Chemo-radiotherapy after neoadjuvant chemotherapy and radical hysterectomy in women with stage IB-IIB cervical cancer: Do we need to change the therapeutic approach? a cohort study

Chemo-radiotherapy after neoadjuvant chemotherapy and radical hysterectomy in women with stage IB-IIB cervical cancer: Do we need to change the therapeutic approach? a cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Chemo-radiotherapy after neoadjuvant chemotherapy and radical hysterectomy in women with stage IB-IIB cervical cancer: Do we need to change the therapeutic approach? a cohort study Somayeh Nikfar, Azam Sadat Mousavi, Setareh Akhavan, Shahrzad Sheikhhasani, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4392903/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Chemo-radiotherapy is recommended as the standard treatment for advanced cervical cancer, and neoadjuvant chemotherapy (NACT) can be beneficial for patients on long radiotherapy waiting lists. In this study, we aimed to evaluate the need for chemo-radiotherapy after NACT and radical hysterectomy in women with stage IB-IIB cervical cancer. Methods: This study is a retrospective cohort study. All patients of gynecologic oncology clinic of Imam Khomeini Hospital, Tehran, Iran who were diagnosed with stage IB-IIB cervical cancer and were treated with NACT and radical hysterectomy between 2010 and 2020, were included in this study. The records of all patients who met the inclusion criteria were evaluated during the study period. The interested outcomes and progression-free survival (PFS) were assessed. Results: In this study, clinical files of 613 patients with cervical cancer were studied and among them, 63 patients (10.2% of patients) underwent NACT. Eighteen patients (33.3%) did not require another treatment modality after chemotherapy and radical hysterectomy, while 66.7% (36 cases) of patients needed chemo-radiotherapy after NACT and radical hysterectomy, and recurrence was observed in 11.6% (5 cases) of patients. The 1-, 5- and 10-year PFS rate was 97.6% (95% CI: 84.2-99.6), 89.5% (95% CI: 74.4-95.9) and 89.5% (95% CI: 74.4-95.9), respectively. Conclusions: It can be concluded that a significant percentage of patients who are candidates for NACT followed by radical hysterectomy, would require another modality of treatment, which is chemo-radiotherapy; therefore, it is recommended that by conducting prospective studies, in addition to investigating this issue, the choice of the first method of patients treatment in these stages should be reconsidered so that the patient does not suffer from two treatments and related complications, and patients undergo chemo-radiotherapy from the beginning. Chemo-Radiotherapy Neoadjuvant Chemotherapy Radical Hysterectomy Cervical Cancer Progression-Free Survival Figures Figure 1 Introduction Cervical cancer is the second leading cause of cancer in less developed countries and the third leading cause of cancer in women worldwide. Unfortunately, the majority of patients with cervical cancer in developing countries are referred in advanced stages [ 1 , 2 ]. Treatment of cervical cancer can be done by surgery or radiotherapy with or without chemotherapy, depending on the size of the lesion, stage of the disease, histologic features, lymph node involvement, risk factors for surgery or radiotherapy, and the patient's preferred treatment [ 3 ]. Chemoradiotherapy is recommended as the standard treatment for advanced cervical cancer, while radiotherapy facilities are not available in developing countries, and neoadjuvant chemotherapy can be beneficial for patients on long radiotherapy waiting lists [ 4 , 5 ] . There is currently no conclusive evidence for the use of this therapeutic approach and further studies are needed. Numerous studies have shown that neoadjuvant chemotherapy is effective in reducing tumor size and eliminating micro-metastases and the possibility of surgery and reducing the disease stage in surgery [ 6 ]. It is estimated that more than 38% of cervical cancers are diagnosed in stage IB2-IIB. However, the treatment strategy for stage IB2-IIB, and especially stage IIB is controversial and although most patients with stage IB2-IIB cervical cancer initially respond to conventional therapy, which is concomitant chemotherapy based on Cisplatin and external radiotherapy followed by brachytherapy (CCRT), but 22% -41% of patients still have a recurrence [ 7 – 10 ]. In addition, this treatment is associated with early and long-term toxicities, including radiation cystitis, radiation-induced enterocolitis, vaginal stenosis, and pelvic adhesions. Therefore, physicians have been actively considering more effective treatments. Neoadjuvant chemotherapy (NACT) followed by radical surgery (hysterectomy plus pelvic lymph node dissection) (NACT + S) is the most researched treatment method and has attracted the most attention because, in addition to disease control, it has less toxicity [ 11 ]. Many studies have shown that NACT + S can reduce tumor size, improve R0 resection, reduce the risk of intraoperative spread, reduce the incidence of postoperative complications, and even improve the survival outcomes in comparison with surgery or radiation therapy. However, this therapeutic method also has disadvantages, such as prolonged treatment, increased medical costs, and potential tumor progression due to insensitivity to chemotherapy. In addition, some studies demonstrated that NACT + S has no benefit for survival. Therefore, there is still controversy about NACT + S treatment [ 4 , 12 – 16 ]. Treatment of cervical cancer can affect all aspects of a woman's life, including her physical and mental functioning. One of the most important activities that change during cervical cancer and radiotherapy is women's sexual function. The results of some studies in this field have shown that both surgical and radiotherapy methods have harmful and at the same time different effects on body function, especially female sexual function. Further studies have raised the question of which treatment method is better for patients with cervical cancer stage IIB-IB2 [ 17 – 19 ]. Also, paying attention to increasing the quality of life of patients in addition to increasing survival in patients with cervical cancer is a highly important issue. Therefore, in this study, we aimed to evaluate the need for chemo-radiotherapy after neoadjuvant chemotherapy and radical hysterectomy in women with stage IB-IIB cervical cancer to prevent the imposition of both treatments on patients. Materials and methods Study design The present research was a retrospective cohort study. All patients of gynecologic oncology clinic of Imam Khomeini Hospital who were diagnosed with stage IB-IIB cervical cancer and were treated with NACT and radical hysterectomy between 2010 and 2020, were included in this study. The records of all patients with cervical cancer who met the inclusion criteria were evaluated during the mentioned period. Ethical considerations For this study, all ethical codes related to human studies were considered. Patient information was kept confidential and published in groups. Also, the collected information of patients was anonymous and in cases where patients were contacted by phone, questions were asked if they wished to participate in the study. Also, this study has been approved by the ethics committee of Tehran University of Medical Sciences with the ethics code of IR.TUMS.IKHC.REC.1399.382. Inclusion and exclusion criteria Inclusion criteria comprised all patients diagnosed with primary cervical cancer stage IB-IIB, patients treated with neoadjuvant chemotherapy and radical hysterectomy, and availability of the patient's clinical records. Exclusion criteria comprised incompleteness of the data recorded in the file and incompletion of the treatment period before the start of the study. Study procedure The files of the patients with cervical cancer who were referred to the oncology clinic were reviewed in the desired period and the files of eligible patients were retrospectively studied and the required data, including patient age, parity, disease stage, type of neoadjuvant chemotherapy regimen used along with the dates of start and end, and postoperative pathology, were extracted from the files based on a questionnaire designed by the researcher. In addition, progression-free survival was evaluated. In cases where necessary, the telephone number in the patient's file was used to complete the data, and people were contacted. In cases where the patients' information was incomplete, this information was considered as missing data and other information of that patient were used in other analyzes. Outcomes studied in this research included recurrence, recurrence time, recurrence treatment, chemoradiotherapy sessions, and progression-free survival, which were collected from patients' records or by telephone calls. The required information was collected using a checklist designed by the researcher. The recurrence of the disease was evaluated based on the clinical symptoms and results of imaging. Progression-free survival was also evaluated based on how long the patient survived after the initial treatment of the disease without any signs or symptoms of the disease. Due to the nature of the study, all cases of cervical cancer that met the inclusion criteria were included in the study over a period of 10 years. It should be noted that this hospital is considered the referral center for cancer in Iran. Statistical analyzes Mean (standard deviation) and frequency (percentage) were used to describe quantitative and qualitative data, respectively. To evaluate the progression-free survival (PFS), the Kaplan-Meier method were used and the survival rate was reported by survival curve. All analyzes were performed using Stata software version 13 (Stata Corp, College Station, TX, USA). Results In this study, clinical files of 613 patients with cervical cancer referred to the oncology clinic of Imam Khomeini Hospital in Tehran during 2010 to 2020 were studied and among them, 63 patients (10.2% of patients) underwent NACT and by considering the reports and inclusion criteria, 48 patients (76.1% of NACT recipients) were included in the study, all of whom underwent NACT and radical hysterectomy. Of the remaining 15 patients, the date of the surgery was unknown in 6 patients and due to the lack of follow-up, the need for chemoradiotherapy was unknown in these cases. In two patients, radical surgery could not be performed due to severe intra-abdominal adhesions and these patients were considered as candidates for chemoradiotherapy alone. In addition to the NACT regimen, 4 patients received radiotherapy and then underwent radical hysterectomy, one of whom underwent brachytherapy after surgery and one received radiotherapy up to the para-aortic region; The other two, were not suitable candidates for radical hysterectomy after receiving NACT and as a result, were candidates for chemoradiotherapy. One of them became a candidate for total hysterectomy after completing radiotherapy due to the presence of atypical cells in the cervix. In 63 cases that were included in the initial analysis, the mean age of patients was 45.22 years (standard deviation 9.9 years). The mean gravidity of patients was 4.11 (with a standard deviation of 2.6). Regarding the stage of the disease at the time of diagnosis, 27 cases (44.3%) were in stage Ib2, 13 cases (21.3%) were in stage IIb, and 8 cases (13.1%) were in stage IIa. In terms of the NACT regimen, all patients were treated with the taxol and cisplatin regimens and 4 cases (6.3%) underwent radiotherapy in addition to chemotherapy. In 59 patients (95.2%), 3 NACT courses were used. 45 cases (90%) were squamous cell carcinoma (SCC) and 5 cases (10%) were adenocarcinoma. Regarding lymphovascular space invasion, 25 cases (53.2%) were negative and 22 patients (46.8%) were positive (Table 1 ). Tumor invasion depth was less than 50% in 25.5% (12 patients) and more than 50% in 53.2% (25 patients) and was also negative in 21.3% (10 patients). In terms of margin, lymph node, lower segment and parameter involvement, 44 patients (93.6%), 40 patients (85.11%), 43 patients (91.5%) and 46 patients (97.9%) were negative, respectively. Pathology risk of patients was also assessed and the results showed that this risk was high in 8 patients, moderate in 20 patients and low in 18 patients. Follow-up of patients showed that only 18 patients (33.3%) did not require another treatment modality after chemotherapy and radical hysterectomy, while 66.7% (36 cases) of patients needed chemoradiotherapy after neoadjuvant chemotherapy and radical hysterectomy. Patients were also evaluated for recurrence, of which 88.4% had no recurrence, while recurrence was observed in 11.6% (5 cases) of patients. Table 1 Frequency distribution of demographic and clinical variables in patients diagnosed with stage IB-IIB cervical cancer treated with NACT and radical hysterectomy Variables N (%) Age Mean (S.D.) 45.22 (9.7) Gravidity Mean (S.D.) 4.11 (2.6) Stage 1B2 27 (44.26) 1A2 1 (1.64) 1B 3 (4.92) 1B3 4 (6.56) 2A 8 (13.11) 2B 13 (21.31) 2A2 4 (6.56) 2A1 1 (1.64) NACT T + cis 59 (93.6) T + cis + rad 4 (6.4) NACT courses 1 1 (1.61) 2 1 (1.61) 3 59 (95.2) 4 1 (1.61) Primary pathology Adenocarcinoma 5 (10.0) SCC 45 (90.0) LVSI Negative 25 (53.2) Positive 22 (46.8) Depth 50% 25 (53.2) Negative 10 (21.3) Marg Negative 44 (93.6) Positive 3 (6.4) LN Negative 40 (85.1) Positive 7 (14.9) Lower Seg Negative 43 (92.5) Positive 4 (8.5) Parameter Negative 46 (97.9) Positive 1 (2.1) Pathology risk High 8 (17.4) Moderate 20 (43.5) Low 18 (39.1) Chemo-radiotherapy No 18 (33.3) Yes 36 (66.7) Recurrence No 38 (88.4) Yes 5 (11.6) Figure 1 shows the results of the Progression-Free Survival (PFS) analysis. According to this Figure, the PFS rate after one year was 97.6% (95% CI: 84.2–99.6), two-year PFS was 89.5% (95% CI: 74.4–95.9), 5-year PFS was 89.5% (95% CI: 74.4–95.9) and 10-year PFS were 89.5% (95% CI: 74.4–95.9). Discussion Of 48 patients who underwent NACT and radical hysterectomy, 29 (60.4% of patients) required chemoradiotherapy and 19 (39.6% of patients) did not require further treatment. The need for chemoradiotherapy in stage IIA, IB, and IIB were 33.3%, 66.67%, and 75%, respectively (p = 0.28). Although the differences observed in the study population were not statistically significant, this difference could be clinically significant and may indicate a possible association between the disease stage and the need for chemoradiotherapy, which should be investigated in larger studies. The mean overall survival (OS) and progression-free survival (PFS) in the studied patients were 52.8 months (40.9–64.7, CI:95%) and 51.1 months (39.3–62.9, CI:95%), respectively. The recurrence rate in the study population was 10.5% (5 patients). The postoperative pathology demonstrated that 4 of them were in the high-risk group and underwent chemoradiotherapy, and the remaining patient was in the intermediate-risk group. After surgery, she applied for radiotherapy, but only received external radiotherapy and did not undergo brachytherapy, which highlights the importance of brachytherapy in preventing recurrence of cervical cancer. Of the cases studied, 3 died (6.2%), all of which occurred in the recurrence group. 24 months after chemoradiotherapy, recurrence with bone metastasis was observed in one patient who was referred for chemotherapy and died 24 months after recurrence (OS = 48 months); The second patient, considering the pathology after surgery, was a candidate for chemoradiotherapy who refused to receive treatment, and after 9 months, metastasis to the bladder was observed and the patients died after 2 months (OS = 11 months); The third patient underwent chemoradiotherapy after surgery but did not receive brachytherapy and died 8 months after completing radiotherapy with bone metastasis. The mean PFS of patients with recurrence was 17.5 months (95% CI, 7–28 months) and their OS was 25.6 months (95% CI, 3.8–46.8 months). Nama et al. [ 20 ] conducted a non-randomized study in 2018 to evaluate the increase in morbidity due to surgery with NACT compared to primary chemoradiotherapy in patients with IB2 stage cervical cancer, and compared the results of surgery and chemoradiotherapy; they found that the data were similar for patients with stage IB2 and IIA, therefore, they concluded that to date there is no conclusive evidence for a preferred treatment option for stage IB2 cervical cancer. The findings of the present study showed that both treatment failure and recurrence occurred in the first two years after treatment and after two years, the PFS rate remained 89.5% until the end of the study (end of 10 years). In a meta-analysis study published by Ye et al. [ 21 ] in 2020, it was concluded that the short-term therapeutic effects of both treatment options were similar in patients with IB2-IIB stages of cervical cancer but the long-term effects of NACT along with surgery on OS and DFS were better in comparison with radiotherapy alone or CCRT; However, the limitations of this meta-analysis included the relatively small number of articles reviewed (5 articles), reviewing only survival rates and complications, and not reviewing the quality of life. A meta-analysis by Cheng et al. [ 22 ] found that CCRT in patients with IB2 / IIA2 stage cervical cancer was probably the best way to improve clinical outcomes, and suggested that phase III randomized trials be performed to assess this matter. Also, Lee et al. conducted a study [ 23 ] and compared 85 patients with IB-IIB cervical cancer treated with NACT + S and 358 patients receiving CCRT; the authors concluded that in patients with IB-IIB cervical cancer, NACT treatment with surgery has no therapeutic advantage over CCRT. Conclusion According to the results of this study, it can be stated that a significant percentage of patients with stage IIA and IIB cervical cancer who are candidates for NACT followed by radical hysterectomy, would require another modality of treatment, which is chemoradiotherapy; therefore, it is recommended that by conducting prospective studies, in addition to investigating this issue, the choice of the first method of treatment of patients in these stages should be reconsidered so that the patient does not suffer from two treatments and related complications, and patients with these stages undergo chemoradiotherapy from the beginning. This theory requires a comparative study of overall survival, PFS, and quality of life after treatment between the patients receiving chemoradiotherapy and those receiving NACT and radical hysterectomy and subsequent chemoradiotherapy. Abbreviations NACT Neoadjuvant chemotherapy S Surgery CCRT Adjuvant concurrent Chemoradiation therapy PFS Progression-free survival CI Confidence interval Declarations Ethics approval and consent to participate: This study was conducted in accordance with the Helsinki Declaration and was approved by the Tehran University of Medical Sciences ethics committee (Code: IR.TUMS.IKHC.REC.1399.382). Consent for publication: All the patients signed the informed consent form. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request Availability of data and materials: All data generated or analysed during this study are available for review by the Editor-in-Chief of this journal on request. Competing interests: The authors declare that they have no conflicts of interests. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflicts of Interest: The authors declare that they have no conflicts of interests. Authors' contributions: S.N. : interpretation of data, writing and editing the article AS.M.: Study conception and design S.A.: collecting data SH.SH.: collecting data A.AH. : data analysis R.P. : data analysis, interpretation of data N.Z. : Editing the final manuscript, corresponding Acknowledgements: We would like to thank the vice chancellor for the research of Tehran University of Medical Sciences and Imam Khomeini Hospital staffs for their supports. All authors have read and approved the manuscript References Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. 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BMC Cancer. 2021;21:1078. doi: 10.1186/s12885-021-08685-9. Lee J, Kim TH, Kim GE, Keum KC, Kim YB. Neoadjuvant chemotherapy followed by surgery has no therapeutic advantages over concurrent chemoradiotherapy in International Federation of Gynecology and Obstetrics stage IB-IIB cervical cancer. J Gynecol Oncol. 2016;27:e52. doi: 10.3802/jgo.2016.27.e52. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4392903","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":304759751,"identity":"bc7236df-aebd-44ca-872d-b1cec38acc35","order_by":0,"name":"Somayeh Nikfar","email":"","orcid":"","institution":"Department of Obstetrics and Gynecology, Taleghani Hospital, Arak University of Medical Sciences, Arak, Iran","correspondingAuthor":false,"prefix":"","firstName":"Somayeh","middleName":"","lastName":"Nikfar","suffix":""},{"id":304759752,"identity":"a68f9e64-9dbc-4a27-9e91-dfc0c5e7acd3","order_by":1,"name":"Azam Sadat 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Iran","correspondingAuthor":false,"prefix":"","firstName":"Shahrzad","middleName":"","lastName":"Sheikhhasani","suffix":""},{"id":304759755,"identity":"37787fe9-24ec-4396-8476-4abca52e96c9","order_by":4,"name":"Amir Almasi-Hashiani","email":"","orcid":"","institution":"Department of Epidemiology, Arak University of Medical Sciences, Arak, Iran","correspondingAuthor":false,"prefix":"","firstName":"Amir","middleName":"","lastName":"Almasi-Hashiani","suffix":""},{"id":304759756,"identity":"9dd865ad-514a-4804-a35d-ef40368894bd","order_by":5,"name":"Ramin Parvizrad","email":"","orcid":"","institution":"Department of Emergency Medicine, Arak University of Medical Sciences, Vali-Asr Hospital, Arak, Iran","correspondingAuthor":false,"prefix":"","firstName":"Ramin","middleName":"","lastName":"Parvizrad","suffix":""},{"id":304759757,"identity":"2fe6a6f5-fac5-45da-9081-2db7f0883e45","order_by":6,"name":"Narges Zamani","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFElEQVRIiWNgGAWjYDCCA2h8Hn4QmVBAihbJBpAWAxK0MBiARfBo4bt9gO3Bzz21cvIN7A8/3ai5I2N8fnXihwcGDPL8YhjGgYHkuQR2w55nx42BhidL5xx7xmN24+1mCaDDDGfOTsCqxeAMA5sEz4FjiRuAbpTOYTsM1HJ2A0hLgsFt3Fok/xw4Vj+/gbH5d86/wzzGM85u/kFIizTPgZoEhgPMbNK5bYd5DPh7t+G1RfIMY5u0zIEDhhsOs7FZ5/Yd5pG4wbvNIsFAAqdf+M4wH5N8c6BOXr69/fHtnG+H7fn7z26++aPCRp5fGrsWBgbGBiBxmIGBGSYgAVYpgUM5HNQhsfkPEFI9CkbBKBgFIwwAANAeYIvqs2AwAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Oncologic Gynecology, Vali-Asr Hospital, Imam Khomeini Hospital Complex (IKHC) Tehran University of Medical Sciences, Tehran, Iran","correspondingAuthor":true,"prefix":"","firstName":"Narges","middleName":"","lastName":"Zamani","suffix":""}],"badges":[],"createdAt":"2024-05-09 06:03:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4392903/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4392903/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57290576,"identity":"27d6b115-0c6a-40c6-a5b0-1098ee04ee03","added_by":"auto","created_at":"2024-05-28 17:57:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":22988,"visible":true,"origin":"","legend":"\u003cp\u003e10-year progression-free survival (PFS) in patients diagnosed with stage IB-IIB cervical cancer treated with NACT and radical hysterectomy\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4392903/v1/0e9a3ded8d65b7e5825d5594.png"},{"id":62397072,"identity":"38843dd0-2a94-4bac-859b-45803eaaaf57","added_by":"auto","created_at":"2024-08-13 17:32:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":395419,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4392903/v1/4825e2f4-6bcf-4072-b1fe-5661e9975593.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Chemo-radiotherapy after neoadjuvant chemotherapy and radical hysterectomy in women with stage IB-IIB cervical cancer: Do we need to change the therapeutic approach? a cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCervical cancer is the second leading cause of cancer in less developed countries and the third leading cause of cancer in women worldwide. Unfortunately, the majority of patients with cervical cancer in developing countries are referred in advanced stages [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Treatment of cervical cancer can be done by surgery or radiotherapy with or without chemotherapy, depending on the size of the lesion, stage of the disease, histologic features, lymph node involvement, risk factors for surgery or radiotherapy, and the patient's preferred treatment [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Chemoradiotherapy is recommended as the standard treatment for advanced cervical cancer, while radiotherapy facilities are not available in developing countries, and neoadjuvant chemotherapy can be beneficial for patients on long radiotherapy waiting lists [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] .\u003c/p\u003e \u003cp\u003eThere is currently no conclusive evidence for the use of this therapeutic approach and further studies are needed. Numerous studies have shown that neoadjuvant chemotherapy is effective in reducing tumor size and eliminating micro-metastases and the possibility of surgery and reducing the disease stage in surgery [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. It is estimated that more than 38% of cervical cancers are diagnosed in stage IB2-IIB. However, the treatment strategy for stage IB2-IIB, and especially stage IIB is controversial and although most patients with stage IB2-IIB cervical cancer initially respond to conventional therapy, which is concomitant chemotherapy based on Cisplatin and external radiotherapy followed by brachytherapy (CCRT), but 22% -41% of patients still have a recurrence [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition, this treatment is associated with early and long-term toxicities, including radiation cystitis, radiation-induced enterocolitis, vaginal stenosis, and pelvic adhesions. Therefore, physicians have been actively considering more effective treatments. Neoadjuvant chemotherapy (NACT) followed by radical surgery (hysterectomy plus pelvic lymph node dissection) (NACT\u0026thinsp;+\u0026thinsp;S) is the most researched treatment method and has attracted the most attention because, in addition to disease control, it has less toxicity [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Many studies have shown that NACT\u0026thinsp;+\u0026thinsp;S can reduce tumor size, improve R0 resection, reduce the risk of intraoperative spread, reduce the incidence of postoperative complications, and even improve the survival outcomes in comparison with surgery or radiation therapy. However, this therapeutic method also has disadvantages, such as prolonged treatment, increased medical costs, and potential tumor progression due to insensitivity to chemotherapy. In addition, some studies demonstrated that NACT\u0026thinsp;+\u0026thinsp;S has no benefit for survival. Therefore, there is still controversy about NACT\u0026thinsp;+\u0026thinsp;S treatment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR13 CR14 CR15\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTreatment of cervical cancer can affect all aspects of a woman's life, including her physical and mental functioning. One of the most important activities that change during cervical cancer and radiotherapy is women's sexual function. The results of some studies in this field have shown that both surgical and radiotherapy methods have harmful and at the same time different effects on body function, especially female sexual function. Further studies have raised the question of which treatment method is better for patients with cervical cancer stage IIB-IB2 [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Also, paying attention to increasing the quality of life of patients in addition to increasing survival in patients with cervical cancer is a highly important issue. Therefore, in this study, we aimed to evaluate the need for chemo-radiotherapy after neoadjuvant chemotherapy and radical hysterectomy in women with stage IB-IIB cervical cancer to prevent the imposition of both treatments on patients.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e \u003cstrong\u003eStudy design\u003c/strong\u003e \u003cp\u003eThe present research was a retrospective cohort study. All patients of gynecologic oncology clinic of Imam Khomeini Hospital who were diagnosed with stage IB-IIB cervical cancer and were treated with NACT and radical hysterectomy between 2010 and 2020, were included in this study. The records of all patients with cervical cancer who met the inclusion criteria were evaluated during the mentioned period.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthical considerations\u003c/strong\u003e \u003cp\u003e For this study, all ethical codes related to human studies were considered. Patient information was kept confidential and published in groups. Also, the collected information of patients was anonymous and in cases where patients were contacted by phone, questions were asked if they wished to participate in the study. Also, this study has been approved by the ethics committee of Tehran University of Medical Sciences with the ethics code of IR.TUMS.IKHC.REC.1399.382.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eInclusion and exclusion criteria\u003c/strong\u003e \u003cp\u003eInclusion criteria comprised all patients diagnosed with primary cervical cancer stage IB-IIB, patients treated with neoadjuvant chemotherapy and radical hysterectomy, and availability of the patient's clinical records. Exclusion criteria comprised incompleteness of the data recorded in the file and incompletion of the treatment period before the start of the study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eStudy procedure\u003c/strong\u003e \u003cp\u003eThe files of the patients with cervical cancer who were referred to the oncology clinic were reviewed in the desired period and the files of eligible patients were retrospectively studied and the required data, including patient age, parity, disease stage, type of neoadjuvant chemotherapy regimen used along with the dates of start and end, and postoperative pathology, were extracted from the files based on a questionnaire designed by the researcher. In addition, progression-free survival was evaluated. In cases where necessary, the telephone number in the patient's file was used to complete the data, and people were contacted. In cases where the patients' information was incomplete, this information was considered as missing data and other information of that patient were used in other analyzes.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eOutcomes studied in this research included recurrence, recurrence time, recurrence treatment, chemoradiotherapy sessions, and progression-free survival, which were collected from patients' records or by telephone calls. The required information was collected using a checklist designed by the researcher. The recurrence of the disease was evaluated based on the clinical symptoms and results of imaging. Progression-free survival was also evaluated based on how long the patient survived after the initial treatment of the disease without any signs or symptoms of the disease.\u003c/p\u003e \u003cp\u003eDue to the nature of the study, all cases of cervical cancer that met the inclusion criteria were included in the study over a period of 10 years. It should be noted that this hospital is considered the referral center for cancer in Iran.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eStatistical analyzes\u003c/strong\u003e \u003cp\u003eMean (standard deviation) and frequency (percentage) were used to describe quantitative and qualitative data, respectively. To evaluate the progression-free survival (PFS), the Kaplan-Meier method were used and the survival rate was reported by survival curve. All analyzes were performed using Stata software version 13 (Stata Corp, College Station, TX, USA).\u003c/p\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e In this study, clinical files of 613 patients with cervical cancer referred to the oncology clinic of Imam Khomeini Hospital in Tehran during 2010 to 2020 were studied and among them, 63 patients (10.2% of patients) underwent NACT and by considering the reports and inclusion criteria, 48 patients (76.1% of NACT recipients) were included in the study, all of whom underwent NACT and radical hysterectomy. Of the remaining 15 patients, the date of the surgery was unknown in 6 patients and due to the lack of follow-up, the need for chemoradiotherapy was unknown in these cases. In two patients, radical surgery could not be performed due to severe intra-abdominal adhesions and these patients were considered as candidates for chemoradiotherapy alone. In addition to the NACT regimen, 4 patients received radiotherapy and then underwent radical hysterectomy, one of whom underwent brachytherapy after surgery and one received radiotherapy up to the para-aortic region; The other two, were not suitable candidates for radical hysterectomy after receiving NACT and as a result, were candidates for chemoradiotherapy. One of them became a candidate for total hysterectomy after completing radiotherapy due to the presence of atypical cells in the cervix.\u003c/p\u003e \u003cp\u003eIn 63 cases that were included in the initial analysis, the mean age of patients was 45.22 years (standard deviation 9.9 years). The mean gravidity of patients was 4.11 (with a standard deviation of 2.6). Regarding the stage of the disease at the time of diagnosis, 27 cases (44.3%) were in stage Ib2, 13 cases (21.3%) were in stage IIb, and 8 cases (13.1%) were in stage IIa. In terms of the NACT regimen, all patients were treated with the taxol and cisplatin regimens and 4 cases (6.3%) underwent radiotherapy in addition to chemotherapy. In 59 patients (95.2%), 3 NACT courses were used. 45 cases (90%) were squamous cell carcinoma (SCC) and 5 cases (10%) were adenocarcinoma. Regarding lymphovascular space invasion, 25 cases (53.2%) were negative and 22 patients (46.8%) were positive (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Tumor invasion depth was less than 50% in 25.5% (12 patients) and more than 50% in 53.2% (25 patients) and was also negative in 21.3% (10 patients). In terms of margin, lymph node, lower segment and parameter involvement, 44 patients (93.6%), 40 patients (85.11%), 43 patients (91.5%) and 46 patients (97.9%) were negative, respectively. Pathology risk of patients was also assessed and the results showed that this risk was high in 8 patients, moderate in 20 patients and low in 18 patients.\u003c/p\u003e \u003cp\u003eFollow-up of patients showed that only 18 patients (33.3%) did not require another treatment modality after chemotherapy and radical hysterectomy, while 66.7% (36 cases) of patients needed chemoradiotherapy after neoadjuvant chemotherapy and radical hysterectomy. Patients were also evaluated for recurrence, of which 88.4% had no recurrence, while recurrence was observed in 11.6% (5 cases) of patients.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFrequency distribution of demographic and clinical variables in patients diagnosed with stage IB-IIB cervical cancer treated with NACT and radical hysterectomy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean (S.D.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45.22 (9.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGravidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean (S.D.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.11 (2.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eStage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1B2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27 (44.26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1A2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (4.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1B3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (6.56)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (13.11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (21.31)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2A2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (6.56)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2A1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNACT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT\u0026thinsp;+\u0026thinsp;cis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e59 (93.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT\u0026thinsp;+\u0026thinsp;cis\u0026thinsp;+\u0026thinsp;rad\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (6.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eNACT courses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e59 (95.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePrimary pathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdenocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (10.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSCC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45 (90.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLVSI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25 (53.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22 (46.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eDepth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (25.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25 (53.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (21.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMarg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e44 (93.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (6.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40 (85.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (14.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLower Seg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43 (92.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (8.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e46 (97.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePathology risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (17.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20 (43.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18 (39.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eChemo-radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36 (66.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRecurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38 (88.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (11.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the results of the Progression-Free Survival (PFS) analysis. According to this Figure, the PFS rate after one year was 97.6% (95% CI: 84.2\u0026ndash;99.6), two-year PFS was 89.5% (95% CI: 74.4\u0026ndash;95.9), 5-year PFS was 89.5% (95% CI: 74.4\u0026ndash;95.9) and 10-year PFS were 89.5% (95% CI: 74.4\u0026ndash;95.9).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOf 48 patients who underwent NACT and radical hysterectomy, 29 (60.4% of patients) required chemoradiotherapy and 19 (39.6% of patients) did not require further treatment. The need for chemoradiotherapy in stage IIA, IB, and IIB were 33.3%, 66.67%, and 75%, respectively (p\u0026thinsp;=\u0026thinsp;0.28). Although the differences observed in the study population were not statistically significant, this difference could be clinically significant and may indicate a possible association between the disease stage and the need for chemoradiotherapy, which should be investigated in larger studies. The mean overall survival (OS) and progression-free survival (PFS) in the studied patients were 52.8 months (40.9\u0026ndash;64.7, CI:95%) and 51.1 months (39.3\u0026ndash;62.9, CI:95%), respectively.\u003c/p\u003e \u003cp\u003eThe recurrence rate in the study population was 10.5% (5 patients). The postoperative pathology demonstrated that 4 of them were in the high-risk group and underwent chemoradiotherapy, and the remaining patient was in the intermediate-risk group. After surgery, she applied for radiotherapy, but only received external radiotherapy and did not undergo brachytherapy, which highlights the importance of brachytherapy in preventing recurrence of cervical cancer.\u003c/p\u003e \u003cp\u003eOf the cases studied, 3 died (6.2%), all of which occurred in the recurrence group. 24 months after chemoradiotherapy, recurrence with bone metastasis was observed in one patient who was referred for chemotherapy and died 24 months after recurrence (OS\u0026thinsp;=\u0026thinsp;48 months); The second patient, considering the pathology after surgery, was a candidate for chemoradiotherapy who refused to receive treatment, and after 9 months, metastasis to the bladder was observed and the patients died after 2 months (OS\u0026thinsp;=\u0026thinsp;11 months); The third patient underwent chemoradiotherapy after surgery but did not receive brachytherapy and died 8 months after completing radiotherapy with bone metastasis. The mean PFS of patients with recurrence was 17.5 months (95% CI, 7\u0026ndash;28 months) and their OS was 25.6 months (95% CI, 3.8\u0026ndash;46.8 months).\u003c/p\u003e \u003cp\u003eNama et al. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] conducted a non-randomized study in 2018 to evaluate the increase in morbidity due to surgery with NACT compared to primary chemoradiotherapy in patients with IB2 stage cervical cancer, and compared the results of surgery and chemoradiotherapy; they found that the data were similar for patients with stage IB2 and IIA, therefore, they concluded that to date there is no conclusive evidence for a preferred treatment option for stage IB2 cervical cancer.\u003c/p\u003e \u003cp\u003eThe findings of the present study showed that both treatment failure and recurrence occurred in the first two years after treatment and after two years, the PFS rate remained 89.5% until the end of the study (end of 10 years).\u003c/p\u003e \u003cp\u003eIn a meta-analysis study published by Ye et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] in 2020, it was concluded that the short-term therapeutic effects of both treatment options were similar in patients with IB2-IIB stages of cervical cancer but the long-term effects of NACT along with surgery on OS and DFS were better in comparison with radiotherapy alone or CCRT; However, the limitations of this meta-analysis included the relatively small number of articles reviewed (5 articles), reviewing only survival rates and complications, and not reviewing the quality of life.\u003c/p\u003e \u003cp\u003eA meta-analysis by Cheng et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] found that CCRT in patients with IB2 / IIA2 stage cervical cancer was probably the best way to improve clinical outcomes, and suggested that phase III randomized trials be performed to assess this matter. Also, Lee et al. conducted a study [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and compared 85 patients with IB-IIB cervical cancer treated with NACT\u0026thinsp;+\u0026thinsp;S and 358 patients receiving CCRT; the authors concluded that in patients with IB-IIB cervical cancer, NACT treatment with surgery has no therapeutic advantage over CCRT.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAccording to the results of this study, it can be stated that a significant percentage of patients with stage IIA and IIB cervical cancer who are candidates for NACT followed by radical hysterectomy, would require another modality of treatment, which is chemoradiotherapy; therefore, it is recommended that by conducting prospective studies, in addition to investigating this issue, the choice of the first method of treatment of patients in these stages should be reconsidered so that the patient does not suffer from two treatments and related complications, and patients with these stages undergo chemoradiotherapy from the beginning. This theory requires a comparative study of overall survival, PFS, and quality of life after treatment between the patients receiving chemoradiotherapy and those receiving NACT and radical hysterectomy and subsequent chemoradiotherapy.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNACT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeoadjuvant chemotherapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCCRT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdjuvant concurrent Chemoradiation therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePFS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProgression-free survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eConfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate:\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Helsinki Declaration and was approved by the Tehran University of Medical Sciences ethics committee\u0026nbsp;(Code:\u0026nbsp;IR.TUMS.IKHC.REC.1399.382).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent for publication:\u003c/p\u003e\n\u003cp\u003eAll the patients signed the informed consent form.\u0026nbsp;A copy of the written consent is available for review by the Editor-in-Chief of this journal on request\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials:\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are\u0026nbsp;available for review by the Editor-in-Chief of this journal on request.\u003c/p\u003e\n\u003cp\u003eCompeting interests:\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interests.\u003c/p\u003e\n\u003cp\u003eFunding:\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003eConflicts of Interest:\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interests.\u003c/p\u003e\n\u003cp\u003eAuthors' contributions:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eS.N.\u0026nbsp;:\u0026nbsp;interpretation of data, writing and editing the article\u003c/li\u003e\n \u003cli\u003eAS.M.: Study conception and design\u003c/li\u003e\n \u003cli\u003eS.A.:\u0026nbsp;collecting data\u003c/li\u003e\n \u003cli\u003eSH.SH.:\u0026nbsp;collecting data\u003c/li\u003e\n \u003cli\u003eA.AH. :\u0026nbsp;data analysis\u003c/li\u003e\n \u003cli\u003eR.P. :\u0026nbsp;data analysis,\u0026nbsp;interpretation of data\u003c/li\u003e\n \u003cli\u003eN.Z.\u0026nbsp;:\u0026nbsp;Editing the final manuscript,\u0026nbsp;corresponding\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eAcknowledgements:\u003c/p\u003e\n\u003cp\u003eWe would like to thank the vice chancellor for the research of Tehran University of Medical Sciences and Imam Khomeini Hospital staffs for their supports. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors have read and approved the manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eFerlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359-86. doi: 10.1002/ijc.29210.\u003c/li\u003e\n \u003cli\u003eCatarino R, Petignat P, Dongui G, Vassilakos P. Cervical cancer screening in developing countries at a crossroad: Emerging technologies and policy choices. World J Clin Oncol. 2015;6:281-90. doi: 10.5306/wjco.v6.i6.281.\u003c/li\u003e\n \u003cli\u003eDjaladat H, Amini E, Xu W, Cai J, Daneshmand S, Lieskovsky G. Oncological Outcomes After Radical Prostatectomy for High-Risk Prostate Cancer Based on New Gleason Grouping System: A Validation Study From University of Southern California With 3,755 Cases. Prostate. 2017;77:743-8. doi: 10.1002/pros.23306.\u003c/li\u003e\n \u003cli\u003eYang Z, Chen D, Zhang J, Yao D, Gao K, Wang H, et al. The efficacy and safety of neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer: A randomized multicenter study. 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Neoadjuvant chemotherapy followed by radical surgery as an alternative treatment to concurrent chemoradiotherapy for young premenopausal patients with FIGO stage IIB squamous cervical carcinoma. Tumour Biol. 2015;36:4349-56. doi: 10.1007/s13277-015-3074-2.\u003c/li\u003e\n \u003cli\u003eGupta S, Maheshwari A, Parab P, Mahantshetty U, Hawaldar R, Sastri Chopra S, et al. Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial. J Clin Oncol. 2018;36:1548-55. doi: 10.1200/jco.2017.75.9985.\u003c/li\u003e\n \u003cli\u003eFrei E, 3rd. Clinical cancer research: an embattled species. Cancer. 1982;50:1979-92. doi: 10.1002/1097-0142(19821115)50:10\u0026lt;1979::aid-cncr2820501002\u0026gt;3.0.co;2-d.\u003c/li\u003e\n \u003cli\u003eRobova H, Rob L, Halaska MJ, Pluta M, Skapa P. Review of neoadjuvant chemotherapy and trachelectomy: which cervical cancer patients would be suitable for neoadjuvant chemotherapy followed by fertility-sparing surgery? Curr Oncol Rep. 2015;17:446. doi: 10.1007/s11912-015-0446-0.\u003c/li\u003e\n \u003cli\u003eAngioli R, Plotti F, Montera R, Aloisi A, Luvero D, Capriglione S, et al. Neoadjuvant chemotherapy plus radical surgery followed by chemotherapy in locally advanced cervical cancer. Gynecol Oncol. 2012;127:290-6. doi: 10.1016/j.ygyno.2012.07.104.\u003c/li\u003e\n \u003cli\u003ePeng YH, Wang XX, Zhu JS, Gao L. Neo-adjuvant chemotherapy plus surgery versus surgery alone for cervical cancer: Meta-analysis of randomized controlled trials. J Obstet Gynaecol Res. 2016;42:128-35. doi: 10.1111/jog.12896.\u003c/li\u003e\n \u003cli\u003eKim HS, Sardi JE, Katsumata N, Ryu HS, Nam JH, Chung HH, et al. Efficacy of neoadjuvant chemotherapy in patients with FIGO stage IB1 to IIA cervical cancer: an international collaborative meta-analysis. Eur J Surg Oncol. 2013;39:115-24. doi: 10.1016/j.ejso.2012.09.003.\u003c/li\u003e\n \u003cli\u003eIwata T, Miyauchi A, Suga Y, Nishio H, Nakamura M, Ohno A, et al. Neoadjuvant chemotherapy for locally advanced cervical cancer. Chin J Cancer Res. 2016;28:235-40. doi: 10.21147/j.issn.1000-9604.2016.02.13.\u003c/li\u003e\n \u003cli\u003eRamondetta L. What is the appropriate approach to treating women with incurable cervical cancer? J Natl Compr Canc Netw. 2013;11:348-55. doi: 10.6004/jnccn.2013.0044.\u003c/li\u003e\n \u003cli\u003eSh J, Molaeenezhad M. Textbook of sexual disorders. bijou and salemi publications. 2001;1540.\u003c/li\u003e\n \u003cli\u003eLe Borgne G, Mercier M, Woronoff AS, Guizard AV, Abeilard E, Caravati-Jouvenceaux A, et al. Quality of life in long-term cervical cancer survivors: a population-based study. Gynecol Oncol. 2013;129:222-8. doi: 10.1016/j.ygyno.2012.12.033.\u003c/li\u003e\n \u003cli\u003eNama V, Angelopoulos G, Twigg J, Murdoch JB, Bailey J, Lawrie TA. Type II or type III radical hysterectomy compared to chemoradiotherapy as a primary intervention for stage IB2 cervical cancer. Cochrane Database Syst Rev. 2018;10:Cd011478. doi: 10.1002/14651858.CD011478.pub2.\u003c/li\u003e\n \u003cli\u003eYe Q, Yang Y, Tang X, Li J, Li X, Zhang Y. Neoadjuvant Chemotherapy Followed by Radical Surgery versus Radiotherapy (with or without Chemotherapy) in Patients with Stage IB2, IIA, or IIB Cervical Cancer: A Systematic Review and Meta-Analysis. Dis Markers. 2020;2020:7415056. doi: 10.1155/2020/7415056.\u003c/li\u003e\n \u003cli\u003eCheng J, Liu B, Wang B, Long X, Li Z, Chen R, et al. Effectiveness comparisons of various therapies for FIGO stage IB2/IIA2 cervical cancer: a Bayesian network meta-analysis. BMC Cancer. 2021;21:1078. doi: 10.1186/s12885-021-08685-9.\u003c/li\u003e\n \u003cli\u003eLee J, Kim TH, Kim GE, Keum KC, Kim YB. Neoadjuvant chemotherapy followed by surgery has no therapeutic advantages over concurrent chemoradiotherapy in International Federation of Gynecology and Obstetrics stage IB-IIB cervical cancer. J Gynecol Oncol. 2016;27:e52. doi: 10.3802/jgo.2016.27.e52.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Chemo-Radiotherapy, Neoadjuvant Chemotherapy, Radical Hysterectomy, Cervical Cancer, Progression-Free Survival","lastPublishedDoi":"10.21203/rs.3.rs-4392903/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4392903/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChemo-radiotherapy is recommended as the standard treatment for advanced cervical cancer, and neoadjuvant chemotherapy (NACT) can be beneficial for patients on long radiotherapy waiting lists. In this study, we aimed to evaluate the need for chemo-radiotherapy after NACT and radical hysterectomy in women with stage IB-IIB cervical cancer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a retrospective cohort study. All patients of gynecologic oncology clinic of Imam Khomeini Hospital, Tehran, Iran who were diagnosed with stage IB-IIB cervical cancer and were treated with NACT and radical hysterectomy between 2010 and 2020, were included in this study. The records of all patients who met the inclusion criteria were evaluated during the study period. The interested outcomes and progression-free survival (PFS) were assessed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, clinical files of 613 patients with cervical cancer were studied and among them, 63 patients (10.2% of patients) underwent NACT. Eighteen patients (33.3%) did not require another treatment modality after chemotherapy and radical hysterectomy, while 66.7% (36 cases) of patients needed chemo-radiotherapy after NACT and radical hysterectomy, and recurrence was observed in 11.6% (5 cases) of patients. The 1-, 5- and 10-year PFS rate was 97.6% (95% CI: 84.2-99.6), 89.5% (95% CI: 74.4-95.9) and 89.5% (95% CI: 74.4-95.9), respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIt can be concluded that a significant percentage of patients who are candidates for NACT followed by radical hysterectomy, would require another modality of treatment, which is chemo-radiotherapy; therefore, it is recommended that by conducting prospective studies, in addition to investigating this issue, the choice of the first method of patients treatment in these stages should be reconsidered so that the patient does not suffer from two treatments and related complications, and patients undergo chemo-radiotherapy from the beginning.\u003c/p\u003e","manuscriptTitle":"Chemo-radiotherapy after neoadjuvant chemotherapy and radical hysterectomy in women with stage IB-IIB cervical cancer: Do we need to change the therapeutic approach? a cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-28 17:56:59","doi":"10.21203/rs.3.rs-4392903/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6f4bbe8a-5a6e-4f13-a8fb-696b379f1141","owner":[],"postedDate":"May 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-23T07:00:24+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-28 17:56:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4392903","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4392903","identity":"rs-4392903","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}