Stage-dependent differences of long-term outcomes between chemoradiotherapy and surgery for squamous cell carcinoma of the anal canal: A multicenter retrospective cohort study​

Stage-dependent differences of long-term outcomes between chemoradiotherapy and surgery for squamous cell carcinoma of the anal canal: A multicenter retrospective 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 Stage-dependent differences of long-term outcomes between chemoradiotherapy and surgery for squamous cell carcinoma of the anal canal: A multicenter retrospective cohort study​ Norihiro Shimoike, Koya Hida, Takashi Sakamoto, Kazutaka Obama, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9309874/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 5 You are reading this latest preprint version Abstract Objectives: Efficacy comparisons between surgery and chemoradiotherapy (CRT) in the treatment of squamous cell carcinoma (SCC) of the anal canal have not been performed enough. Herein, we aim to reveal the long-term outcomes of CRT and surgery for SCC of the anal canal and to assess the optimal clinical stage-dependent treatment strategy. Methods: We retrospectively assessed patients with SCC who were treated via CRT or surgery between 1991 and 2015 at 47 medical institutions in Japan. The associations of the treatment strategy with the overall survival (OS) and the cumulative incidence of the first recurrence categorized as local failure, inguinal lymph node metastasis, or distant recurrence were examined. Results: The OS following CRT and surgery for clinical stages ≤ II were similar (adjusted hazard ratio [aHR] 0.89, 95% confidence intervals [CI] 0.48–1.63); however, surgery was associated with lower OS for clinical stage III (aHR 1.82, 95% CI 1.06–3.11). Local failure was more likely to occur after CRT, and inguinal node metastasis occurred more frequently after surgery. Conclusions: The optimal treatment may differ according to the clinical stage. For patients with clinical stage I or II, surgical resection including local excision could be a treatment of choice. Squamous cell carcinoma of the anal canal Chemoradiotherapy Surgery Long-term outcomes Stage-dependent treatment Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction The current standard treatment for squamous cell carcinoma (SCC) of the anal canal is chemoradiotherapy (CRT), regardless of the cancer stage[ 1 , 2 ]. Since Nigro et al. reported complete tumor regression after CRT for anal canal cancer[ 3 ], CRT has overtaken surgical resection to achieve cure with preserved quality of life (QOL). Currently, surgery is regarded as a salvage treatment for residual or recurrent tumors. Salvage surgery following CRT is associated with severe wound-related complications, and 25%–30% of patients who received CRT experienced local recurrence or residual tumors for which salvage surgery is the only curative treatment option[ 4 – 8 ]. Among those who underwent salvage abdominoperineal resection (APR), 20%–70% had wound-related complications such as perineal wound breakdown and wound infection[ 9 – 12 ], which required a long healing period of > 3 months[ 11 , 12 ]. A high rate of local failure and potentially consequent long-lasting morbidity causes impaired QOL. Although primary surgical resection for SCC of the anal canal is considered to result in an inferior 5-year survival, to the best of our knowledge, there is no comparative study between CRT and primary surgery for SCC of the anal canal[ 1 , 2 ]. Moreover, the oncological outcome was based on surgery performed > 4 decades ago[ 13 ]. However, recent improvements in surgical techniques based on technological development and an understanding of precise anatomy might achieve a better prognosis. Therefore it is meaningful to compare oncological outcomes between CRT and primary surgery. It is also not unnatural to suppose appropriate treatment can differ depending on the tumor stage as with SCC of the esophagus[ 14 , 15 ]. This study aims to reveal the long-term outcomes of CRT and surgery for SCC of the anal canal and assess the optimal treatment strategy depending on the clinical stage. Methods Study design and population This is a secondary analysis of a multicenter retrospective cohort study[ 16 ] in which 47 medical institutions participated as a project of the Japanese Society for Cancer of the Colon and Rectum (JSCCR). In the original study, we reviewed the records of patients with anal canal cancer who were treated between 1991 and 2015 at the 47 aforementioned institutions. The present study assessed the patients with SCC who were treated using either CRT or surgery. Patients who received only radiotherapy or chemotherapy and those with stage IV cancer were excluded from the present study. This study was approved by the ethical committee of JSCCR and was conducted following the principles of the Declaration of Helsinki. Cancer staging The definition of the anal canal (the conventional anal canal and the perianal skin within 5cm from the anal verge) and tumor staging were assessed according to the TNM classification (8th edition)[ 17 ]. Tumors whose sizes were not measured were classified as TxN0 when there was no invasion to the nearby organ and no evidence of distant or lymph node metastasis, which were handled as stage ≤ II. Tumors with lymph node metastasis and without distant metastasis were classified as stage III regardless of the T factor. Treatment The initial treatment for SCC of the anal canal was categorized as either CRT or surgery. Planned surgery following neoadjuvant treatment (radiotherapy and/or chemotherapy) was still categorized as surgery. Outcomes of interest and statistical analyses Characteristics of patients, tumors, and treatments were summarized using appropriate descriptive statistics. The primary outcome of interest was the overall survival (OS), which was defined as the time-lapse from the start of treatment to all-cause death. Patients who were alive at the last follow-up appointment were right-censored. OS was estimated using the Kaplan–Meier method and compared using the log-rank test. Cox proportional hazard models were then constructed to assess the impact of initial treatment on survival after adjusting for potential confounders; sex (female or male), age (≤ 70 or > 70 years), and clinical stage of the tumor (stages I, IIa, IIb, IIIa, IIIb, IIIc, TxN0, and TxN1). The proportional hazard assumption was checked graphically and statistically using Schoenfeld residuals, and no apparent violations were detected. The secondary outcome of interest was the first recurrence after the initial treatment. The first recurrent site was categorized as local failure, inguinal lymph node metastasis, or distant recurrence. Local failure included residual cancer after the initial treatment. The cumulative incidence of the first recurrence at each site was calculated and compared using Gray’s method, with death and recurrence at other sites being considered competing risk events[ 18 , 19 ]. We compared outcomes between CRT and surgery within each cancer stage. We also compared outcomes between APR and local excision in the subcohort of patients who underwent surgery for stage ≤ II cancer to assess the impact of the surgical procedure on survival. We performed two series of sensitivity analyses. One excluded patients who received neoadjuvant treatment because of the possible prognostic impact of neoadjuvant treatment. In the other sensitivity analysis, we performed the same analysis excluding perianal cancer. All statistical analyses were performed using R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria). Given the exploratory nature of the present study, we reported the point and interval estimates of the statistics and refrained from the binary use of P values according to the current recommendation on statistics[ 20 ]. Results Patient characteristics A total of 391 patients were treated for SCC of the anal canal via CRT or surgery during the study period (Fig. 1 ). Nineteen of these patients were excluded because they had stage IV cancer. CRT and surgery were performed for 37 and 16 patients with stage I cancer, 53 and 31 with stage II cancer, 42 and 22 with TxN0 cancer, and 111 and 60 with stage III cancer, respectively. The background and treatment characteristics at each stage are summarized in Tables 1 and 2 . Among patients who underwent surgery, 12.9% of those with stage II, 36.4% of those with TxN0, and 25.0% of those with stage III received neoadjuvant treatment. Local excision was performed for 62.5% of those with stage I, 41.9% of those with stage II, 68.2% of those with TxN0, and 6.7% of those with stage III. CRTs were performed more recently, whereas surgeries were performed constantly throughout the study period (Supplementary Fig. 1). Table 1 Background characteristics of the patients Stage I Stage II TxN0 Stage III CRT Surgery CRT Surgery CRT Surgery CRT Surgery n = 37 n = 16 n = 53 n = 31 n = 42 n = 22 n = 111 n = 60 Sex, n (%) Male 9 (24.3) 8 (50.0) 12 (22.6) 10 (32.3) 14 (33.3) 5 (22.7) 30 (27.0) 13 (21.7) Female 28 (75.7) 8 (50.0) 41 (77.4) 21 (67.7) 28 (66.7) 17 (77.3) 81 (73.0) 47 (78.3) Age, median (IQR) 64 (53–70) 66 (56–77.3) 65 (56–64) 68 (60–78) 67 (59–73) 65 (60–71) 74 (57–72) 70 (59–77) Location, n (%) Perianal skin 1 (2.7) 2 (12.5) 2 (3.8) 4 (12.9) 2 (4.8) 1 (4.5) 8 (7.2) 3 (5.0) Surgical anal canal 36 (97.3) 14 (87.5) 51 (96.2) 27 (87.1) 40 (95.2) 21 (95.5) 103 (92.8) 57 (95.0) Histology, n (%) Well differentiated 7 (18.9) 1 (6.3) 5 (9.4) 6 (19.4) 9 (21.4) 4 (18.2) 12 (10.8) 12 (20.0) Moderately differentiated 7 (18.9) 5 (31.3) 10 (18.9) 11 (35.5) 10 (23.8) 1 (4.5) 25 (22.5) 17 (28.3) Poorly differentiated 7 (18.9) 2 (12.5) 7 (13.2) 3 (9.7) 0 (0.0) 2 (9.1) 15 (13.5) 5 (8.3) Differentiation unknown 15 (40.5) 4 (25.0) 29 (54.7) 7 (22.6) 23 (54.8) 11 (50.0) 59 (53.2) 23 (38.3) Basaloid cell carcinoma 1 (2.7) 2 (12.5) 1 (1.9) 4 (12.9) 0 (0.0) 4 (18.2) 0 (0.0) 1 (1.7) Adenosquamous cell carcinoma 0 (0.0) 2 (12.5) 1 (1.9) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (3.3) HPV, n (%) Positive 0 (0.0) 0 (0.0) 1 (1.9) 0 (0.0) 1 (2.4) 0 (0.0) 0 (0.0) 0 (0.0) Negative 6 (16.2) 2 (12.5) 6 (11.3) 1 (3.2) 1 (2.4) 0 (0.0) 8 (7.2) 5 (8.3) Unknown 31 (83.8) 14 (87.5) 46 (86.8) 30 (96.8) 40 (95.2) 22 (100) 103 (92.8) 55 (91.7) HIV, n (%) Positive 1 (2.7) 1 (6.3) 1 (1.9) 1 (3.2) 0 (0.0) 0 (0.0) 4 (3.6) 0 (0.0) Negative 22 (59.5) 8 (50.0) 31 (58.5) 15 (48.4) 28 (66.7) 15 (68.2) 63 (56.8) 31 (51.7) Unknown 14 (37.8) 7 (43.8) 21 (39.6) 15 (48.4) 14 (33.3) 7 (31.8) 44 (39.6) 29 (48.3) Abbreviations: IQR, interquartile range; HPV, human papillomavirus; HIV, human immunodeficiency virus. Table 2 Treatment characteristics of the patients Stage I Stage II TxN0 Stage III CRT Surgery CRT Surgery CRT Surgery CRT Surgery n = 37 n = 16 n = 53 n = 31 n = 42 n = 22 n = 111 n = 60 Range of RT, n (%) Localized on tumor 1 (2.7) 4 (7.5) 0 (0.0) 4 (3.6) Pelvis 14 (37.8) 7 (13.2) 3 (7.1) 16 (14.4) Pelvis and groin 19 (51.4) 37 (69.8) 31 (73.8) 83 (74.8) Unknown 3 (8.1) 5 (9.4) 8 (19.0) 8 (7.2) Does of RT, median (IQR) 59 (54–59.2) 59 (54–59.4) 59 (54–60) 59 (59–59.4) Neoadjuvant, n (%) RT 0 (0.0) 0 (0.0) 6 (27.3) 5 (8.3) Chemotherapy 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) CRT 0 (0.0) 4 (12.9) 2 (9.1) 10 (16.7) Not performed 16 (100.0) 27 (87.1) 14 (63.6) 45 (75.0) Agent of chemotherapy Doublet 34 (91.9) 47 (88.7) 36 (85.7) 102 (91.9) Single agent 3 (8.1) 5 (9.4) 6 (14.3) 8 (7.2) Unknown 0 1 (1.9) 0 1 (0.9) Surgical procedure, n (%) Local excision 10 (62.5) 13 (41.9) 15 (68.2) 4 (6.7) APR 5 (31.3) 15 (48.4) 5 (22.7) 51 (85.0) Others 1 (6.3) 3 (9.7) 2 (9.1) 5 (8.3) LPND, n (%) Hemilateral 1 (6.3) 3 (9.7) 0 (0.0) 10 (16.7) Bylateral 0 (0.0) 4 (12.9) 0 (0.0) 22 (36.7) Not performed 14 (87.5) 24 (77.4) 15 (68.2) 26 (43.3) Unknown 1 (6.3) 0 (0.0) 7 (31.8) 2 (3.3) Abbreviations: RT, radiotherapy; IQR, interquartile range; CRT, chemoradiotherapy; APR, abdonimoperineal resection; LPND, lateral pelvic lymph node dissection. Overall survival As the survival data of one patient with stage II cancer was missing, complete case analyses excluding the patient were conducted. 5-year OS following CRT and surgery were 93.5% (95% CI: 85.2%–100%) and 92.9% (95% CI: 80.3%–100%) for stage I, 72.9% (95% CI: 60.7%–87.6%) and 84.1% (95% CI: 70.4%–100%) for stage II, 78.8% (95% CI: 66.7%–93.2%) and 73.2% (95% CI: 55.4%–96.8%) for TxN0, and 73.9% (95% CI: 65.7%–83.2%) and 59.9% (95% CI: 48.1%–74.5%) for stage III, respectively (Fig. 2 ). Cox regression analyses showed the impact of surgery on patients’ survival compared to that of CRT; adjusted hazard ratio [aHR]: 0.89 (95% CI 0.48–1.63) in the stage ≤ II subcohort, and aHR: 1.82 (95% CI 1.06–3.11) in the stage III subcohort (Table 3 ). Table 3 Multivariable analyses to assess the impact of treatment strategy on the overall survival Stage ≤ II Stage III HR (95% CI) P value HR (95% CI) P value Treatment CRT Reference Reference Surgery 0.89 (0.48–1.63) 0.70 1.82 (1.06–3.11) 0.03 Sex Female Reference Reference Male 1.76 (0.97–3.20) 0.06 2.03 (1.15–3.61) 0.02 Age ≤ 70 Reference Reference > 70 2.28 (1.27–4.08) 0.01 1.83 (1.08–3.11) 0.02 cStage I Reference NA IIA 2.89 (1.05–7.92) 0.04 NA IIB 3.94 (1.03–15.0) 0.04 NA TxN0 3.30 (1.24–8.78) 0.02 NA IIIA NA Reference IIIB NA 1.22 (0.54–2.77) 0.64 IIIC NA 1.25 (0.69–2.27) 0.47 TxN1 NA 1.71 (0.67–4.36) 0.26 Abbreviations: CRT, chemoradiotherapy; HR, hazard ratio. First recurrence The cumulative incidences of local failure as the first recurrence at 5 years following CRT and surgery were 21.6% (95% CI: 8.4%–34.9%) and 7.1% (95% CI: 0%–20.6%) for stage I, 27.5% (95% CI: 15.2%–39.8%) and 6.9% (95% CI: 0%–16.1%) for stage II, 11.9% (95% CI: 2.1%–21.7%) and 9.6% (95% CI: 0%–22.1%) for TxN0, and 38.0% (95% CI: 29.0%–47.1%) and 6.7% (95% CI: 0.4%–13.1%) for stage III, respectively (Fig. 3 ). The cumulative incidences of inguinal lymph node recurrence as the first recurrence at 5 years following CRT and surgery were 0% (95% CI: 0%–0%) and 7.1% (95% CI: 0%–20.6%) for stage I, 2.2% (95% CI: 0%–6.5%) and 17.5% (95% CI: 3.5%–31.6%) for stage II, 0% (95% CI: 0%–0%) and 0% (95% CI: 0%–0%) for TxN0, and 0.9% (95% CI: 0%–2.7%) and 17.5% (95% CI: 7.6%–27.3%) for stage III, respectively (Fig. 4 ). The cumulative incidences of distant recurrence as the first recurrence at 5 years following CRT and surgery were 0% (95% CI: 0%–0%) and 7.1% (95% CI: 0%–20.6%) for stage I, 4.0% (95% CI: 0%–9.5%) and 3.2% (95% CI: 0%–9.5%) for stage II, 7.1% (95% CI: 0%–14.9%) and 15.4% (95% CI: 8.2%–31.5%) for TxN0, and 8.3% (95% CI: 3.1%–13.4%) and 12.3% (95% CI: 3.8%–20.8%) for stage III, respectively (Supplementary Fig. 2). APR vs. local excision The 5-year OS was 81.6% (95% CI: 67.9%–98.0%) among patients who received APR and 82.7% (95% CI: 69.8%–98.0%) among patients who underwent local excision (Supplementary Fig. 3). The cumulative incidences of first recurrence at 5 years following APR and local excision were 3.3% (95% CI: 0%–9.8%) and 11.6% (95% CI: 0.9%–22.2%) for local failure, 10.0% (95% CI: 0%–20.8%) and 8.9% (95% CI: 0%–18.5%) for inguinal node recurrence, and 10.1% (95% CI: 0%–20.9%) and 6.7% (95% CI: 0%–15.8%) for distant recurrence, respectively. Sensitivity analyses The results of the two series of sensitivity analyses did not differ significantly from the results of the main analysis. (Supplementary figures. 4–11, Supplementary tables 1,2). Discussion This multicenter retrospective cohort study suggested that the impact of the treatment strategy on patients’ survival differed according to the clinical stage of SCC of the anal canal. The OS following CRT and surgery were similar when the clinical stage was ≤ II, whereas surgery was associated with lower OS in the stage III cohort. These tendencies were confirmed after adjusting for potential confounders via multivariable analyses. Per our findings, CRT was performed for more recent cases. Although such an imbalance in the treatment period may cause a bias, the bias should be in favor of CRT group. Therefore, our results were conservative for the surgery group. Our results in the stage ≤ II subcohort were in line with those of previous studies that reported similar OS in patients with T1N0 SCC of the anal canal who were treated via either CRT or surgical excision[ 21 , 22 ]. Additionally, the present study revealed differences in the recurrent pattern between patients who received CRT and those who underwent surgery. Local failure was more likely to occur after CRT, and inguinal lymph node metastasis occurred more frequently after surgery. The local failure rate of 11.9%–38.0% following CRT in our cohort was compatible with the findings of previous studies[ 4 – 8 ]. It is assumed that the CRT group had good OS in spite of the high local failure rate thanks to salvage therapy after local failure, but there are no data on post-failure therapy, which is a limitation. The lower frequency of inguinal node recurrence following CRT might be due to irradiation to the groin[ 23 ]. As the inguinal node metastasis was reported to be a risk factor for poor survival[ 24 , 25 ], the high incidence of inguinal lymph node metastasis could be associated with a poor prognosis following surgery in the stage III subcohort. Since we only had data on the site of the first recurrence, potential differences in the secondary recurrent pattern including distant recurrence may also affect the prognosis. However, to the best of our knowledge, this is the first report that describes the recurrence pattern in the two treatment strategies of CRT and surgery. Regarding the surgical procedure, no apparent differences in OS were detected between APR and local excision in the present study. However, local failure seemed to occur more frequently in the local excision group. The discrepancy in the similar OS and the high incidence of local failure could be explained by the availability of CRT or salvage APR following local failure. Although we have to consider the indication bias, local excision could be enough if complete tumor resection is possible. The local excision can contribute to improved QOL without stoma nor sequelae following RT such as digestive and skin toxicities[ 26 , 27 ]. When SCC of the anal canal is treated by surgical resection, irradiation to the groin should be considered to prevent inguinal node recurrence. Our study has several limitations to be considered. First, residual confounders may have skewed the results. Our data did not include patients’ comorbidities, which could have affected both the treatment selection and patients’ survival. Second, information about the treatment following recurrence was unavailable. Salvage treatment has an important role to play in determining patients’ survival. Third, our data did not include information about patients’ QOL following each treatment strategy. The posttreatment QOL is also an important factor to consider when choosing a treatment strategy, as well as survival outcomes. In conclusion, the present study described the long-term outcomes of CRT and surgery for SCC of the anal canal. Our findings suggested that the optimal treatment differed depending on the clinical stage. For patients with clinical stage I or II SCC of the anal canal, surgical resection including local excision could be a treatment of choice. More rigorous comparative studies are needed to further investigate our findings. Declarations Authors’ contributions N Shimoike: conceptualization, interpreting the results, writing original draft. K Hida: conceptualization, interpreting the results, reviewing and editing the manuscript. T Sakamoto: conceptualization, reviewing and editing the manuscript. K Obama: conceptualization, reviewing and editing the manuscript. K Yamada: conceptualization, reviewing and editing the manuscript. K Sugihara: conceptualization, reviewing and editing the manuscript. All authors approved the final manuscript. Ethics approval and consent to participate This study was approved by the ethical committee of Japanese Society for Cancer of the Colon and Rectum and was conducted following the principles of the Declaration of Helsinki. The requirement for written informed consent was waived because of the retrospective nature of the study. Acknowledgements This study was conducted as a part of the project of the Research for Characteristics and Staging of Anal Canal Cancer from the Japanese Society for Cancer of the Colon and Rectum. The authors would like to express their deepest gratitude to Professor Ajioka, who provided invaluable guidance and support throughout this study. Disclosure KH received lecture fee from Johnson and Johnson, Intuitive Surgical, Terumo Corporation, Olympus Corporation, and Medtronic. 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Dis Colon Rectum 56(10):1125–1133 Devisetty K, Mell LK, Salama JK et al (2009) A multi-institutional acute gastrointestinal toxicity analysis of anal cancer patients treated with concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy. Radiother Oncol 93(2):298–301 Supplementary Files Supplementarytablesandfigures.docx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Major revisions 27 Apr, 2026 Reviewers agreed at journal 17 Apr, 2026 Reviewers invited by journal 16 Apr, 2026 Editor assigned by journal 14 Apr, 2026 First submitted to journal 13 Apr, 2026 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. 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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-9309874","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":624592223,"identity":"0aa4ed33-97e1-498f-beb2-eef6b1e2b79a","order_by":0,"name":"Norihiro Shimoike","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-4547-2293","institution":"Japan Red Cross Osaka Hospital","correspondingAuthor":true,"prefix":"","firstName":"Norihiro","middleName":"","lastName":"Shimoike","suffix":""},{"id":624592224,"identity":"f11aa2f5-b066-4671-8445-35b560ab54ec","order_by":1,"name":"Koya Hida","email":"","orcid":"https://orcid.org/0000-0001-7210-7075","institution":"Kyoto University Hospital: Kyoto Daigaku Igakubu Fuzoku Byoin","correspondingAuthor":false,"prefix":"","firstName":"Koya","middleName":"","lastName":"Hida","suffix":""},{"id":624592225,"identity":"c728d771-ad5e-4cbd-9d07-e31fe4dec2a9","order_by":2,"name":"Takashi Sakamoto","email":"","orcid":"","institution":"Kyoto University Hospital: Kyoto Daigaku Igakubu Fuzoku Byoin","correspondingAuthor":false,"prefix":"","firstName":"Takashi","middleName":"","lastName":"Sakamoto","suffix":""},{"id":624592226,"identity":"7f0e6d2f-74bd-4aa2-b53e-ea4d8244dbd6","order_by":3,"name":"Kazutaka Obama","email":"","orcid":"","institution":"Kyoto University Hospital: Kyoto Daigaku Igakubu Fuzoku Byoin","correspondingAuthor":false,"prefix":"","firstName":"Kazutaka","middleName":"","lastName":"Obama","suffix":""},{"id":624592227,"identity":"6b40e787-59ac-482f-9c37-f23411798250","order_by":4,"name":"Kazutaka Yamada","email":"","orcid":"","institution":"Takano Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kazutaka","middleName":"","lastName":"Yamada","suffix":""},{"id":624592228,"identity":"c36bae51-c4a4-4d4d-8028-15b8c6c6a7b4","order_by":5,"name":"Kenichi Sugihara","email":"","orcid":"","institution":"Tokyo Medical and Dental University: Tokyo Ika Shika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Kenichi","middleName":"","lastName":"Sugihara","suffix":""}],"badges":[],"createdAt":"2026-04-03 07:12:55","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9309874/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9309874/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107834619,"identity":"3a95e15b-6d50-43ba-89f1-670ca3a3b52d","added_by":"auto","created_at":"2026-04-26 15:46:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":416004,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the participant selection procedure\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9309874/v1/92a513d15cc638a234bc84ca.png"},{"id":107869966,"identity":"d7b4aa3f-046e-4800-bc34-914ed4340fc8","added_by":"auto","created_at":"2026-04-27 07:38:33","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":840857,"visible":true,"origin":"","legend":"\u003cp\u003eComparisons of overall survival between chemoradiotherapy and surgery for (a) stage I, (b) stage II, (c) TxN0 and (d) stage III. P values were obtained from log-rank test. OS, overall survival; CRT, chemoradiotherapy.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-9309874/v1/0a0011d98068a973a833d69c.png"},{"id":107869372,"identity":"1f912ffc-c686-4973-baf0-8067492aa3fc","added_by":"auto","created_at":"2026-04-27 07:36:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":903284,"visible":true,"origin":"","legend":"\u003cp\u003eComparisons of the cumulative incidence of local failure between chemoradiotherapy and surgery for (a) stage I, (b) stage II, (c) TxN0 and (d) stage III. P values were obtained from Gray’s test. CRT, chemoradiotherapy.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-9309874/v1/a564c4894d62aaa774942c25.png"},{"id":107870007,"identity":"bd62bbdf-6b5e-4e52-bce0-2f45ee36cebf","added_by":"auto","created_at":"2026-04-27 07:38:37","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":870512,"visible":true,"origin":"","legend":"\u003cp\u003eComparisons of the cumulative incidence of inguinal node metastasis between chemoradiotherapy and surgery for (a) stage I, (b) stage II, (c) TxN0 and (d) stage III. P values were obtained from Gray’s test. CRT, chemoradiotherapy.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-9309874/v1/7d508a8b6ee39b86faed15fb.png"},{"id":108491067,"identity":"79f475d4-baae-4825-b589-943b217324b2","added_by":"auto","created_at":"2026-05-05 09:51:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3392042,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9309874/v1/1f30e32a-2f80-448d-8528-d1b591d3d657.pdf"},{"id":107834622,"identity":"ebcdca4f-0526-489a-a1a1-05762586b5ac","added_by":"auto","created_at":"2026-04-26 15:46:22","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":1604648,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytablesandfigures.docx","url":"https://assets-eu.researchsquare.com/files/rs-9309874/v1/9a48a267c50bc865c96cece1.docx"}],"financialInterests":"","formattedTitle":"Stage-dependent differences of long-term outcomes between chemoradiotherapy and surgery for squamous cell carcinoma of the anal canal: A multicenter retrospective cohort study​","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe current standard treatment for squamous cell carcinoma (SCC) of the anal canal is chemoradiotherapy (CRT), regardless of the cancer stage[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]. Since Nigro et al. reported complete tumor regression after CRT for anal canal cancer[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e], CRT has overtaken surgical resection to achieve cure with preserved quality of life (QOL). Currently, surgery is regarded as a salvage treatment for residual or recurrent tumors.\u003c/p\u003e \u003cp\u003eSalvage surgery following CRT is associated with severe wound-related complications, and 25%–30% of patients who received CRT experienced local recurrence or residual tumors for which salvage surgery is the only curative treatment option[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e–\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. Among those who underwent salvage abdominoperineal resection (APR), 20%–70% had wound-related complications such as perineal wound breakdown and wound infection[\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e–\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e], which required a long healing period of \u0026gt; 3 months[\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]. A high rate of local failure and potentially consequent long-lasting morbidity causes impaired QOL.\u003c/p\u003e \u003cp\u003eAlthough primary surgical resection for SCC of the anal canal is considered to result in an inferior 5-year survival, to the best of our knowledge, there is no comparative study between CRT and primary surgery for SCC of the anal canal[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]. Moreover, the oncological outcome was based on surgery performed \u0026gt; 4 decades ago[\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, recent improvements in surgical techniques based on technological development and an understanding of precise anatomy might achieve a better prognosis. Therefore it is meaningful to compare oncological outcomes between CRT and primary surgery. It is also not unnatural to suppose appropriate treatment can differ depending on the tumor stage as with SCC of the esophagus[\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aims to reveal the long-term outcomes of CRT and surgery for SCC of the anal canal and assess the optimal treatment strategy depending on the clinical stage.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch3\u003eStudy design and population\u003c/h3\u003e\u003cp\u003eThis is a secondary analysis of a multicenter retrospective cohort study[\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e] in which 47 medical institutions participated as a project of the Japanese Society for Cancer of the Colon and Rectum (JSCCR). In the original study, we reviewed the records of patients with anal canal cancer who were treated between 1991 and 2015 at the 47 aforementioned institutions. The present study assessed the patients with SCC who were treated using either CRT or surgery. Patients who received only radiotherapy or chemotherapy and those with stage IV cancer were excluded from the present study. This study was approved by the ethical committee of JSCCR and was conducted following the principles of the Declaration of Helsinki.\u003c/p\u003e\u003ch2\u003eCancer staging\u003c/h2\u003e\u003cp\u003eThe definition of the anal canal (the conventional anal canal and the perianal skin within 5cm from the anal verge) and tumor staging were assessed according to the TNM classification (8th edition)[\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]. Tumors whose sizes were not measured were classified as TxN0 when there was no invasion to the nearby organ and no evidence of distant or lymph node metastasis, which were handled as stage ≤ II. Tumors with lymph node metastasis and without distant metastasis were classified as stage III regardless of the T factor.\u003c/p\u003e\u003ch3\u003eTreatment\u003c/h3\u003e\u003cp\u003eThe initial treatment for SCC of the anal canal was categorized as either CRT or surgery. Planned surgery following neoadjuvant treatment (radiotherapy and/or chemotherapy) was still categorized as surgery.\u003c/p\u003e\u003ch3\u003eOutcomes of interest and statistical analyses\u003c/h3\u003e\u003cp\u003eCharacteristics of patients, tumors, and treatments were summarized using appropriate descriptive statistics. The primary outcome of interest was the overall survival (OS), which was defined as the time-lapse from the start of treatment to all-cause death. Patients who were alive at the last follow-up appointment were right-censored. OS was estimated using the Kaplan–Meier method and compared using the log-rank test. Cox proportional hazard models were then constructed to assess the impact of initial treatment on survival after adjusting for potential confounders; sex (female or male), age (≤ 70 or \u0026gt; 70 years), and clinical stage of the tumor (stages I, IIa, IIb, IIIa, IIIb, IIIc, TxN0, and TxN1). The proportional hazard assumption was checked graphically and statistically using Schoenfeld residuals, and no apparent violations were detected.\u003c/p\u003e\u003cp\u003eThe secondary outcome of interest was the first recurrence after the initial treatment. The first recurrent site was categorized as local failure, inguinal lymph node metastasis, or distant recurrence. Local failure included residual cancer after the initial treatment. The cumulative incidence of the first recurrence at each site was calculated and compared using Gray’s method, with death and recurrence at other sites being considered competing risk events[\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWe compared outcomes between CRT and surgery within each cancer stage. We also compared outcomes between APR and local excision in the subcohort of patients who underwent surgery for stage ≤ II cancer to assess the impact of the surgical procedure on survival. We performed two series of sensitivity analyses. One excluded patients who received neoadjuvant treatment because of the possible prognostic impact of neoadjuvant treatment. In the other sensitivity analysis, we performed the same analysis excluding perianal cancer.\u003c/p\u003e\u003cp\u003eAll statistical analyses were performed using R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria). Given the exploratory nature of the present study, we reported the point and interval estimates of the statistics and refrained from the binary use of P values according to the current recommendation on statistics[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eA total of 391 patients were treated for SCC of the anal canal via CRT or surgery during the study period (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Nineteen of these patients were excluded because they had stage IV cancer. CRT and surgery were performed for 37 and 16 patients with stage I cancer, 53 and 31 with stage II cancer, 42 and 22 with TxN0 cancer, and 111 and 60 with stage III cancer, respectively. The background and treatment characteristics at each stage are summarized in Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Among patients who underwent surgery, 12.9% of those with stage II, 36.4% of those with TxN0, and 25.0% of those with stage III received neoadjuvant treatment. Local excision was performed for 62.5% of those with stage I, 41.9% of those with stage II, 68.2% of those with TxN0, and 6.7% of those with stage III. CRTs were performed more recently, whereas surgeries were performed constantly throughout the study period (Supplementary Fig.\u0026nbsp;1).\u003c/p\u003e \u003cp\u003e \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\u003eBackground characteristics of the patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eStage I\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eStage II\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eTxN0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eStage III\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (24.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5 (22.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30 (27.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e13 (21.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (75.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (77.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21 (67.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17 (77.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e81 (73.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e47 (78.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (53\u0026ndash;70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (56\u0026ndash;77.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65 (56\u0026ndash;64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68 (60\u0026ndash;78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e67 (59\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e65 (60\u0026ndash;71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e74 (57\u0026ndash;72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e70 (59\u0026ndash;77)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerianal skin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3 (5.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical anal canal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (97.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (87.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51 (96.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27 (87.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e40 (95.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e21 (95.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e103 (92.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e57 (95.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistology, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWell differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (18.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (9.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (19.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12 (10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e12 (20.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerately differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (18.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (31.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (18.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11 (35.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25 (22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e17 (28.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoorly differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (18.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e15 (13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDifferentiation unknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (40.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (54.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23 (54.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e59 (53.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e23 (38.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasaloid cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (1.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenosquamous cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHPV, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (16.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (83.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (87.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 (86.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30 (96.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e40 (95.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e22 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e103 (92.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e55 (91.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHIV, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (59.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (58.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (48.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15 (68.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e63 (56.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e31 (51.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (37.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (39.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (48.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7 (31.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e44 (39.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e29 (48.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eAbbreviations: IQR, interquartile range; HPV, human papillomavirus; HIV, human immunodeficiency virus.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTreatment characteristics of the patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eStage I\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eStage II\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eTxN0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eStage III\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange of RT, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocalized on tumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePelvis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (37.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16 (14.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePelvis and groin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (51.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (69.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31 (73.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e83 (74.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (9.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8 (19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDoes of RT, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (54\u0026ndash;59.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59 (54\u0026ndash;59.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e59 (54\u0026ndash;60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e59 (59\u0026ndash;59.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e10 (16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27 (87.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e14 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e45 (75.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAgent of chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDoublet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (91.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (88.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e36 (85.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e102 (91.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingle agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (9.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical procedure, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocal excision\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (41.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15 (68.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4 (6.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (31.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (48.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5 (22.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e51 (85.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLPND, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemilateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e10 (16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBylateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e22 (36.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (87.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24 (77.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15 (68.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e26 (43.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7 (31.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2 (3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eAbbreviations: RT, radiotherapy; IQR, interquartile range; CRT, chemoradiotherapy; APR, abdonimoperineal resection; LPND, lateral pelvic lymph node dissection.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOverall survival\u003c/h2\u003e \u003cp\u003eAs the survival data of one patient with stage II cancer was missing, complete case analyses excluding the patient were conducted. 5-year OS following CRT and surgery were 93.5% (95% CI: 85.2%\u0026ndash;100%) and 92.9% (95% CI: 80.3%\u0026ndash;100%) for stage I, 72.9% (95% CI: 60.7%\u0026ndash;87.6%) and 84.1% (95% CI: 70.4%\u0026ndash;100%) for stage II, 78.8% (95% CI: 66.7%\u0026ndash;93.2%) and 73.2% (95% CI: 55.4%\u0026ndash;96.8%) for TxN0, and 73.9% (95% CI: 65.7%\u0026ndash;83.2%) and 59.9% (95% CI: 48.1%\u0026ndash;74.5%) for stage III, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Cox regression analyses showed the impact of surgery on patients\u0026rsquo; survival compared to that of CRT; adjusted hazard ratio [aHR]: 0.89 (95% CI 0.48\u0026ndash;1.63) in the stage\u0026thinsp;\u0026le;\u0026thinsp;II subcohort, and aHR: 1.82 (95% CI 1.06\u0026ndash;3.11) in the stage III subcohort (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariable analyses to assess the impact of treatment strategy on the overall survival\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStage\u0026thinsp;\u0026le;\u0026thinsp;II\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eStage III\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.89 (0.48\u0026ndash;1.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.82 (1.06\u0026ndash;3.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.76 (0.97\u0026ndash;3.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.03 (1.15\u0026ndash;3.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le; 70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt; 70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.28 (1.27\u0026ndash;4.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.83 (1.08\u0026ndash;3.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecStage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.89 (1.05\u0026ndash;7.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.94 (1.03\u0026ndash;15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTxN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.30 (1.24\u0026ndash;8.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIIB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.22 (0.54\u0026ndash;2.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIIIC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.25 (0.69\u0026ndash;2.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTxN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.71 (0.67\u0026ndash;4.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: CRT, chemoradiotherapy; HR, hazard ratio.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eFirst recurrence\u003c/h3\u003e\n\u003cp\u003eThe cumulative incidences of local failure as the first recurrence at 5 years following CRT and surgery were 21.6% (95% CI: 8.4%\u0026ndash;34.9%) and 7.1% (95% CI: 0%\u0026ndash;20.6%) for stage I, 27.5% (95% CI: 15.2%\u0026ndash;39.8%) and 6.9% (95% CI: 0%\u0026ndash;16.1%) for stage II, 11.9% (95% CI: 2.1%\u0026ndash;21.7%) and 9.6% (95% CI: 0%\u0026ndash;22.1%) for TxN0, and 38.0% (95% CI: 29.0%\u0026ndash;47.1%) and 6.7% (95% CI: 0.4%\u0026ndash;13.1%) for stage III, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The cumulative incidences of inguinal lymph node recurrence as the first recurrence at 5 years following CRT and surgery were 0% (95% CI: 0%\u0026ndash;0%) and 7.1% (95% CI: 0%\u0026ndash;20.6%) for stage I, 2.2% (95% CI: 0%\u0026ndash;6.5%) and 17.5% (95% CI: 3.5%\u0026ndash;31.6%) for stage II, 0% (95% CI: 0%\u0026ndash;0%) and 0% (95% CI: 0%\u0026ndash;0%) for TxN0, and 0.9% (95% CI: 0%\u0026ndash;2.7%) and 17.5% (95% CI: 7.6%\u0026ndash;27.3%) for stage III, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The cumulative incidences of distant recurrence as the first recurrence at 5 years following CRT and surgery were 0% (95% CI: 0%\u0026ndash;0%) and 7.1% (95% CI: 0%\u0026ndash;20.6%) for stage I, 4.0% (95% CI: 0%\u0026ndash;9.5%) and 3.2% (95% CI: 0%\u0026ndash;9.5%) for stage II, 7.1% (95% CI: 0%\u0026ndash;14.9%) and 15.4% (95% CI: 8.2%\u0026ndash;31.5%) for TxN0, and 8.3% (95% CI: 3.1%\u0026ndash;13.4%) and 12.3% (95% CI: 3.8%\u0026ndash;20.8%) for stage III, respectively (Supplementary Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eAPR vs. local excision\u003c/h3\u003e\n\u003cp\u003eThe 5-year OS was 81.6% (95% CI: 67.9%\u0026ndash;98.0%) among patients who received APR and 82.7% (95% CI: 69.8%\u0026ndash;98.0%) among patients who underwent local excision (Supplementary Fig.\u0026nbsp;3). The cumulative incidences of first recurrence at 5 years following APR and local excision were 3.3% (95% CI: 0%\u0026ndash;9.8%) and 11.6% (95% CI: 0.9%\u0026ndash;22.2%) for local failure, 10.0% (95% CI: 0%\u0026ndash;20.8%) and 8.9% (95% CI: 0%\u0026ndash;18.5%) for inguinal node recurrence, and 10.1% (95% CI: 0%\u0026ndash;20.9%) and 6.7% (95% CI: 0%\u0026ndash;15.8%) for distant recurrence, respectively.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity analyses\u003c/h2\u003e \u003cp\u003eThe results of the two series of sensitivity analyses did not differ significantly from the results of the main analysis. (Supplementary figures. 4\u0026ndash;11, Supplementary tables 1,2).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis multicenter retrospective cohort study suggested that the impact of the treatment strategy on patients\u0026rsquo; survival differed according to the clinical stage of SCC of the anal canal. The OS following CRT and surgery were similar when the clinical stage was \u0026le;\u0026thinsp;II, whereas surgery was associated with lower OS in the stage III cohort. These tendencies were confirmed after adjusting for potential confounders via multivariable analyses. Per our findings, CRT was performed for more recent cases. Although such an imbalance in the treatment period may cause a bias, the bias should be in favor of CRT group. Therefore, our results were conservative for the surgery group. Our results in the stage\u0026thinsp;\u0026le;\u0026thinsp;II subcohort were in line with those of previous studies that reported similar OS in patients with T1N0 SCC of the anal canal who were treated via either CRT or surgical excision[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdditionally, the present study revealed differences in the recurrent pattern between patients who received CRT and those who underwent surgery. Local failure was more likely to occur after CRT, and inguinal lymph node metastasis occurred more frequently after surgery. The local failure rate of 11.9%\u0026ndash;38.0% following CRT in our cohort was compatible with the findings of previous studies[\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It is assumed that the CRT group had good OS in spite of the high local failure rate thanks to salvage therapy after local failure, but there are no data on post-failure therapy, which is a limitation. The lower frequency of inguinal node recurrence following CRT might be due to irradiation to the groin[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. As the inguinal node metastasis was reported to be a risk factor for poor survival[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], the high incidence of inguinal lymph node metastasis could be associated with a poor prognosis following surgery in the stage III subcohort. Since we only had data on the site of the first recurrence, potential differences in the secondary recurrent pattern including distant recurrence may also affect the prognosis. However, to the best of our knowledge, this is the first report that describes the recurrence pattern in the two treatment strategies of CRT and surgery.\u003c/p\u003e \u003cp\u003eRegarding the surgical procedure, no apparent differences in OS were detected between APR and local excision in the present study. However, local failure seemed to occur more frequently in the local excision group. The discrepancy in the similar OS and the high incidence of local failure could be explained by the availability of CRT or salvage APR following local failure. Although we have to consider the indication bias, local excision could be enough if complete tumor resection is possible. The local excision can contribute to improved QOL without stoma nor sequelae following RT such as digestive and skin toxicities[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. When SCC of the anal canal is treated by surgical resection, irradiation to the groin should be considered to prevent inguinal node recurrence.\u003c/p\u003e \u003cp\u003eOur study has several limitations to be considered. First, residual confounders may have skewed the results. Our data did not include patients\u0026rsquo; comorbidities, which could have affected both the treatment selection and patients\u0026rsquo; survival. Second, information about the treatment following recurrence was unavailable. Salvage treatment has an important role to play in determining patients\u0026rsquo; survival. Third, our data did not include information about patients\u0026rsquo; QOL following each treatment strategy. The posttreatment QOL is also an important factor to consider when choosing a treatment strategy, as well as survival outcomes.\u003c/p\u003e \u003cp\u003eIn conclusion, the present study described the long-term outcomes of CRT and surgery for SCC of the anal canal. Our findings suggested that the optimal treatment differed depending on the clinical stage. For patients with clinical stage I or II SCC of the anal canal, surgical resection including local excision could be a treatment of choice. More rigorous comparative studies are needed to further investigate our findings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAuthors’ contributions\u003c/p\u003e\n\u003cp\u003eN Shimoike: conceptualization, interpreting the results, writing original draft. K Hida: conceptualization, interpreting the results, reviewing and editing the manuscript. T Sakamoto: conceptualization, reviewing and editing the manuscript. K Obama: conceptualization, reviewing and editing the manuscript. K Yamada: conceptualization, reviewing and editing the manuscript. K Sugihara: conceptualization, reviewing and editing the manuscript.\u003c/p\u003e\n\u003cp\u003eAll authors approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis study was approved by the ethical committee of Japanese Society for Cancer of the Colon and Rectum and was conducted following the principles of the Declaration of Helsinki. The requirement for written informed consent was waived because of the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eThis study was conducted as a part of the project of the Research for Characteristics and Staging of Anal Canal Cancer from the Japanese Society for Cancer of the Colon and Rectum. The authors would like to express their deepest gratitude to Professor Ajioka, who provided invaluable guidance and support throughout this study.\u003c/p\u003e\n\u003cp\u003eDisclosure\u003c/p\u003e\n\u003cp\u003eKH received lecture fee from Johnson and Johnson, Intuitive Surgical, Terumo Corporation, Olympus Corporation, and Medtronic.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eSupported by HEALTH SCIENCE CENTER, GENERAL FOUNDATION\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBenson AB, Venook AP, Al-Hawary MM et al (2018) Anal Carcinoma, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 16(7):852\u0026ndash;871\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRao S, Guren MG, Khan K et al (2021) Anal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNigro ND, Vaitkevicius VK, Considine B (1974) Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum 17(3):354\u0026ndash;356\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeiffert D, Tournier-Rangeard L, G\u0026eacute;rard JP et al (2012) Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 trial. J Clin Oncol 30(16):1941\u0026ndash;1948\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEpidermoid anal cancer (1996) : results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet 348(9034):1049\u0026ndash;1054\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAjani JA, Winter KA, Gunderson LL et al (2008) Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA 299(16):1914\u0026ndash;1921\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBartelink H, Roelofsen F, Eschwege F et al (1997) Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 15(5):2040\u0026ndash;2049\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNorthover J, Glynne-Jones R, Sebag-Montefiore D et al (2010) Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer 102(7):1123\u0026ndash;1128\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhouti L, Houvenaeghel G, Moutardier V et al (2005) Salvage abdominoperineal resection after failure of conservative treatment in anal epidermoid cancer. Dis Colon Rectum 48(1):16\u0026ndash;22\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchiller DE, Cummings BJ, Rai S et al (2007) Outcomes of salvage surgery for squamous cell carcinoma of the anal canal. Ann Surg Oncol 14(10):2780\u0026ndash;2789\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNilsson PJ, Svensson C, Goldman S et al (2002) Salvage abdominoperineal resection in anal epidermoid cancer. Br J Surg 89(11):1425\u0026ndash;1429\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMariani P, Ghanneme A, De la Rochefordi\u0026egrave;re A et al (2008) Abdominoperineal resection for anal cancer. Dis Colon Rectum 51(10):1495\u0026ndash;1501\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRyan DP, Compton CC, Mayer RJ (2000) Carcinoma of the anal canal. N Engl J Med 342(11):792\u0026ndash;800\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAjani JA, D'Amico TA, Bentrem DJ et al (2019) Esophageal and Esophagogastric Junction Cancers, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 17(7):855\u0026ndash;883\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLordick F, Mariette C, Haustermans K et al (2016) Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 27(suppl 5):v50\u0026ndash;v7\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamada K, Saiki Y, Komori K et al (2022) Characteristics of anal canal cancer in Japan. Cancer Med 11(14):2735\u0026ndash;2743\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrierley JD, Gospodarowicz MK, Wittekind C (2017) TNM classification of malignant tumours. Wiley, Eighth Edition\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGray RJ (1988) A Class of K-Sample Tests for Comparing the Cumulative Incidence of a Competing Risk. Annals Stat 16(3):1141\u0026ndash;1154\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDignam JJ, Kocherginsky MN (2008) Choice and interpretation of statistical tests used when competing risks are present. J Clin Oncol 26(24):4027\u0026ndash;4034\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWasserstein RL, Schirm AL, Lazar NA (2019) Moving to a World Beyond p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Am Stat 73(sup1):1\u0026ndash;19\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChai CY, Tran Cao HS, Awad S et al (2018) Management of Stage I Squamous Cell Carcinoma of the Anal Canal. JAMA Surg 153(3):209\u0026ndash;215\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKole AJ, Stahl JM, Park HS et al (2017) Predictors of Nonadherence to NCCN Guideline Recommendations for the Management of Stage I Anal Canal Cancer. J Natl Compr Canc Netw 15(3):355\u0026ndash;362\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrtholan C, Resbeut M, Hannoun-Levi JM et al (2012) Anal canal cancer: management of inguinal nodes and benefit of prophylactic inguinal irradiation (CORS-03 Study). Int J Radiat Oncol Biol Phys 82(5):1988\u0026ndash;1995\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShepherd NA, Scholefield JH, Love SB et al (1990) Prognostic factors in anal squamous carcinoma: a multivariate analysis of clinical, pathological and flow cytometric parameters in 235 cases. Histopathology 16(6):545\u0026ndash;555\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin ACH, Hakim A, Kellish AS et al (2020) Inguinal Lymph Node Dissection Does Not Improve Overall Survival in Anal Cancer Nodal Disease. J Surg Res 255:13\u0026ndash;22\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDoyen J, Benezery K, Follana P et al (2013) Predictive factors for early and late local toxicities in anal cancer treated by radiotherapy in combination with or without chemotherapy. Dis Colon Rectum 56(10):1125\u0026ndash;1133\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDevisetty K, Mell LK, Salama JK et al (2009) A multi-institutional acute gastrointestinal toxicity analysis of anal cancer patients treated with concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy. Radiother Oncol 93(2):298\u0026ndash;301\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Squamous cell carcinoma of the anal canal, Chemoradiotherapy, Surgery, Long-term outcomes, Stage-dependent treatment","lastPublishedDoi":"10.21203/rs.3.rs-9309874/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9309874/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjectives: Efficacy comparisons between surgery and chemoradiotherapy (CRT) in the treatment of squamous cell carcinoma (SCC) of the anal canal have not been performed enough. Herein, we aim to reveal the long-term outcomes of CRT and surgery for SCC of the anal canal and to assess the optimal clinical stage-dependent treatment strategy.\u003c/p\u003e\n\u003cp\u003eMethods: We retrospectively assessed patients with SCC who were treated via CRT or surgery between 1991 and 2015 at 47 medical institutions in Japan. The associations of the treatment strategy with the overall survival (OS) and the cumulative incidence of the first recurrence categorized as local failure, inguinal lymph node metastasis, or distant recurrence were examined.\u003c/p\u003e\n\u003cp\u003eResults: The OS following CRT and surgery for clinical stages ≤ II were similar (adjusted hazard ratio [aHR] 0.89, 95% confidence intervals [CI] 0.48–1.63); however, surgery was associated with lower OS for clinical stage III (aHR 1.82, 95% CI 1.06–3.11). Local failure was more likely to occur after CRT, and inguinal node metastasis occurred more frequently after surgery.\u003c/p\u003e\n\u003cp\u003eConclusions: The optimal treatment may differ according to the clinical stage. For patients with clinical stage I or II, surgical resection including local excision could be a treatment of choice.\u003c/p\u003e","manuscriptTitle":"Stage-dependent differences of long-term outcomes between chemoradiotherapy and surgery for squamous cell carcinoma of the anal canal: A multicenter retrospective cohort study​","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-26 15:46:17","doi":"10.21203/rs.3.rs-9309874/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revisions","date":"2026-04-28T01:50:20+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2026-04-17T09:46:10+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-17T00:37:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-15T03:46:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Clinical Oncology","date":"2026-04-13T09:24:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"78c90d34-47cb-4e02-b9f7-c7eb8a826fb5","owner":[],"postedDate":"April 26th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-28T05:51:53+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-26 15:46:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9309874","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9309874","identity":"rs-9309874","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}