao and Y Fan) independently extracted data from included studies. Extracted data included: first author, country or region, FIGO stage and substage, age of patients, year of publication, study name, number of patients enrolled, study type, type of AC, type of ACR, rate of recurrence (local, distant and total), PFS, DFS, OS, and median follow-up. Any disagreements were resolved by discussion with the corresponding author.

Patients were defined to have experienced recurrence if they initially achieved complete remission after AC or ACR, but subsequently suffered recurrent cancer anywhere in the body, based on histopathology or imaging^[8]. Relapse in the vaginal vault, vagina, pelvic cavity, pelvic and/or para-aortic nodes was considered local recurrence ^[17]; relapse at other sites was defined as distant recurrence^[16]. OS, DFS and PFS were extracted directly from the studies or from the published Kaplan-Meier plots. Any uncertainties about data extraction and classification were resolved by discussion with the corresponding author.

2.5 Data analysis

Statistical analyses were calculated using the metan, metabias and metaprop packages in STATA 16.0 (Statacorp, College Station, TX, USA). We calculated odds ratios (ORs) or hazard ratios (HRs) and the associated 95% confidence intervals (CIs). When the included studies did not directly report HR for OS or PFS, the necessary data were extracted using Engauge Digitizer 4.1 (http://sourceforge.net/projects/digitizer/).

Meta-analysis was initially conducted using a random-effects model, and the heterogeneity was assessed in terms of I², where I²≥ 50% was considered high heterogeneity^[22]. Potential sources of heterogeneity were explored by performing subgroup analysis based on FIGO substage (IIIA, IIIB or IIIC) or histological type (endometroid or non-endometroid carcinoma), and by repeating the meta-analysis after removing one study at a time. Publication bias was assessed using Begg's test^[23].

3.1 Characteristics of included studies

The results of the literature search and screening can be found in Fig. 1. A total of 3,571 articles were searched, which after careful screening led to a final set of 23 articles with 55,440 patients ^{[14–17, 24–41]}, of which 22 were retrospective cohort studies and one was a RCT. The studies were conducted in the United States (15), Italy (3), Taiwan (2), United Kingdom (1), Netherlands (1), or Eastern Europe and Central Africa (1). The characteristics and quality scores of the included articles are listed in Table 1.

Histological types of endometrial cancer in the studies included endometroid carcinoma and non-endometroid carcinoma. Non-endometroid types included carcinosarcoma, serous adenocarcinoma, clear cell adenocarcinoma and other types.

3.2 Quality assessment

Table 2 shows the quality assessment of retrospective studies. The quality of RCT was assessed based on five scores.

3.3 Recurrence rate

Seven articles ^{[12, 16, 27, 31, 32, 34, 38]} involving 1,966 patients reported recurrence rates for AC and ACR groups (Fig. 2A). Meta-analysis showed a total recurrence rate of 34.3% (256/745) for the AC group and 27.2% (333/1221) for the ACR group, corresponding to significantly lower risk of recurrence with ACR: OR 0.71, 95%CI 0.58–0.87 (I² = 26.3%, p = 0.228). Similarly, the rate of local recurrence was significantly lower in the ACR group (7.1% vs 16.0%, OR 0.43, 95%CI 031-0.58; I² = 35.6%, p = 0.157; Fig. 2B). In contrast, distant recurrence rate was similar between the ACR and AC groups (17.6% vs 16.1%, OR 1.20, 95%CI 093-1.55; I² = 29.1%, P = 0.217; Fig. 2C).

3.4. OS rate

Meta-analysis of data for 54,644 patients in 21 studies^{[14–17,24−33,35−41]} showed that ACR was associated with significantly better OS than AC (HR 0.68, 95%CI 0.63–0.74; I² = 74.5%, P < 0.001; Fig. 3).

Given the high heterogeneity of the pooled data, we conducted subgroup analyses. The significantly better OS with ACR than AC was observed in the subgroups of stage IIIA patients (HR 0.83, 95%CI 0.75–0.92, I² = 0.0%, P = 0.580)^{[15–17, 28, 30, 38]} and stage IIIC patients (HR 0.64, 95%CI 0.54–0.75, I² = 86.0%, P < 0.001)^{[14–16, 27, 28, 30, 32, 33, 37, 41]}. However, no significant OS difference was observed between ACR and AC among stage IIIB patients (HR 0.64, 95%CI 0.39–1.05; I² = 75.3%, P = 0.044)^{[15, 30]} (Fig. 4A).

Subgroup analysis showed that the significant OS benefit of ACR over AC was observed among the separate subgroups of patients with endometroid carcinoma (HR 0.79, 95%CI 0.69–0.89; I² = 58.9%, P = 0.017) and non-endometroid carcinoma (HR 0.79, 95%CI 0.72–0.85; I² = 0.0%, P = 0.629; Fig. 4B).

Sensitivity analysis in which each study was removed one by one did not identify obvious sources of heterogeneity.

3.5 Rates of PFS and DFS

Meta-analysis of PFS data for 350 patients in three studies ^{[14, 34, 41]} showed that ACR was associated with significantly better PFS than AC (HR 0.54, 95%CI 0.38–0.77; I² = 0.0%, P = 0.385; Fig. 5A). Similarly, meta-analysis of data for 1,000 patients in four studies ^{[16, 26, 27, 31]} showed that ACR was associated with significantly better DFS (HR 0.54, 95%CI 0.30–0.96; I² = 68.7, P = 0.012; Fig. 5B).

3.6 Publication bias

Publication bias was calculated for the meta-analysis of OS, which most studies reported ^{[14–17,24-33,35−41]}. Begg’s test suggested potential publication bias (p = 0.038), and the funnel chart showed an asymmetric distribution (Fig. 6).

In this meta-analysis of patients with FIGO stage III endometrial cancer who underwent radical surgery, we compared cancer recurrence rates and survival between those who received AC or ACR after surgery. The two adjuvant treatments were associated with similar distant recurrence, while ACR was associated with significantly lower risk of total recurrence and local recurrence. These outcomes were associated with low heterogeneity. ACR was also associated with significantly higher OS than AC, although this outcome was associated with high heterogeneity and we were unable to identify its sources.

The results from our meta-analysis are consistent with several previous studies. For example, analysis of data in the US National Cancer Data Base suggests better survival with ACR than AC ^{[18, 28, 42]}.

We found evidence of better survival with ACR than AC specifically in patients with endometrial cancer in stage IIIA or IIIC. These results suggest that ACR is more effective at preventing cancer recurrence and improving OS in the presence of pelvic lymph node involvement (substage IIIC1) or para-aortic lymph node metastasis (substage IIIC2).

We found evidence of better survival with ACR than AC specifically in patients with either endometroid or non-endometroid carcinoma. This is an important finding because the non-endometroid type is associated with worse prognosis. In this sense, our finding is consistent with reports that ACR provides overall survival benefit over AC for serous carcinoma, which is also associated with worse prognosis ^{[43, 44]}. This literature and our meta-analysis suggest that ACR may lead to better prognosis in patients with severe or advanced forms of endometrial cancer.

While our findings may differ from those in the large RCT GOG-258, some work suggests that this trial may underestimate the ability of ACR to reduce recurrence rate because the radiation dose in the combination regime may have been insufficient ^{[12, 18]}. Consistent with our meta-analysis, the multi-center PORTEC-3 trial showed that ACR led to better 5-year rates of DFS and OS than adjuvant radiotherapy alone, especially among patients with high-risk histological types of endometrial cancer^[45].

Our meta-analysis presents several limitations. First, pooled OS data showed high heterogeneity, the sources of which we were unable to identify. Nevertheless, our OS meta-analysis seems reliable because we obtained similar results in subgroup analyses, which involved fewer confounding factors. Second, we were unable to take into account factors that might affect survival, such as residual tumor volume after surgery, differences in chemo- or radiotherapy regimens, and lymph node dissection. Few studies reported data on such factors. Third, all but one study in our meta-analysis were retrospective studies, which may increase the risk of selection bias. In addition, the one RCT in our meta-analysis contained 22 patients in stages I, II or IV, whom we could not exclude. Fourth, the radiotherapy in the ACR regimen varied across the included studies (e.g. external pelvic radiotherapy, vaginal brachytherapy). This may have contributed to the observed heterogeneity. Fifth, we had to extract HRs from Kaplan-Meier plots in nearly half the studies^{[17, 26, 27, 30, 35, 38, 39, 41]}, which may have introduced error. Finally, we found evidence of publication bias toward greater clinical benefits of ACR than AC among the studies in our meta-analysis.

Despite these limitations, our meta-analysis provides strong evidence that ACR is superior to AC for preventing recurrence and improving survival of patients with stage III endometrial cancer. To the best of our best knowledge, this is the first meta-analysis to compare the two adjuvant approaches after primary radical surgery. Our findings suggest recommending ACR to patients with stage III disease, especially those at greater risk of recurrence.

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Availability of data and materials

The datasets during and/or analysed during the current study available from the corresponding author on reasonable request.

Disclosure of interests

The authors declare no conflicts of interest.

Funding

This study was supported by the Science & Technology Department of Sichuan Province, China (2017SZ0118, 2021YJ0124). The funder played no role in the study design; in the collection, analysis or interpretation of data; in the writing of the manuscript; or in the decision to submit it for publication.

Author contribution

Si-Yu Cao: Conceptualization, Writing - Original Draft, Methodology, Investigation, Formal analysis. Yu Fan: Investigation, Writing - Review & Editing. Yu-Fei Zhang: Data Curation. Jia-ying Ruan: Visualization. Yi Mu: Supervision. Jin-ke Li: Conceptualization, Writing - Review & Editing, Project administration.

Acknowledgements

I would first like to thank my tutor, Jin-ke Li, whose expertise was invaluable in formulating the research questions and methodology. I would particularly like to acknowledge my group mates and classmates, for their wonderful collaboration and patient support. Finally, we thank the associate editors and the reviewers for their useful feedback that improved this paper.

Lu K H, Broaddus R R. Endometrial Cancer[J]. New England Journal of Medcine, 2020, 383(21):2053–2064.
Jemal A, Ward E M, Johnson C J, et al. Annual Report to the Nation on the Status of Cancer, 1975–2014, Featuring Survival[J]. JNCI: Journal of the National Cancer Institute, 2017, 109(9):djx030.
Sheikh M A, Althouse A D, Freese K E, et al. USA Endometrial Cancer Projections to 2030: should we be concerned?[J]. Future Oncology, 2014, 10(16):2561–2568.
Global Cancer Observatory: Cancer Today (2021). International Agency for Research on Cancer. [EB/OL]. (November 18, 2021)[https://gco.iarc.fr/today.
Brooks R A, Fleming G F, Lastra R R, et al. Current recommendations and recent progress in endometrial cancer[J]. CA: A Cancer Journal for Clinicians, 2019, 69(4):258–279.
Bhatla N, Denny L. FIGO Cancer Report 2018[J]. International Journal of Gynecology & Obstetrics, 2018, 143(S2):2–3.
Crosbie E J, Kitson S J, Mcalpine J N, et al. Endometrial cancer[J]. The Lancet, 2022, 399(10333):1412–1428.
Abu-Rustum N R, Yashar C M, Bradley K, et al. NCCN Guidelines® Insights: Uterine Neoplasms, Version 3.2021.1540–1413.
Randall M E, Filiaci V L, Muss H, et al. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study[J]. Journal of Cancer Research and Clinical Oncology, 2006, 24(1):36–44.
Shaikh T, Churilla T M, Mantia-Smaldone G M, et al. The role of adjuvant radiation in lymph node positive endometrial adenocarcinoma[J]. Gynecologic Oncology, 2016, 141(3):434–439.
Mariani A, Dowdy S C, Cliby W A, et al. Efficacy of systematic lymphadenectomy and adjuvant radiotherapy in node-positive endometrial cancer patients[J]. Gynecologic Oncology, 2006, 101(2):200–8.
Matei D, Filiaci V, Randall M E, et al. Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer[J]. New England journal of medicine, 2019, 380(24):2317–2326.
Onal C, Sari S Y, Yildirim B A, et al. A multi-institutional analysis of sequential versus 'sandwich' adjuvant chemotherapy and radiotherapy for stage IIIC endometrial carcinoma[J]. Journal of Gynecologic Oncology, 2019, 30(3):e28.
Mceachron J, Marshall L, Zhou N, et al. Evaluation of Survival, Recurrence Patterns and Adjuvant Therapy in Surgically Staged High-Grade Endometrial Cancer with Retroperitoneal Metastases[J]. Cancers (Basel), 2021, 13(9):2052.
Kidd E A, Xiang M, English D P. Defining the survival benefit of adjuvant pelvic radiotherapy and chemotherapy versus chemotherapy alone in stages III-IVA endometrial carcinoma[J]. Gynecologic Oncology, 2019, 154(3):487–494.
Kahramanoglu I, Meydanli M M, Taranenka S, et al. SATEN III-Splitting Adjuvant Treatment of stage III ENdometrial cancers: an international, multicenter study[J]. International Journal of Gynecological Cancer, 2019, 29(8):1271–1279.
Montes De Oca M K, Albright B B, Secord A A, et al. Adjuvant treatment and outcomes for patients with stage IIIA grade 1 endometrioid endometrial cancer[J]. International Journal of Gynecological Cancer, 2021, 31(12):1549–1556.
Chapman B V, Swanick C W, Ning M S, et al. Adjuvant combined-modality therapy for stage IIIC endometrioid and non-endometrioid endometrial cancer[J]. Gynecologic Oncology, 2019, 154(1):22–28.
Ngu S-F, Ngan H Y S, Chan K K L. Role of adjuvant and post-surgical treatment in gynaecological cancer[J]. Best Practice and Research: Clinical Obstetrics and Gynaecology, 2021, 78:2–13.
Wells Ga, Shea B, O’connell D, et al. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Non-Randomized Studies in Meta-Analyses (2018). [EB/OL]. (April 23, 2022)[http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
Jadad Ar, Moore Ra, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? [J]. Controlled Clinical Trials, 1996, 17:1–12.
Jp. H, Sg. T, Jj. D, et al. Measuring Inconsistency in Meta-Analyses. [J]. British Medical Journal, 2003, 327(7414):557–60.
Cb. B, M. M. Operating Characteristics of a Rank Correlation Test for Publication Bias.[J]. Biometrics, 1994, 50:1088–101.
Albuquerque K, Folkert M, Mayadev J, et al. Adjuvant external radiation impacts outcome of pelvis-limited stage III endometrial carcinoma: A multi-institutional study[J]. American Journal of Clinical Oncology: Cancer Clinical Trials, 2018, 41(8):792–796.
Van Weelden W J, Reijnen C, Eggink F A, et al. Impact of different adjuvant treatment approaches on survival in stage III endometrial cancer: A population-based study[J]. European Journal of Cancer, 2020, 133:104–111.
Signorelli M, Lissoni A A, De Ponti E, et al. Adjuvant sequential chemo and radiotherapy improves the oncological outcome in high risk endometrial cancer[J]. Journal of Gynecologic Oncology, 2015, 26(4):284–92.
Bogani G, Cappuccio S, Casarin J, et al. Role of adjuvant therapy in stage IIIC2 endometrial cancer[J]. International Journal of Gynecological Cancer, 2020, 30(8):1169–1176.
Syeda S, Chen L, Hou J Y, et al. Chemotherapy, Radiation, or Combination Therapy for Stage III Uterine Cancer[J]. Obstetrics and Gynecology, 2019, 134(1):17–29.
Ko E M, Brensinger C M, Cory L, et al. Utilization and survival outcomes of sequential, concurrent and sandwich therapies for advanced stage endometrial cancers by histology[J]. Gynecologic Oncology, 2020, 159(2):394–401.
Lester-Coll N H, Park H S, Rutter C E, et al. Who benefits from chemoradiation in stage III-IVA endometrial cancer? An analysis of the National Cancer Data Base[J]. Gynecologic Oncology, 2016, 142(1):54–61.
Kuku S, Williams M, Mccormack M. Adjuvant therapy in stage III endometrial cancer: treatment outcomes and survival. a single-institution retrospective study[J]. International Journal of Gynecological Cancer, 2013, 23(6):1056–64.
Secord A A, Geller M A, Broadwater G, et al. A multicenter evaluation of adjuvant therapy in women with optimally resected stage IIIC endometrial cancer[J]. Gynecologic Oncology, 2013, 128(1):65–70.
Lin J F, Muñiz K, Sukumvanich P, et al. Survival advantage associated with multimodal therapy in women with node-positive (stage-IIIC) uterine papillary serous carcinoma: a National Cancer Database study[J]. British Journal of General Practice, 2016, 123(11):1846–52.
Marchetti C, Pisano C, Mangili G, et al. Use of adjuvant therapy in patients with FIGO stage III endometrial carcinoma: a multicenter retrospective study[J]. Oncology, 2011, 81(2):104–12.
Huang C-Y, Chen J L-Y, Hsu C-Y, et al. 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[J]. Radiation Oncology, 2020, 15(1):72.
Mahdi H, Rose P G, Nutter B, et al. The impact of combined radiation and chemotherapy on outcome in uterine papillary serous carcinoma compared to chemotherapy alone[J]. Journal of Gynecologic Oncology, 2016, 27(2):e19.
Lee J, Yu T, Tsai M H. Lymph Node Number Predicts the Efficacy of Adjuvant Chemoradiotherapy in Node-Positive Endometrial Cancer Patients[J]. Diagnostics (Basel), 2020, 10(6):373.
Havrilesky L J, Secord A A, O'malley D M, et al. Multicenter analysis of recurrence and survival in stage IIIA endometrial cancer[J]. Journal of Gynecologic Oncology, 2009, 114(2):279–83.
Verrengia A, Sigismondi C, Iannacone E, et al. Does cytoreductive surgery followed by adjuvant chemo-radiotherapy decrease the risk of recurrence and death in stage III endometrial cancer?[J]. Tumori Journal, 2020, 106(4):319–324.
Wang C J, Christie A, Folkert M R, et al. Value of combined adjuvant chemotherapy and radiation on survival for stage III uterine cancer: is less radiation equal to more?[J]. Journal of Gynecologic Oncology, 2018, 29(4):e49.
Binder P S, Kuroki L M, Zhao P, et al. Benefit of combination chemotherapy and radiation stratified by grade of stage IIIC endometrial cancer[J]. Gynecologic Oncology, 2017, 147(2):309–314.
Felix A S, Cohn D E, Brasky T M, et al. Receipt of adjuvant endometrial cancer treatment according to race: an NRG Oncology/Gynecologic Oncology Group 210 Study[J]. American Journal of Obstetrics and Gynecology, 2018, 219(5):459.e1-459.e11.
Jhingran A, Ramondetta L M, Bodurka D C, et al. A prospective phase II study of chemoradiation followed by adjuvant chemotherapy for FIGO stage I-IIIA (1988) uterine papillary serous carcinoma of the endometrium[J]. Gynecologic Oncology, 2013, 129(2):304-9.
Leon-Castillo A, De Boer S M, Powell M E, et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: Impact on prognosis and benefit from adjuvant therapy[J]. Journal of Clinical Oncology, 2020, 38(29):3388–3397.
De Boer S M, Powell M E, Mileshkin L, et al. 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[J]. Lancet Oncology, 2019, 20(9):1273–1285.

Tables 1 and 2 are available in the Supplementary Files section.

No competing interests reported.

table1.xls
Table 1. Characteristics of included studies.
table2.xls
Table 2. Quality of retrospective studies, as assessed on the Newcastle-Ottawa Quality Assessment Scale (NOS).

Download PDF

Journal Publication

published 09 Jan, 2023

Read the published version in BMC Cancer →

Editorial decision: Major revision
24 Nov, 2022
Reviews received at journal
14 Nov, 2022
Reviewers agreed at journal
30 Oct, 2022
Reviews received at journal
24 Oct, 2022
Reviewers agreed at journal
20 Oct, 2022
Reviewers agreed at journal
17 Oct, 2022
Reviewers invited by journal
16 Oct, 2022
Editor assigned by journal
13 Oct, 2022
Editor invited by journal
05 Sep, 2022
Submission checks completed at journal
05 Sep, 2022
First submitted to journal
26 Aug, 2022

You are reading this latest preprint version

Recurrence and survival of patients with stage III endometrial cancer after radical surgery followed by adjuvant chemo- or chemoradiotherapy: a systematic review and meta-analysis

Status:

Journal Publication

Version 1

Abstract

Objective

Methods

Results

Conclusions

Figures

1. Introduction

2. Materials And Method

2.1 Literature search strategy

2.2 Study selection

2.3 Quality assessment

2.4 Data extraction

2.5 Data analysis

3. Results

3.1 Characteristics of included studies

3.2 Quality assessment

3.3 Recurrence rate

3.4. OS rate

3.5 Rates of PFS and DFS

3.6 Publication bias

4. Discussion

Declarations

References

tables

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1