First Analysis of the Incidence of Serous Tubal Intraepithelial Carcinoma (STIC) in Germany – Evaluation of the Cancer Registry of the Federal State of Rhineland-Palatinate from 2016 to 2023

Abstract

Introduction

Serous tubal intraepithelial carcinomas (STIC) are classified as precursor lesions of high-grade serous carcinomas (HGSC) in women. STIC are rare and their incidence, prognosis and therapy remain unclear. Since 2021, all cases of isolated STIC in Germany must be reported, which means that all STICs in the German federal state of the Rhineland-Palatine (RLP) are available for evaluation.

Material and Methods

A systematic search of the pathology reports in the RLP cancer registry was carried out for the period 01/2016–12/2023 using keywords related to STIC, and the results of the search were evaluated.

Results

382 pathology reports were identified as relevant and screened. A total of seven patients with isolated STIC were reported to the RLP registry in the years 2020–2022. This corresponds to 0.014% of all reported cases of cancer in women in RLP in this period. Six patients had a diagnosis of isolated STIC, identified during risk-reducing salpingo-oophorectomy (RRSO). The mean patient age at the time of RRSO was 60.29 (± 7.09) years. RRSO was carried out on average 9.38 (± 6.75) years after a primary diagnosis of breast cancer/DCIS in five patients. No HGSC was reported for any of the patients with isolated STIC in the follow-up period until 01/2024. 43 synchronous STICs were reported for the period from 01/2016 to 12/2023.

Conclusion

2–3 diagnoses of isolated STIC were recorded annually in RLP in the years 2020–2022. To date, there have been no reports of HGSC in these patients. In the future, the systematic recording of STICs will be expanded to include the cancer registries of other federal states of Germany and it will be possible to obtain valid data on the incidence of STIC in Germany. The collected data will also provide the basic information for a national STIC registry.

Keywords

STIC - serous tubal intraepithelial carcinoma - cancer registry - incidence - STIC registry - Rhineland-Palatinate

Publication History

Received: 22 October 2024

Accepted after revision: 09 March 2025

Article published online:
15 May 2025

• References/Literatur

• 1 Kurman RJ, Shih IeM. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol 2010; 34: 433-443
• 2 Piek JM, van Diest PJ, Zweemer RP. et al. Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer. J Pathol 2001; 195: 451-456
• 3 Medeiros F, Muto MG, Lee Y. et al. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol 2006; 30: 230-236
• 4 Shaw PA, Rouzbahman M, Pizer ES. et al. Candidate serous cancer precursors in fallopian tube epithelium of BRCA1/2 mutation carriers. Mod Pathol 2009; 22: 1133-1138
• 5 Jarboe EA, Folkins AK, Drapkin R. et al. Tubal and ovarian pathways to pelvic epithelial cancer: a pathological perspective. Histopathology 2008; 53: 127-138
• 6 Crum CP, Drapkin R, Miron A. et al. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol 2007; 19: 3-9
• 7 Shih IM, Wang Y, Wang TL. The Origin of Ovarian Cancer Species and Precancerous Landscape. Am J Pathol 2021; 191: 26-39
• 8 Bertozzi S, Londero AP, Xholli A. et al. Risk-Reducing Breast and Gynecological Surgery for BRCA Mutation Carriers: A Narrative Review. J Clin Med 2023; 12: 1422
• 9 Eleje GU, Eke AC, Ezebialu IU. et al. Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations. Cochrane Database Syst Rev 2018; (08) CD012464
• 10 Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 2009; 101: 80-87
• 11 Li HX, Lu ZH, Shen K. et al. Advances in serous tubal intraepithelial carcinoma: correlation with high grade serous carcinoma and ovarian carcinogenesis. Int J Clin Exp Pathol 2014; 7: 848-857
• 12 Powell CB, Kenley E, Chen LM. et al. Risk-reducing salpingo-oophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy. J Clin Oncol 2005; 23: 127-132
• 13 Finch A, Shaw P, Rosen B. et al. Clinical and pathologic findings of prophylactic salpingo-oophorectomies in 159 BRCA1 and BRCA2 carriers. Gynecol Oncol 2006; 100: 58-64
• 14 Wethington SL, Park KJ, Soslow RA. et al. Clinical outcome of isolated serous tubal intraepithelial carcinomas (STIC). Int J Gynecol Cancer 2013; 23: 1603-1611
• 15 Saccardi C, Zovato S, Spagnol G. et al. Efficacy of risk-reducing salpingo-oophorectomy in BRCA1–2 variants and clinical outcomes of follow-up in patients with isolated serous tubal intraepithelial carcinoma (STIC). Gynecol Oncol 2021; 163: 364-370
• 16 Linz VC, Lowe A, van der Ven J. et al. Incidence of pelvic high-grade serous carcinoma after isolated STIC diagnosis: A systematic review of the literature. Front Oncol 2022; 12: 951292
• 17 Steenbeek MP, van Bommel MHD, Bulten J. et al. Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis. J Clin Oncol 2022; 40: 1879-1891
• 18 Chay WY, McCluggage WG, Lee CH. et al. Outcomes of Incidental Fallopian Tube High-Grade Serous Carcinoma and Serous Tubal Intraepithelial Carcinoma in Women at Low Risk of Hereditary Breast and Ovarian Cancer. Int J Gynecol Cancer 2016; 26: 431-436
• 19 Blok F, Dasgupta S, Dinjens WNM. et al. Retrospective study of a 16year cohort of BRCA1 and BRCA2 carriers presenting for RRSO: Prevalence of invasive and in-situ carcinoma, with follow-up. Gynecol Oncol 2019; 153: 326-334
• 20 van der Ven J, Linz VC, Anic K. et al. A questionnaire-based survey on the diagnostic and therapeutic approaches for patients with STIC in Germany. Arch Gynecol Obstet 2023; 308: 527-534
• 21 Leitlinienprogramm Onkologie. S3-Leitlinie Diagnostik, Therapie und Nachsorge maligner Ovarialtumoren, Version 6.0 – Oktober 2024. AWMF-Registernummer: 032–035OL. 2024 Accessed December 23, 2024 at: https://www.leitlinienprogramm-onkologie.de/fileadmin/user_upload/Downloads/Leitlinien/Ovarialkarzinom/Version_6/LL_Ovarialkarzinom_Langversion_6.0.pdf
• 22 NCCN Guidelines: Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer, Version 3.2024. 15.07.2024 Accessed December 23, 2024 at: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1453
• 23 Ledermann JA, Matias-Guiu X, Amant F. et al. ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease. Ann Oncol 2024; 35: 248-266
• 24 Schneider S, Heikaus S, Harter P. et al. Serous Tubal Intraepithelial Carcinoma Associated With Extraovarian Metastases. Int J Gynecol Cancer 2017; 27: 444-451
• 25 Samimi G, Trabert B, Geczik AM. et al. Population Frequency of Serous Tubal Intraepithelial Carcinoma (STIC) in Clinical Practice Using SEE-Fim Protocol. JNCI Cancer Spectr 2018; 2: pky061
• 26 Statistisches Landesamt Rheinland-Pfalz. Auch 2023 trotz deutlich abgeschwächter Zuwanderung Bevölkerungszuwachs. Accessed September 24, 2024 at: https://www.statistik.rlp.de/themen/finanzen/news/nachrichtendetailseite/auch-2023-trotz-deutlich-abgeschwaechter-zuwanderung-bevoelkerungszuwachs
• 27 Statistisches Bundesamt. Bevölkerung nach Nationalität und Geschlecht 2024. Accessed October 02, 2024 at: https://www.destatis.de/DE/Themen/Gesellschaft-Umwelt/Bevoelkerung/Bevoelkerungsstand/Tabellen/liste-zensus-geschlecht-staatsangehoerigkeit.html%231346466
• 28 Runnebaum IB, Kather A, Vorwergk J. et al. Ovarian cancer prevention by opportunistic salpingectomy is a new de facto standard in Germany. J Cancer Res Clin Oncol 2023; 149: 6953-6966
• 29 Hanley GE, Pearce CL, Talhouk A. et al. Outcomes From Opportunistic Salpingectomy for Ovarian Cancer Prevention. JAMA Netw Open 2022; 5: e2147343
• 30 Tchartchian G, Bojahr B, Heils L. et al. Prophylactic Salpingectomy during Hysterectomy for Benign Disease: A Prospective Study to Evaluate High-Grade Serous Ovarian Carcinoma Precursors. J Clin Med 2022; 12: 296
• 31 Bonavina G, Busnelli A, Salmeri N. et al. Opportunistic salpingectomy at the time of vaginal hysterectomy: A systematic review and meta-analysis. Int J Gynaecol Obstet 2024; 166: 494-501
• 32 Harmsen MG, Piek JMJ, Bulten J. et al. Peritoneal carcinomatosis after risk-reducing surgery in BRCA1/2 mutation carriers. Cancer 2018; 124: 952-959
• 33 Labidi-Galy SI, Papp E, Hallberg D. et al. High grade serous ovarian carcinomas originate in the fallopian tube. Nat Commun 2017; 8: 1093
• 34 Lee YJ, Lee SW, Kim KR. et al. Pathologic findings at risk-reducing salpingo-oophorectomy (RRSO) in germline BRCA mutation carriers with breast cancer: significance of bilateral RRSO at the optimal age in germline BRCA mutation carriers. J Gynecol Oncol 2017; 28: e3
• 35 Matan LS, Perri T, Kogan L. et al. Ovarian cancer risk management in BRCA-mutation carriers: A comparison of six international and national guidelines. Eur J Obstet Gynecol Reprod Biol 2022; 278: 166-171
• 36 Kuchenbaecker KB, Hopper JL, Barnes DR. et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA 2017; 317: 2402-2416
• 37 Gootzen TA, Steenbeek MP, van Bommel M. et al. Risk-reducing salpingectomy with delayed oophorectomy to prevent ovarian cancer in women with an increased inherited risk: insights into an alternative strategy. Fam Cancer 2024;
• 38 Gaba F, Robbani S, Singh N. et al. Preventing Ovarian Cancer through early Excision of Tubes and late Ovarian Removal (PROTECTOR): protocol for a prospective non-randomised multi-center trial. Int J Gynecol Cancer 2021; 31: 286-291
• 39 Steenbeek MP, van Bommel MHD, intHout J. et al. TUBectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy in high-risk women to assess the safety of prevention: the TUBA-WISP II study protocol. Int J Gynecol Cancer 2023; 33: 982-987
• 40 Klinisch-epidemiologisches Krebsregister Brandenburg-Berlin. Unsere überregionale Zusammenarbeit. Accessed September 24, 2024 at: https://kkrbb.de/unsere-ueberregionale-zusammenarbeit/