The aim of this study was to determine whether the presence and extent of lymphovascular invasion (LVI) is prognostic in surgical stage I cervical squamous cell carcinoma (SCC). All available tumour slides and/or paraffin blocks from 426 patients with stage I cervical SCC treated surgically with curative intent were collected from 18 institutions and retrospectively analysed. Presence and extent of LVI (focal <5 spaces, extensive ≥5 spaces) were assessed on scanning magnification in large haematoxylin and eosin slide sets in 366 cases. Progression-free survival (PFS) was calculated as the time from surgery to first progression or death or last follow-up, whichever occurred first. Overall survival (OS) was defined as the time from surgery to death or last follow-up. Clinicopathological and statistical analyses were performed on 97 patients with the International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IA and 329 patients with stage IB SCC of the cervix. LVI, both focal and extensive, was more frequent in stage IB than in stage IA (p<0.001). Patients with stage IB carcinomas with extensive LVI had worse PFS [hazard ratio (HR) 2.86; 95% confidence interval (CI) 1.49, 5.49; p=0.005] and OS (HR 2.88; 95% CI 1.38, 6.02; p=0.012) than those with focal or no LVI. In stage IA, in contrast, the presence and extent of LVI did not associate with PFS (p=0.926) or OS. Extensive LVI was not statistically correlated with PFS and OS in substages IA1, IA2 or IB2. PFS (HR 3.7; 95% CI 1.61, 8.46; p<0.001) and OS (HR 4.18; 95% CI 1.58, 11.04; p=0.002) in stage IB1, and PFS (HR 7.78; 95% CI 0.87, 69.82; p=0.039) in stage IB3 were diminished in the presence of extensive LVI. In conclusion, in patients with FIGO stage I cervical SCC, the presence and extent of LVI has prognostic significance in stage IB carcinoma, and quantifying LVI is recommended.

Department of Gynaecology Obstetrics and Neonatology General University Hospital Prague 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Pathology 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Pathology A C Camargo Cancer Center Sao Paulo Brazil

Department of Pathology and Laboratory Medicine Emory University School of Medicine Atlanta USA

Department of Pathology Cleveland Clinic Cleveland USA

Department of Pathology Hospital Universitari de Bellvitge IDIBELL Barcelona Spain

Department of Pathology Laboratory Medicine Program University Health Network Toronto Canada

Department of Pathology Massachusetts General Hospital Boston MA USA

Department of Pathology Memorial Sloan Kettering Cancer Center New York NY USA

Department of Pathology Oncologic Institute Lisbon Portugal

Department of Pathology Sahlgrenska University Hospital Gothenburg Sweden

Department of Pathology Universita degli Studi di Messina Italy

Department of Pathology University of California San Diego USA

Department of Pathology University of Chicago Chicago IL USA

Department of Pathology University of Medicine Pharmacy Science and Technology 'George E Palade' of Targu Mures Targu Mures Romania

Department of Pathology University of Michigan Detroit MI USA

Department of Pathology Vancouver General Hospital Vancouver BC Canada

Department of Pathology Wayne University Detroit MI USA

Department of Surgical Oncology A C Camargo Cancer Center Brazil

Jikei University School of Medicine Tokyo Japan

Ospedale Sacro Cuore Don Calabria Negrar Italy

Regional Institute of Oncology Iasi Romania

Zobrazit více v PubMed

Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of cancer incidence and mortality for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68:394–424 PubMed

WHO Classification of Tumours Editorial Board. WHO Classification of Tumours, 5th Edition. Female Genital Tumours. International Agency for Research on Cancer. 2020

Siegel RL, Miller KD, Fuchs HE et al. Cancer statistics. CA Cancer J Clin 2022; 72 (1): 7–33 PubMed

Bhatla N, Berek JS, Fredes MC, et al. Revised FIGO staging for carcinoma of the cervix uteri, Int. J. Gynaecol. Obstet 2019; 145 (1): 129–135 PubMed

Abu-Rustum N, Yashar C, Arend R. NCCN Clinical Practice Guidelines in Oncology. Cervical Cancer; version 1. 2024. www.nccn.org/patients

Cibula D, Raspollini MR, Planchamp F et al. ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer – Update 2023. Virchows Arch 2023; 482: 935–966 PubMed PMC

Cibula D, Potter R, Planchamp F et al. The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology guidelines for the management of patients with cervical cancer, Radiother Oncol 2018; 127 (3): 404–416 PubMed

Praiss A, Allison D, Tessier-Cloutier B et al. : Extensive versus focal lymphovascular invasion in squamous cell carcinoma of the cervix. A comprehensive international, multicentric retrospective clinicopathologic study. Gynecol Oncol 2023; 176: 147–154 PubMed PMC

Sedlis A, Bundy BN, Rotman MZ,et al. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterecomy and pelvic lymphadenectomy: A Gynecologic Oncology Group Study, Gynecol. Oncol. 1999; 73 (2): 177–183 PubMed

Delgado G, Bundy BN, Fowler WC, et al. A prospective surgical pathological study of stage I squamous carcinoma of the cervix: a Gynecologic Oncology Group Study, Gynecol. Oncol 1989; 35 (3): 314–320 PubMed

Delgado G, Bundy B, Zaino R, et al. Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study, Gynecol. Oncol 1990; 38 (3): 352–357 PubMed

Levinson K, Beavis AL, Purdy C et al. Beyond Sedlis-A novel histology-specific nomogram for predicting cervical cancer recurrence risk: an NRG/GOG ancillary analysis, Gynecol. Oncol 2021; 162 (3): 532–538 PubMed PMC

Alvarado-Cabrero I, Roma AA, Park KJ, et al. Factors predicting pelvic lymph node metastasis, relapse, and disease outcome in pattern C endocervical adenocarcinomas, Int. J. Gynecol. Pathol 2017; 36 (5): 476–485 PubMed

Zaino RJ, Ward S, Delgado B, et al. Histopathologic predictors of the behavior of surgically treated stage IB squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study, Cancer 1992); 69: 1750–1758 PubMed

Stolnicu S, Hoang L, Almadani N, et al. Clinical correlation of lymphovascular invasion and Silva pattern of invasion in early-stage endocervical adenocarcinoma: proposed binary Silva classification system. Pathology 2022; 54: 548–554 PubMed PMC

Bosse T, Peters EE, Creutzberg CL, et al. Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer—a pooled analysis of PORTEC 1 and 2 trials. Eur J Cancer 2015; 51:1742–50 PubMed

Peters EM, Leon-Castillo A, Hoddall E et al. Substantial Lymphovascular Space Invasion Is an Adverse Prognostic Factor in High-Risk Endometrial Cancer. Int J Gynecol Pathol 2021; 41: 227–234 PubMed

Pifer PM, Bhargava R, Patel AK et al. Is the risk of substantial LVSI in stage I endometrial cancer similar to PORTEC in the North American population? A single institution study. Gynecol Oncol 2020, 159: 23–29 PubMed

Berek JS, Matias-Guiu X, Creutzberh C et al. FIGO staging in endometrial cancer: 2023. Int J Gynecol Obstet, 2023; 162: 383–395 PubMed

Abu-Rustum N, Yashar C, Arend R et al. NCCN Clinical practice guidelines in oncology, Uterine neoplasms, version 1.2023. www.nccn.org PubMed

Concin N, Matias-Guiu X, Vergote I et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial cancer. Int J Gynecol Cancer 2021, 31: 12–39 PubMed

Heller G, Venkatraman ES. Resampling procedures to compare two survival distributions in the presence of right censored data. Biometrics 1996; 52:1204–1213

Stolnicu S, Allison D, Praiss AM et al. Incidence and clinicopathologic characteristics of Human Papillomavirus-independent invasive squamous cell carcinomas of the cervix: a morphologic, immunohistochemical and Human Papilloma-virologic study of 670 cases. Am J Surg Pathol 2023; 47: 1376–1389 PubMed PMC

Briet JM, Hollema H, Reesink N, et al. Lymphvascular space involvement: an independent prognostic factor in endometrial cancer. Gynecol Oncol 2005; 96: 799–804 PubMed

Qian Y, Pollom EL, Nwachukwu C, et al. Extent of lymphovascular space invasion may predict lymph node metastasis in uterine serous carcinoma. Gynecol Oncol 2017; 147: 24–9 PubMed PMC

Keys HM, Roberts JA, Brunetto VL, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 2004; 92: 744–51 PubMed

Morrow CP, Bundy BN, Kurman RJ, et al. Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol 1991; 40: 55–65 PubMed

Guntupalli SR, Zighelboim I, Kizer NT, et al. Lymphovascular space invasion is an independent risk factor for nodal disease and poor outcomes in endometrioid endometrial cancer. Gynecol Oncol 2012; 124:31–5 PubMed PMC

Stalberg K, Bjurberg M, Borgfeldt C, et al. Lymphovascular space invasion as a predictive factor for lymph node metastases and survival in endometrioid endometrial cancer—a Swedish Gynecologic Cancer Group (SweGCG) study. Acta Oncol 2019; 58:1628–33 PubMed

Park KJ, Selinger CI, Alvarado-Cabrero I et al. , Dataset for the reporting of carcinoma of the cervix: recommendations from the international collaboration on cancer reporting (ICCR), Int. J. Gynecol. Pathol 2022; 41 (Suppl. 1): S64–S89 PubMed

Matias-Guiu X, Selinger CI, Anderson L et al. Data set for reporting of endometrial cancer: Recommendations from the International Collaboration on Cancer Reporting (ICCR). Int J Gynecol Pathol 2022; 41 (Suppl 1): S90–S118 PubMed

Singh N, Hirschowitz L, Zaino R et al. : Pathologic prognostic factors in endometrial carcinoma (Other than tumor type and grade). Int J Gynecol Pathol 2019, 38 (Suppl 1): S93–S113 PubMed PMC

Protocol for the Examination of Specimens From Patients With Carcinoma and Carcinosarcoma of the Endometrium; 2020; https://documents.cap.org/protocols/cp-femalereproductive-endometrium-20-4102.pdf

Margolis B, Cagle-Colon K, Cgen L et al. Prognostic significance of lymphovascular space invasion for stage IA1 and IA2 cervical cancer. Int J Gynecol Cancer 2020; 30(6): 735–743 PubMed