Lower inguinal lymph node metastases in anal cancer: prevalence, predictors, and exact locations

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Nilsson, Jonas Scherman This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8598273/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 17 You are reading this latest preprint version Abstract Background In anal caner, the lower inguinal subregion is the most common site of regional lymph node metastases (LNM) occurring outside the borders of the major contouring guidelines. With the aim of informing future contouring guidelines, the present study investigated the exact locations and predictors of lower inguinal LNM. Methods Baseline FDG-PET-CTs from a consecutive population-based series of anal cancer patients ( n = 190) were used to identify LNM in the lower inguinal subregion, defined as ≥ 10 mm below the saphenofemoral junction (SFJ). Lymph nodes with an FDG uptake above the mediastinal blood pool were considered metastatic irrespective of size. The distances from the center of each LNM to the SFJ, the great saphenous vein (GSV), and the femoral vessels were measured. The characteristics of patients with lower inguinal LNM were compared with other patients using non-parametric tests. Results Lower inguinal LNM were identified in 8.4% of the patients. For every lower inguinal LNM the distance was shorter to the GSV vein (median 7 mm; range 4–19) compared to the femoral vessels (median 21 mm; range 9–37). Only one lower inguinal LNM was located more than 10 mm medial to the GSV. A distal margin of 2.5 cm from the SFJ covered all lower inguinal LNM in 97 of 103 (95%) inguinal regions with LNM and in 375 of 380 (98.7%) inguinal regions in all patients. Patients with lower inguinal LNM had larger tumors and more often stage T4, which might open for an individualization of the inferior border of the elective clinical target volume (eCTV). Conclusions In the lower inguinal subregion LNM follow the GSV rather than the femoral vessels. To capture the different anatomical compartments of the inguinal region future contouring guidelines should present separate recommendations for different inguinal subregions. In addition, they should be aiming at providing individual risk-adapted recommendations rather than a ‘one size fits all’. Anal cancer anal carcinoma inguinal lymph node metastasis contouring elective clinical target volume Figures Figure 1 Figure 2 Figure 3 Background Metastatic cells can spread from primary tumors in the lower pelvis to the inguinal region through lymph vessels collectively referred to as the superficial inguinal pathway or the ano-inguinal lymphatic drainage (AILD) [ 1 , 2 ]. The most common inguinal sentinel node is the saphenofemoral node, located close to the saphenofemoral junction (SFJ), where the great saphenous vein (GSV) traverses the cribriform fascia, passes through the fossa ovalis, and enters the femoral vein [ 3 ]. However, lymph node metastasis (LNM) can occur also in other parts of the inguinal region [ 4 – 7 ]. In many studies undertaken by surgeons the inguinal region has been meticulously subdivided into different parts, mainly been based on the level of the SFJ, the femoral vessels, and the deep fascia [ 3 , 4 , 8 – 10 ]. In contrast, articles written by radiation oncologist have generally been less detailed, which might have contributed to the lack of consensus in the radiation oncology community regarding the optimal borders of the elective clinical target volume (eCTV) [ 11 – 15 ]. Dapper et al analyzed the pattern of LNM in squamous cell carcinoma of the anus (anal cancer) and compared it with the major international contouring guidelines. All locoregional LNM located outside the eCTV were found in the inguinal region, most commonly in the lower part of it [ 16 ]. Motivated by this and with the aim of informing future contouring guidelines, we decided to undertake an analysis of lower inguinal LNM in anal cancer, defined as ≥ 10 mm below the SFJ. As part of a previous study, we mapped LNM in anal cancer patients [ 5 ]. In the present study, we reanalyzed the study population specifically focusing on lower inguinal LNM. Predictors of metastatic spread to the lower inguinal region, as well as the exact location of lower inguinal LNM, were investigated. Methods All patients with anal cancer treated with radiotherapy at Skåne University Hospital during the years 2009 through 2017 were selected from an institutional database ( n = 203). Since Skåne University Hospital is the only hospital in the region treating anal cancer the cohort represents a consecutive population-based series. Most ( n = 190) had undergone baseline staging with [18F]-fluorodeoxyglucose positron emission tomography with computed tomography (PET-CT). The PET-CTs were done in the supine position with a slice thickness of 2.5-3 mm, either frog-legged or with a standard knee cushion. As part of a previous publication, these PET-CTs were retrospectively evaluated with the aim of assessing lymph nodes in a structured way [ 5 ]. Lymph nodes with an uptake above the mediastinal blood pool were considered PET-positive irrespective of size. In the following, PET-positive lymph nodes are denoted LNM. Each LNM was allocated to a nodal region and a nodal subregion. Specifically, the inguinal region was further subdivided into three subregions: the saphenofemoral subregion (within 10 mm above and below the SFJ, which was defined as the first CT-slice with visible fat separating the GSV and the femoral vein), the upper inguinal subregion (≥ 10 mm above the SFJ), and the lower inguinal subregion (≥ 10 mm below the SFJ) [ 5 ]. The aim of the present study was to further analyze LNM in the lower inguinal subregion. To that end, the distance from the center of the most caudally located lower inguinal LNM to the SFJ was measured. Furthermore, the distance from the center of each lower inguinal LNM to the closest border of the GSV and the femoral vessels (vein or artery, whichever was closest), respectively, was measured in the axial plane. In case of branching of the great GSV, only the medial branch was considered. The clock face direction of each lower inguinal LNM in relation to vessels in the right groin (left medial converted to right medial) was also noted. In-transit metastases along the AILD in the labia major/scrotum and the subcutaneous tissue of the medial thigh were not counted as inguinal LNM but were reported. Descriptive statistics were used to summarize the characteristics of the study population. Continuous variables were reported with means or medians and value ranges. The Mann-Whitney U test was used to compare continous variables. Categorical variables were compared using crosstabs and statistical significance was assessed with the chi-squared test or Fisher’s exact test, as appropriate. Statistical analyses were conducted using SPSS version 30.0. All significance tests were 2-sided, and P values < 0.05 were considered statistically significant. Figure 1 was based on screenshots of diagnostic images and edited using Inkscape version 1.3.2. Figure 2 was done in RStudio version 2025.09.2. Results Patient and tumor characteristics are presented in Table 1 . The mean age was 65.1 years and 79.5% were female. Distant metastasis at diagnosis was seen in 7.9%. As previously reported, LNM were identified in 54.2% ( n = 103), and inguinal LNM in 39.5% ( n = 75) of the patients. Inguinal LNM were unilateral in 47 patients and bilateral in 28 patients, corresponding to 103 inguinal regions with a total of 182 pathologic lymph nodes; 119 located in the saphenofemoral subregion, 41 in the upper inguinal subregion, and 22 in the lower inguinal subregion. Table 1 Patient and tumor characteristics All patients with PET-CT, n = 190 (%) Patients with lymph node metastasis on PET-CT, n = 103 (%) Age at diagnosis, mean (years) 65.1 64.7 Female 151 (79.5) 81 (78.6) Tumor size, median (mm; range) 45 (4-150) 55 (4-150) Perianal extention a 99 (52.1) 61 (59.2) T stage b 1. 18 (9.5) 3 (2.9) 2. 86 (45.3) 37 (35.9) 3. 43 (22.6) 31 (30.1) 4. 43 (22.6) 32 (31.1) Regional or CI/PA lymph node metastasis c 103 (54.2) 103 (100) Inguinal lymph node metastasis c 75 (39.5) 75 (72.8) Distant metastasis a,d 15 (7.9) 14 (13.6) Abbreviations: CI/PA, common iliac or para-aortic; PET-CT, [18F]-fluorodeoxyglucose positron emission tomography with computed tomography with computed tomography a Extension of the primary tumor outside the anal verge b TNM8 c Deauville score 3–5 d Includes common iliac and para-aortic lymph node metastasis Prevalence of lower inguinal LNM Out of 190 patients, 16 (8.4%) had lower inguinal LNM, of whom 2 bilateral, corresponding to 18 lower inguinal subregions with a total of 22 pathologic lymph nodes. Thus, 18 of 103 (17.5%) inguinal regions with LNM harbored LNM in the lower inguinal subregion. Axial PET-CT images of the center of the most caudally located lower inguinal LNM in each individual patient are presented in Fig. 1 . In addition to LNM in the lower inguinal subregion, 5 also harbored LNM in the upper inguinal subregion and 16 in the saphenofemoral subregion. Accordingly, only 2 inguinal regions had lower inguinal LNM without the synchronous occurrence of saphenofemoral LNM. Exact location of lower inguinal LNM The exact location of each lower inguinal LNM in relation to the GSV and the femoral vessels is presented in Fig. 2 . A clock face of the right groin shows that 59% were medial (1:00–4:00) and 36% were lateral (7:00–11:00) to the GSV. In contrast, no LNM were located lateral or posterior to the femoral vessels. For every lower inguinal LNM the distance was shorter to the GSV vein (median 7 mm; range 4–19) than to the femoral vessels (median 21 mm; range 9–37) (Fig. 2 , Supplementary Table S1 ). Only one LNM was located more than 10 mm medial to the GSV. Distance from the saphenofemoral junction The center of the most caudally located lower inguinal LNM in each inguinal region was located 10–43 mm below the SFJ (median 18 mm; Supplementary Table S1 ). One patient in this cohort had in-transit metastases in the AILD, not counted as lower inguinal LNM. The center of the most caudal AILD metastasis, located in labia major, was 60 mm below the SFJ (Fig. 3 ). Lower inguinal LNM were not more caudal in men (median 15 mm below the SFJ; range 10–25) than in women (median 20 mm below the SFJ; range 10–43) ( P = 0.11). Table 2 shows what proportion of lower inguinal LNM that are covered by a distal margin of 2, 3 and 4 cm from the SFJ, respectively. A distal margin of 2.5 cm from the SFJ covered all lower inguinal LNM in 97 of 103 (95%) inguinal regions with LNM and in 375 of 380 (98.7%) inguinal regions in all patients. Table 2 Proportion of inguinal regions with all lower inguinal LNM covered across different subgroups of patients, using different distal margins Distal margin Inguinal regions in all patients Inguinal regions with LNM Inguinal regions with lower inguinal LNM 2 cm distal to the SFJ 372 of 380 (97.9%) 95 of 103 (92.2%) 10 of 18 (55.6%) 3 cm distal to the SFJ 377 of 380 (99.2%) 100 of 103 (97.1%) 15 of 18 (83.3%) 4 cm distal to the SFJ 378 of 380 (99.5%) 101 of 103 (98.1%) 16 of 18 (88.9%) Abbreviations: LNM, lymph node metastasis; SFJ, saphenofemoral junction Predictors of lower inguinal LNM Compared to all other patients with LNM (Table 3a), as well as compared to patients with LNM in the saphenofemoral or upper inguinal subregions (Table 3b), patients with lower inguinal LNM had larger tumors and more often stage T4 ( P < 0.05). Perianal tumor extension was non-significantly more common among patients with lower inguinal LNM compared to all other patients with LNM ( P = 0.06) but not compared to patients with LNM in the saphenofemoral or upper inguinal subregions ( P = 1.00). Table 3a . Lower inguinal LNM among all patients with LNM Lower inguinal LNM No, n = 87 (%) Yes, n = 16 (%) P Primary tumor size, median (mm; range) 50 (4-150) 70 (52-100) 0.002 T stage 0.02 T1-3 64 (90%) 7 (10%) T4 23 (72%) 9 (28%) Perianal extension of the primary tumor 0.06 No 39 (93%) 3 (7%) Yes 48 (79%) 13 (21%) Gender 0.74 Female 69 (85%) 12 (15%) Male 18 (82%) 4 (18%) Abbreviations: LNM, lymph node metastasis Table 3b . Lower inguinal LNM among patients with inguinal LNM Lower inguinal LNM No, n = 59 (%) Yes, n = 16 (%) P Primary tumor size, median (mm; range) 60 (4-150) 70 (52-100) 0.02 T stage 0.02 T1-3 44 (86%) 7 (14%) T4 15 (63%) 9 (37%) Perianal extension of the primary tumor 1.00 No 14 (82%) 3 (18%) Yes 45 (78%) 13 (22%) Gender 1.00 Female 44 (79%) 12 (21%) Male 15 (79%) 4 (21%) Abbreviations: LNM, lymph node metastasis Discussion In this cohort of unselected anal cancer patients the prevalence of lower inguinal LNM was 8.4%. In 16 of 18 groins with lower inguinal LNM the saphenofemoral node was also metastatic, but two patients had lower inguinal LNM without a saphenofemoral LNM, indicating that in rare cases there can be a direct spread of tumor cells to lower inguinal lymph nodes. Leijte et al found no lower inguinal sentinel lymph nodes in anal cancer [ 3 ], but larger studies in penile cancer and vulvar cancer have reported that lower inguinal sentinel nodes and isolated metastases do occur in a minority of the patients [ 4 , 9 , 10 ]. The results of our study clearly showed that lower inguinal LNM follow the GSV rather than the femoral vessels. In fact, not a single lower inguinal LNM was close to the femoral vessels, suggesting that LNM in anal cancer are rare, or even absent, posterior to the deep fascia at ≥ 10 mm below the SFJ. This is supported by Lengele et al who summarized the anatomical literature and concluded that the lowest deep inguinal node, if present, is situated against the femoral vein just below the SFJ [ 17 ]. Consequently, instructions for the contouring of the lower inguinal subregion should be based on other anatomical landmarks than the femoral vessels. Out of the 22 lower inguinal LNM in our study, only one was located more than 10 mm medial to the GSV. In that patient, multiple in-transit metastases in the AILD were also present (Fig. 3 ). It is possible that the LNM classified as ‘lower inguinal’ was in fact also an in-transit AILD metastasis, rather than a true LNM. Anyway, a medial margin of 7–8 mm from the border of the GSV seems sufficient to cover most lower inguinal LNM in anal cancer, which is in line with the recommendation of 10 mm medial to the center of the GSV proposed by Chang et al in a recent and informative study of inguinal LNM in 181 patients with various pelvic malignancies (34 anal cancer cases) [ 18 ]. The inferior border of the eCTV varies between different contemporary inguinal contouring guidelines for anal cancer. Most of them use bony landmarks, such as the lower edge of the lesser trochanter [ 11 , 12 , 15 ] or the ischial tuberosity [ 14 ]. Although more research is needed to define the optimal landmark, we believe that the most appropriate inferior border of the eCTV is defined by a caudal margin from the SFJ, which is also recommended by the RTOG [ 13 ]. The saphenofemoral node, located close to the SFJ, is a central component of the superficial inguinal pathway and the SFJ should therefore be more representative of lymph node topographic anatomy than any bony landmark. One limitation when comparing the results of different studies based on cross sectional imaging is that most authors have not stated a clear definition of the SFJ. We defined the SFJ as the first axial CT-slice with visible fat separating the GSV and the femoral vein. In our study, a caudal margin of 2.5 cm below the SFJ covered all lower inguinal LNM in 95% of the inguinal regions with LNM. An increased likelihood of lower inguinal LNM was seen in larger tumors and in T4 tumors, which might open for an individualization of the eCTV: for patients with T1-2 tumors a smaller margin below the SFJ might suffice, whereas for patients with advanced tumors invading the lower anal canal or perianal area and for patients with LNM in the saphenofemoral subregion a larger caudal margin could be more appropriate. Further research is needed and should be aiming at presenting data which can constitute a foundation for an individualization of the eCTV. There are limitations to our study. First, we measured the distance from the center of LNM to vessels, which is not perfect in case of displacement of the center caused by enlargement or anisotropic growth. For enlarged lymph nodes abutting vessels the methodology would likely overestimate rather than underestimate the distance between vessels and nonenlarged micrometastatic lymph nodes. Second, using PET-CT instead of pathological verification entails a risk of both false negative and false positive findings. Third, despite (to the best of our knowledge) being the largest anal cancer lymph node mapping study to date, the study cohort is still relatively small, and the results should be replicated by others before any firm conclusions can be drawn. To conclude, the results of our study indicate that lower inguinal LNM occur in 8.4% of unselected anal cancer patients, with higher frequencies in patients with stage T4 or large primary tumors. In the lower inguinal subregion LNM follow the GSV rather than the femoral vessels. To capture the different anatomical compartments of the groin future contouring guidelines should present separate recommendations for different inguinal subregions. Also, they should be aiming at providing individual risk-adapted recommendations rather than a ‘one size fits all’. Abbreviations AILD, ano-inguinal lymphatic drainage; eCTV, elective clinical target volume; GSV, great saphenous vein; LNM, lymph node metastasis; PET-CT, [18F]-fluorodeoxyglucose positron emission tomography with computed tomography; SFJ, saphenofemoral junction. Declarations Ethics approval and consent to participate The study was approved by the Regional Ethical Review Board in Lund (Dnr 2013/742) and by the Swedish Ethical Review Authority (Dnr 2019/02669). The need for informed consent was waived given the retrospective nature of the study. Consent for publication Not applicable. Supplementary Table S1 . Lower inguinal lymph node metastasis in relation to vessels. Funding The work was funded by The Swedish Cancer Society (Grant number 23-2639). Author Contribution MPN conceived of the study and collected the clinical data. MPN remeasured distances to anatomical landmarks (which had previously been done by radiologist Anna Frennered). MPN carried out the statistical analyses. MPN and JS analyzed and interpreted the results. MNL and JS drafted the manuscript and approved the final manuscript. Data Availability The present data is summarized in this paper. The complete dataset can be retrieved from the corresponding author on reasonable request. References Dapper H, Habl G, Hirche C, Münch S, Oechsner M, Mayinger M, Sauter C, Combs SE, Habermehl D. Dosimetric quantification of the incidental irradiation of the 'true' (deep) ano-inguinal lymphatic drainage of anal cancer patients not described in conventional contouring guidelines. Acta Oncol. 2018;57(6):825–30. Paño B, Sebastià C, Buñesch L, Mestres J, Salvador R, Macías NG, Nicolau C. Pathways of lymphatic spread in male urogenital pelvic malignancies. Radiographics. 2011;31(1):135–60. Leijte JA, Valdés Olmos RA, Nieweg OE, Horenblas S. Anatomical mapping of lymphatic drainage in penile carcinoma with SPECT-CT: implications for the extent of inguinal lymph node dissection. Eur Urol. 2008;54(4):885–90. 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Supplementary Files SupplementaryTableS1.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 03 Apr, 2026 Reviews received at journal 21 Mar, 2026 Reviews received at journal 10 Mar, 2026 Reviews received at journal 01 Mar, 2026 Reviews received at journal 27 Feb, 2026 Reviewers agreed at journal 20 Feb, 2026 Reviewers agreed at journal 19 Feb, 2026 Reviewers agreed at journal 19 Feb, 2026 Reviewers agreed at journal 19 Feb, 2026 Reviews received at journal 10 Feb, 2026 Reviewers agreed at journal 31 Jan, 2026 Reviewers agreed at journal 29 Jan, 2026 Reviewers invited by journal 28 Jan, 2026 Editor invited by journal 16 Jan, 2026 Editor assigned by journal 15 Jan, 2026 Submission checks completed at journal 15 Jan, 2026 First submitted to journal 14 Jan, 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8598273","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":587610575,"identity":"7cda6cc3-b4b7-4558-8be5-4ab2bc872662","order_by":0,"name":"Martin P. Nilsson","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYLCCBCBmYwczbUBcxgMENDA2gLUwgzlpYBMIawFTEC2HCWvRbT/7/MHDHQx5fMzsjz983HE+mp89geEwD0OdHC4tZmfSDRsSzzAUszHzmEnOPHM7d2bPA5CWw8Y4tRxIY2xIbGNIbGPmYWPmbbudu+EG2JYDiQ24tJx/BtPC/vgzb9u53P0QLXX1OLXcgNvCYCDN23Ygd4MEWAtzAk6H3XjGOCOxTQLkMKBf2pJzZ5x52HBwjsFhQ9wOS2P4+LPNJnF+ezswxNrscvvbkw8+eFNRJ4/LFiiQQOaAIsqAgIZRMApGwSgYBXgBAI6AV/Wx4Ug7AAAAAElFTkSuQmCC","orcid":"","institution":"Lund University","correspondingAuthor":true,"prefix":"","firstName":"Martin","middleName":"P.","lastName":"Nilsson","suffix":""},{"id":587610576,"identity":"a0913cab-aed4-482f-962b-5331d5598723","order_by":1,"name":"Jonas Scherman","email":"","orcid":"","institution":"Skåne University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jonas","middleName":"","lastName":"Scherman","suffix":""}],"badges":[],"createdAt":"2026-01-14 06:39:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8598273/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8598273/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102397751,"identity":"bd2b8024-45ab-4af5-9a16-e9d487bb8015","added_by":"auto","created_at":"2026-02-11 10:19:33","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1306760,"visible":true,"origin":"","legend":"\u003cp\u003eTitle: PET-CT images of lower inguinal lymph node metastases\u003c/p\u003e\n\u003cp\u003eLegend: Axial PET-CT images of the center of the most caudally located lower inguinal lymph node metastasis in each patient.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8598273/v1/84ea7121aaf19815e6b86aa9.jpg"},{"id":102398182,"identity":"f29c65a5-e482-420b-9b0c-fcce92e1cdef","added_by":"auto","created_at":"2026-02-11 10:21:39","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":272229,"visible":true,"origin":"","legend":"\u003cp\u003eTitle: Mapping of lower inguinal lymph node metastasis\u003c/p\u003e\n\u003cp\u003eLegend: Each dot represents a lower inguinal lymph node metastasis (\u003cem\u003en\u003c/em\u003e = 22) and is coded in the same color in Figure A and Figure B. The distance from the center of each lymph node metastasis to the closest border of the great saphenous vein (A) and the femoral vessels (B) is plotted, as well as a clock face direction in relation to these vessels (3:00 = medial; 6:00 = inferior; 9:00 = lateral; 12:00 = anterior).\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8598273/v1/ce922fd890a2552a6a2b600a.jpg"},{"id":102375290,"identity":"fa8b8295-4953-47f1-a17c-9dd3b0952e04","added_by":"auto","created_at":"2026-02-11 05:18:35","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":418253,"visible":true,"origin":"","legend":"\u003cp\u003eTitle: A potential route of tumor spread along the ano-inguinal lymphatic drainage\u003c/p\u003e\n\u003cp\u003eLegend: PET-CT of a patient with a large primary tumor and metastases in the ano-inguinal lymphatic drainage (A, B), the lower inguinal subregion (C), and the saphenofemoral subregion (D). The case illustrates a potential route of spread of tumor cells from the primary tumor to the inguinal region, where A and B (and possibly also C) are in-transit metastases rather than true lymph node metastases.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8598273/v1/d68caed27458f01712402dbe.jpg"},{"id":102399183,"identity":"fec3260b-1e69-4d4e-8710-eb981a2a3e15","added_by":"auto","created_at":"2026-02-11 10:33:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2620647,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8598273/v1/ad9913c6-5e11-48bb-8b39-50c357ed34e1.pdf"},{"id":102375289,"identity":"b12b3fc7-d57f-47a4-86ca-c8602a78aaf7","added_by":"auto","created_at":"2026-02-11 05:18:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":45158,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTableS1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8598273/v1/9295176adbccf531f9d7537c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Lower inguinal lymph node metastases in anal cancer: prevalence, predictors, and exact locations","fulltext":[{"header":"Background","content":"\u003cp\u003eMetastatic cells can spread from primary tumors in the lower pelvis to the inguinal region through lymph vessels collectively referred to as the superficial inguinal pathway or the ano-inguinal lymphatic drainage (AILD) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The most common inguinal sentinel node is the saphenofemoral node, located close to the saphenofemoral junction (SFJ), where the great saphenous vein (GSV) traverses the cribriform fascia, passes through the fossa ovalis, and enters the femoral vein [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, lymph node metastasis (LNM) can occur also in other parts of the inguinal region [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn many studies undertaken by surgeons the inguinal region has been meticulously subdivided into different parts, mainly been based on the level of the SFJ, the femoral vessels, and the deep fascia [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In contrast, articles written by radiation oncologist have generally been less detailed, which might have contributed to the lack of consensus in the radiation oncology community regarding the optimal borders of the elective clinical target volume (eCTV) [\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDapper et al analyzed the pattern of LNM in squamous cell carcinoma of the anus (anal cancer) and compared it with the major international contouring guidelines. All locoregional LNM located outside the eCTV were found in the inguinal region, most commonly in the lower part of it [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Motivated by this and with the aim of informing future contouring guidelines, we decided to undertake an analysis of lower inguinal LNM in anal cancer, defined as \u0026ge;\u0026thinsp;10 mm below the SFJ.\u003c/p\u003e \u003cp\u003eAs part of a previous study, we mapped LNM in anal cancer patients [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In the present study, we reanalyzed the study population specifically focusing on lower inguinal LNM. Predictors of metastatic spread to the lower inguinal region, as well as the exact location of lower inguinal LNM, were investigated.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eAll patients with anal cancer treated with radiotherapy at Sk\u0026aring;ne University Hospital during the years 2009 through 2017 were selected from an institutional database (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;203). Since Sk\u0026aring;ne University Hospital is the only hospital in the region treating anal cancer the cohort represents a consecutive population-based series. Most (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;190) had undergone baseline staging with [18F]-fluorodeoxyglucose positron emission tomography with computed tomography (PET-CT). The PET-CTs were done in the supine position with a slice thickness of 2.5-3 mm, either frog-legged or with a standard knee cushion. As part of a previous publication, these PET-CTs were retrospectively evaluated with the aim of assessing lymph nodes in a structured way [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Lymph nodes with an uptake above the mediastinal blood pool were considered PET-positive irrespective of size. In the following, PET-positive lymph nodes are denoted LNM. Each LNM was allocated to a nodal region and a nodal subregion. Specifically, the inguinal region was further subdivided into three subregions: the saphenofemoral subregion (within 10 mm above and below the SFJ, which was defined as the first CT-slice with visible fat separating the GSV and the femoral vein), the upper inguinal subregion (\u0026ge;\u0026thinsp;10 mm above the SFJ), and the lower inguinal subregion (\u0026ge;\u0026thinsp;10 mm below the SFJ) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe aim of the present study was to further analyze LNM in the lower inguinal subregion. To that end, the distance from the center of the most caudally located lower inguinal LNM to the SFJ was measured. Furthermore, the distance from the center of each lower inguinal LNM to the closest border of the GSV and the femoral vessels (vein or artery, whichever was closest), respectively, was measured in the axial plane. In case of branching of the great GSV, only the medial branch was considered. The clock face direction of each lower inguinal LNM in relation to vessels in the right groin (left medial converted to right medial) was also noted. In-transit metastases along the AILD in the labia major/scrotum and the subcutaneous tissue of the medial thigh were not counted as inguinal LNM but were reported.\u003c/p\u003e \u003cp\u003eDescriptive statistics were used to summarize the characteristics of the study population. Continuous variables were reported with means or medians and value ranges. The Mann-Whitney U test was used to compare continous variables. Categorical variables were compared using crosstabs and statistical significance was assessed with the chi-squared test or Fisher\u0026rsquo;s exact test, as appropriate. Statistical analyses were conducted using SPSS version 30.0. All significance tests were 2-sided, and \u003cem\u003eP\u003c/em\u003e values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e was based on screenshots of diagnostic images and edited using Inkscape version 1.3.2. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e was done in RStudio version 2025.09.2.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003ePatient and tumor characteristics are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age was 65.1 years and 79.5% were female. Distant metastasis at diagnosis was seen in 7.9%. As previously reported, LNM were identified in 54.2% (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;103), and inguinal LNM in 39.5% (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;75) of the patients. Inguinal LNM were unilateral in 47 patients and bilateral in 28 patients, corresponding to 103 inguinal regions with a total of 182 pathologic lymph nodes; 119 located in the saphenofemoral subregion, 41 in the upper inguinal subregion, and 22 in the lower inguinal subregion.\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\u003ePatient and tumor characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll patients with PET-CT, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;190 (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients with lymph node metastasis on PET-CT, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;103 (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at diagnosis, mean (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.7\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\u003e151 (79.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81 (78.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size, median (mm; range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (4-150)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (4-150)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerianal extention\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99 (52.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (59.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT stage\u003csup\u003eb\u003c/sup\u003e\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86 (45.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (35.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (30.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (31.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegional or CI/PA lymph node metastasis\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103 (54.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInguinal lymph node metastasis\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 (39.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (72.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistant metastasis\u003csup\u003ea,d\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (13.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAbbreviations: CI/PA, common iliac or para-aortic; PET-CT, [18F]-fluorodeoxyglucose positron emission tomography with computed tomography\u003c/p\u003e \u003cp\u003ewith computed tomography\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e Extension of the primary tumor outside the anal verge\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003eb\u003c/sup\u003e TNM8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003ec\u003c/sup\u003e Deauville score 3\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003csup\u003ed\u003c/sup\u003e Includes common iliac and para-aortic lymph node metastasis\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003ePrevalence of lower inguinal LNM\u003c/h3\u003e\n\u003cp\u003eOut of 190 patients, 16 (8.4%) had lower inguinal LNM, of whom 2 bilateral, corresponding to 18 lower inguinal subregions with a total of 22 pathologic lymph nodes. Thus, 18 of 103 (17.5%) inguinal regions with LNM harbored LNM in the lower inguinal subregion. Axial PET-CT images of the center of the most caudally located lower inguinal LNM in each individual patient are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In addition to LNM in the lower inguinal subregion, 5 also harbored LNM in the upper inguinal subregion and 16 in the saphenofemoral subregion. Accordingly, only 2 inguinal regions had lower inguinal LNM without the synchronous occurrence of saphenofemoral LNM.\u003c/p\u003e\n\u003ch3\u003eExact location of lower inguinal LNM\u003c/h3\u003e\n\u003cp\u003eThe exact location of each lower inguinal LNM in relation to the GSV and the femoral vessels is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. A clock face of the right groin shows that 59% were medial (1:00\u0026ndash;4:00) and 36% were lateral (7:00\u0026ndash;11:00) to the GSV. In contrast, no LNM were located lateral or posterior to the femoral vessels.\u003c/p\u003e \u003cp\u003eFor every lower inguinal LNM the distance was shorter to the GSV vein (median 7 mm; range 4\u0026ndash;19) than to the femoral vessels (median 21 mm; range 9\u0026ndash;37) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). Only one LNM was located more than 10 mm medial to the GSV.\u003c/p\u003e\n\u003ch3\u003eDistance from the saphenofemoral junction\u003c/h3\u003e\n\u003cp\u003eThe center of the most caudally located lower inguinal LNM in each inguinal region was located 10\u0026ndash;43 mm below the SFJ (median 18 mm; Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). One patient in this cohort had in-transit metastases in the AILD, not counted as lower inguinal LNM. The center of the most caudal AILD metastasis, located in labia major, was 60 mm below the SFJ (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Lower inguinal LNM were not more caudal in men (median 15 mm below the SFJ; range 10\u0026ndash;25) than in women (median 20 mm below the SFJ; range 10\u0026ndash;43) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.11).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows what proportion of lower inguinal LNM that are covered by a distal margin of 2, 3 and 4 cm from the SFJ, respectively. A distal margin of 2.5 cm from the SFJ covered all lower inguinal LNM in 97 of 103 (95%) inguinal regions with LNM and in 375 of 380 (98.7%) inguinal regions in all patients.\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\u003eProportion of inguinal regions with all lower inguinal LNM covered across different subgroups of patients, using different distal margins\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistal margin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInguinal regions in all patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eInguinal regions with LNM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eInguinal regions with lower inguinal LNM\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2 cm distal to the SFJ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e372 of 380 (97.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95 of 103 (92.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 of 18 (55.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 cm distal to the SFJ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e377 of 380 (99.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 of 103 (97.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 of 18 (83.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4 cm distal to the SFJ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e378 of 380 (99.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101 of 103 (98.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 of 18 (88.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAbbreviations: LNM, lymph node metastasis; SFJ, saphenofemoral junction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003ePredictors of lower inguinal LNM\u003c/h3\u003e\n\u003cp\u003eCompared to all other patients with LNM (Table\u0026nbsp;3a), as well as compared to patients with LNM in the saphenofemoral or upper inguinal subregions (Table\u0026nbsp;3b), patients with lower inguinal LNM had larger tumors and more often stage T4 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Perianal tumor extension was non-significantly more common among patients with lower inguinal LNM compared to all other patients with LNM (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.06) but not compared to patients with LNM in the saphenofemoral or upper inguinal subregions (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.00).\u003c/p\u003e\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"496\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"bottom\" style=\"width: 432px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3a\u003c/strong\u003e. Lower inguinal LNM among all patients with LNM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 250px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"bottom\" style=\"width: 246px;\"\u003e\n \u003cp\u003eLower inguinal LNM\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 250px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003eNo, \u003cem\u003en\u003c/em\u003e = 87 (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 93px;\"\u003e\n \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e = 16 (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 250px;\"\u003e\n \u003cp\u003ePrimary tumor size, median (mm; range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e50 (4-150)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 93px;\"\u003e\n \u003cp\u003e70 (52-100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.002\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 250px;\"\u003e\n \u003cp\u003eT stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 250px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; T1-3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e64 (90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 93px;\"\u003e\n \u003cp\u003e7 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 250px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; T4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e23 (72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 93px;\"\u003e\n \u003cp\u003e9 (28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 250px;\"\u003e\n \u003cp\u003ePerianal extension of the primary tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 250px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e39 (93%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 93px;\"\u003e\n \u003cp\u003e3 (7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 250px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e48 (79%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 93px;\"\u003e\n \u003cp\u003e13 (21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 250px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 250px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e69 (85%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 93px;\"\u003e\n \u003cp\u003e12 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 250px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e18 (82%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 93px;\"\u003e\n \u003cp\u003e4 (18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 339px;\"\u003e\n \u003cp\u003eAbbreviations: LNM, lymph node metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 93px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"484\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"bottom\" style=\"width: 420px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3b\u003c/strong\u003e. Lower inguinal LNM among patients with inguinal LNM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 242px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"bottom\" style=\"width: 242px;\"\u003e\n \u003cp\u003eLower inguinal LNM\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003eNo, \u003cem\u003en\u003c/em\u003e = \u0026nbsp;59 (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e = 16 (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 242px;\"\u003e\n \u003cp\u003ePrimary tumor size, median (mm; range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e60 (4-150)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003e70 (52-100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 242px;\"\u003e\n \u003cp\u003eT stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; T1-3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e44 (86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003e7 (14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; T4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e15 (63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003e9 (37%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 242px;\"\u003e\n \u003cp\u003ePerianal extension of the primary tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e14 (82%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3 (18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e45 (78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003e13 (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 242px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e44 (79%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003e12 (21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e15 (79%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003e4 (21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 330px;\"\u003e\n \u003cp\u003eAbbreviations: LNM, lymph node metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 64px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this cohort of unselected anal cancer patients the prevalence of lower inguinal LNM was 8.4%. In 16 of 18 groins with lower inguinal LNM the saphenofemoral node was also metastatic, but two patients had lower inguinal LNM without a saphenofemoral LNM, indicating that in rare cases there can be a direct spread of tumor cells to lower inguinal lymph nodes. Leijte et al found no lower inguinal sentinel lymph nodes in anal cancer [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], but larger studies in penile cancer and vulvar cancer have reported that lower inguinal sentinel nodes and isolated metastases do occur in a minority of the patients [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe results of our study clearly showed that lower inguinal LNM follow the GSV rather than the femoral vessels. In fact, not a single lower inguinal LNM was close to the femoral vessels, suggesting that LNM in anal cancer are rare, or even absent, posterior to the deep fascia at \u0026ge;\u0026thinsp;10 mm below the SFJ. This is supported by Lengele et al who summarized the anatomical literature and concluded that the lowest deep inguinal node, if present, is situated against the femoral vein just below the SFJ [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Consequently, instructions for the contouring of the lower inguinal subregion should be based on other anatomical landmarks than the femoral vessels.\u003c/p\u003e \u003cp\u003eOut of the 22 lower inguinal LNM in our study, only one was located more than 10 mm medial to the GSV. In that patient, multiple in-transit metastases in the AILD were also present (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). It is possible that the LNM classified as \u0026lsquo;lower inguinal\u0026rsquo; was in fact also an in-transit AILD metastasis, rather than a true LNM. Anyway, a medial margin of 7\u0026ndash;8 mm from the border of the GSV seems sufficient to cover most lower inguinal LNM in anal cancer, which is in line with the recommendation of 10 mm medial to the center of the GSV proposed by Chang et al in a recent and informative study of inguinal LNM in 181 patients with various pelvic malignancies (34 anal cancer cases) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe inferior border of the eCTV varies between different contemporary inguinal contouring guidelines for anal cancer. Most of them use bony landmarks, such as the lower edge of the lesser trochanter [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] or the ischial tuberosity [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Although more research is needed to define the optimal landmark, we believe that the most appropriate inferior border of the eCTV is defined by a caudal margin from the SFJ, which is also recommended by the RTOG [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The saphenofemoral node, located close to the SFJ, is a central component of the superficial inguinal pathway and the SFJ should therefore be more representative of lymph node topographic anatomy than any bony landmark. One limitation when comparing the results of different studies based on cross sectional imaging is that most authors have not stated a clear definition of the SFJ. We defined the SFJ as the first axial CT-slice with visible fat separating the GSV and the femoral vein.\u003c/p\u003e \u003cp\u003eIn our study, a caudal margin of 2.5 cm below the SFJ covered all lower inguinal LNM in 95% of the inguinal regions with LNM. An increased likelihood of lower inguinal LNM was seen in larger tumors and in T4 tumors, which might open for an individualization of the eCTV: for patients with T1-2 tumors a smaller margin below the SFJ might suffice, whereas for patients with advanced tumors invading the lower anal canal or perianal area and for patients with LNM in the saphenofemoral subregion a larger caudal margin could be more appropriate. Further research is needed and should be aiming at presenting data which can constitute a foundation for an individualization of the eCTV.\u003c/p\u003e \u003cp\u003eThere are limitations to our study. First, we measured the distance from the center of LNM to vessels, which is not perfect in case of displacement of the center caused by enlargement or anisotropic growth. For enlarged lymph nodes abutting vessels the methodology would likely overestimate rather than underestimate the distance between vessels and nonenlarged micrometastatic lymph nodes. Second, using PET-CT instead of pathological verification entails a risk of both false negative and false positive findings. Third, despite (to the best of our knowledge) being the largest anal cancer lymph node mapping study to date, the study cohort is still relatively small, and the results should be replicated by others before any firm conclusions can be drawn.\u003c/p\u003e \u003cp\u003eTo conclude, the results of our study indicate that lower inguinal LNM occur in 8.4% of unselected anal cancer patients, with higher frequencies in patients with stage T4 or large primary tumors. In the lower inguinal subregion LNM follow the GSV rather than the femoral vessels. To capture the different anatomical compartments of the groin future contouring guidelines should present separate recommendations for different inguinal subregions. Also, they should be aiming at providing individual risk-adapted recommendations rather than a \u0026lsquo;one size fits all\u0026rsquo;.\u003c/p\u003e"},{"header":"Abbreviations","content":"AILD, ano-inguinal lymphatic drainage; eCTV, elective clinical target volume; GSV, great saphenous vein; LNM, lymph node metastasis; PET-CT, [18F]-fluorodeoxyglucose positron emission tomography with computed tomography; SFJ, saphenofemoral junction."},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003eThe study was approved by the Regional Ethical Review Board in Lund (Dnr 2013/742) and by the Swedish Ethical Review Authority (Dnr 2019/02669). The need for informed consent was waived given the retrospective nature of the study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eSupplementary Table S1\u003c/h2\u003e \u003cp\u003e. Lower inguinal lymph node metastasis in relation to vessels.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe work was funded by The Swedish Cancer Society (Grant number 23-2639).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eMPN conceived of the study and collected the clinical data. MPN remeasured distances to anatomical landmarks (which had previously been done by radiologist Anna Frennered). MPN carried out the statistical analyses. MPN and JS analyzed and interpreted the results. MNL and JS drafted the manuscript and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe present data is summarized in this paper. The complete dataset can be retrieved from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDapper H, Habl G, Hirche C, M\u0026uuml;nch S, Oechsner M, Mayinger M, Sauter C, Combs SE, Habermehl D. Dosimetric quantification of the incidental irradiation of the 'true' (deep) ano-inguinal lymphatic drainage of anal cancer patients not described in conventional contouring guidelines. Acta Oncol. 2018;57(6):825\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePa\u0026ntilde;o B, Sebasti\u0026agrave; C, Bu\u0026ntilde;esch L, Mestres J, Salvador R, Mac\u0026iacute;as NG, Nicolau C. Pathways of lymphatic spread in male urogenital pelvic malignancies. Radiographics. 2011;31(1):135\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeijte JA, Vald\u0026eacute;s Olmos RA, Nieweg OE, Horenblas S. Anatomical mapping of lymphatic drainage in penile carcinoma with SPECT-CT: implications for the extent of inguinal lymph node dissection. Eur Urol. 2008;54(4):885\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollarino A, Donswijk ML, van Driel WJ, Stokkel MP, Vald\u0026eacute;s Olmos RA. The use of SPECT/CT for anatomical mapping of lymphatic drainage in vulvar cancer: possible implications for the extent of inguinal lymph node dissection. Eur J Nucl Med Mol Imaging. 2015;42(13):2064\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrennered A, Scherman J, Buchwald P, Johnsson A, Sartor H, Zackrisson S, Tr\u0026auml;g\u0026aring;rdh E, Nilsson MP. Patterns of pathologic lymph nodes in anal cancer: a PET-CT-based analysis with implications for radiotherapy treatment volumes. BMC Cancer. 2021;21(1):447.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarda AE, Navin PJ, Merrell KW, Martenson JA, Neben Wittich MA, Haddock MG, Sio TT, Rule WG, Ashman JB, Sheedy SP, et al. Patterns of inguinal lymph node metastases in anal canal cancer and recommendations for elective clinical target volume (CTV) delineation. Radiother Oncol. 2020;149:128\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMittal R, Krishnatry R, Maitre P, Murthy V. Recommendations and Clinical Validation of Inguinal Clinical Target Volume Delineation in Penile Cancer. Int J Radiat Oncol Biol Phys. 2021;111(3):741\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHan JL, Qi YG, Liu JL, Yan X, Zhang WC, Yuan L, Hao XZ, Song JB, Li SJ. Investigation of the distribution of inguinal lymph nodes and delineation of the inguinal clinical target volume using (18)F-FDG PET/CT. BMC Cancer. 2024;24(1):1254.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOmorphos S, Saad Z, Kirkham A, Nigam R, Malone P, Bomanji J, Muneer A. Zonal mapping of sentinel lymph nodes in penile cancer patients using fused SPECT/CT imaging and lymphoscintigraphy. \u003cem\u003eUrol Oncol\u003c/em\u003e 2018, 36(12):530.e531-530.e536.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTan X, Cai T, Wang Y, Wu Z, Zhou Q, Guo S, Li J, Yuan G, Liu Z, Li Z, et al. Regional lymph node mapping in patients with penile cancer undergoing radical inguinal lymph node dissection - a retrospective cohort study. Int J Surg. 2024;110(5):2865\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUK national guidance. for volumetricmodulated arc therapy (VMAT) or intensity-modulated radiotherapy (IMRT) in anal cancer. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.rcr.ac.uk/media/tahena34/rcr-vmat-imrt-anal-guidance-2024-v3.pdf\u003c/span\u003e\u003cspan address=\"https://www.rcr.ac.uk/media/tahena34/rcr-vmat-imrt-anal-guidance-2024-v3.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed on Jan 7, 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDamico N, Meyer J, Das P, Murphy J, Miller E, Koontz B, Hall W, McBride M, Pereira G, Catalano P, et al. ECOG-ACRIN Guideline for Contouring and Treatment of Early Stage Anal Cancer Using IMRT/IGRT. Pract Radiat Oncol. 2022;12(4):335\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMyerson RJ, Garofalo MC, El Naqa I, Abrams RA, Apte A, Bosch WR, Das P, Gunderson LL, Hong TS, Kim JJ, et al. Elective clinical target volumes for conformal therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring atlas. Int J Radiat Oncol Biol Phys. 2009;74(3):824\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNg M, Leong T, Chander S, Chu J, Kneebone A, Carroll S, Wiltshire K, Ngan S, Kachnic L. Australasian Gastrointestinal Trials Group (AGITG) contouring atlas and planning guidelines for intensity-modulated radiotherapy in anal cancer. Int J Radiat Oncol Biol Phys. 2012;83(5):1455\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNilsson MP, Undseth C, Albertsson P, Eidem M, Havelund BM, Johannsson J, Johnsson A, Radu C, Serup-Hansen E, Spindler KL, et al. Nordic anal cancer (NOAC) group consensus guidelines for risk-adapted delineation of the elective clinical target volume in anal cancer. Acta Oncol. 2023;62(8):897\u0026ndash;906.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDapper H, Schiller K, M\u0026uuml;nch S, Peeken JC, Borm K, Weber W, Combs SE. Have we achieved adequate recommendations for target volume definitions in anal cancer? A PET imaging based patterns of failure analysis in the context of established contouring guidelines. BMC Cancer. 2019;19(1):742.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLengel\u0026eacute; B, Scalliet P. Anatomical bases for the radiological delineation of lymph node areas. Part III: Pelvis and lower limbs. Radiother Oncol. 2009;92(1):22\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang Y, Li G, Yang Z, Han G, Li X, Zhao Y, Yang Q, Wu G, Yang K, Zhao Y. Inguinal nodal clinical target volume delineation based on analysis of anatomical locations of normal and metastatic lymph nodes in pelvic malignant tumors. Radiother Oncol. 2023;183:109634.\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":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Anal cancer, anal carcinoma, inguinal, lymph node, metastasis, contouring, elective clinical target volume","lastPublishedDoi":"10.21203/rs.3.rs-8598273/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8598273/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIn anal caner, the lower inguinal subregion is the most common site of regional lymph node metastases (LNM) occurring outside the borders of the major contouring guidelines. With the aim of informing future contouring guidelines, the present study investigated the exact locations and predictors of lower inguinal LNM.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eBaseline FDG-PET-CTs from a consecutive population-based series of anal cancer patients (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;190) were used to identify LNM in the lower inguinal subregion, defined as \u0026ge;\u0026thinsp;10 mm below the saphenofemoral junction (SFJ). Lymph nodes with an FDG uptake above the mediastinal blood pool were considered metastatic irrespective of size. The distances from the center of each LNM to the SFJ, the great saphenous vein (GSV), and the femoral vessels were measured. The characteristics of patients with lower inguinal LNM were compared with other patients using non-parametric tests.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eLower inguinal LNM were identified in 8.4% of the patients. For every lower inguinal LNM the distance was shorter to the GSV vein (median 7 mm; range 4\u0026ndash;19) compared to the femoral vessels (median 21 mm; range 9\u0026ndash;37). Only one lower inguinal LNM was located more than 10 mm medial to the GSV. A distal margin of 2.5 cm from the SFJ covered all lower inguinal LNM in 97 of 103 (95%) inguinal regions with LNM and in 375 of 380 (98.7%) inguinal regions in all patients. Patients with lower inguinal LNM had larger tumors and more often stage T4, which might open for an individualization of the inferior border of the elective clinical target volume (eCTV).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn the lower inguinal subregion LNM follow the GSV rather than the femoral vessels. To capture the different anatomical compartments of the inguinal region future contouring guidelines should present separate recommendations for different inguinal subregions. In addition, they should be aiming at providing individual risk-adapted recommendations rather than a \u0026lsquo;one size fits all\u0026rsquo;.\u003c/p\u003e","manuscriptTitle":"Lower inguinal lymph node metastases in anal cancer: prevalence, predictors, and exact locations","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-11 05:18:31","doi":"10.21203/rs.3.rs-8598273/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-03T08:07:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-21T18:55:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-10T09:54:30+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-01T17:14:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-27T06:06:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"141073089845486272235469709255685341328","date":"2026-02-20T07:44:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"211602614727140800998419555757702803830","date":"2026-02-19T09:42:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"75915997999676444172507739371910565936","date":"2026-02-19T06:46:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"7875542620914427755171171821720049406","date":"2026-02-19T05:44:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-10T12:29:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"131614951354205495625030488348707021738","date":"2026-01-31T07:16:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"99144880466166711063344600182384316124","date":"2026-01-29T08:36:18+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-29T04:30:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-16T06:08:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-15T11:06:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-15T11:05:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2026-01-14T06:30:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"09bea4eb-ad56-4ca0-822a-a10c9bfda2a5","owner":[],"postedDate":"February 11th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T09:38:38+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-11 05:18:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8598273","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8598273","identity":"rs-8598273","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}