Prognostic factors for and pattern of lymph-node involvement in patients with operable cervical cancer
- 11 Downloads
Lymph node metastases significantly worsen the prognosis in cervical carcinoma. Risk factors—pathological and patient related—could select patients at high risk for lymph node involvement.
This retrospective analysis was performed by analyzing data from patients with cervical carcinoma treated between 2000 and 2017 at the Department of Obstetrics and Gynecology of the University Hospital Ulm.
In total, 261 patients with cervical carcinoma (International Federation of Gynecology and Obstetrics (FIGO) stage IA–IIB) and lymphadenectomy with at least 10 removed lymph nodes were available for analysis. Overall, 86 (33.0%) patients had lymph node metastases; 73 patients had pelvic lymph node metastases only and 13 patients had both pelvic and paraaortic lymph node metastases. Lymph node metastases were found most often in the region of the external iliac artery and obturator fossa, with 57.0% and 54.7% of all 86 node-positive patients, respectively. Univariable analyses showed that presence of lymph node metastases was significantly associated with both preoperative FIGO stage (p = 0.001) and final pathological tumor stage (p < 0.001), status of resection margin (p = 0.002), lymphovascular space invasion (LVSI), (p < 0.001) and vascular space invasion, (p < 0.001). In a multivariable logistic regression model with presence of lymph node metastases (yes/no) as binary response variable, only LVSI (p < 0.001) and body mass index (BMI), (p = 0.035) remained as significant independent predictors of lymph node involvement. Subgroup analyses showed that LVSI was a significant predictive factor for lymph node involvement in patients with a preoperatively assessed FIGO stage < IIB (p < 0.001), but not for patients with a preoperatively assessed FIGO stage ≥ IIB (p = 0.122).
The risk factor LVSI should play an important role in deciding whether an individualized therapy concept is based on escalating or deescalating treatment. In future, the sentinel concept could reduce morbidity and at the same time provide an important prognostic assessment for a subset of cervical cancer patients.
KeywordsCervical cancer Lymph node Prognostic factor Pattern LVSI
PW: Protocol/project development, Data collection or management, Data analysis, Manuscript writing/editing. WJ: Protocol/project development, Manuscript editing. CS: Manuscript editing, Protocol development. ADG: Data collection, Manuscript editing. NDG: Data collection, Manuscript editing. TWPF: Data analysis, Statistics, Manuscript editing.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This retrospective analysis was approved by the ethic committee of the university of Ulm, Germany. Number 133/16.
Informed consent was not possible in this study due to retrospective data collection.
- 2.Takekuma M, Kasamatsu Y, Kado N, Kuji S, Tanaka A, Takahashi N, Abe M, Hirashima Y (2017) The issues regarding postoperative adjuvant therapy and prognostic risk factors for patients with stage I–II cervical cancer: a review. J Obstet Gynaecol Res 43:617–626. https://doi.org/10.1111/jog.13282 CrossRefPubMedGoogle Scholar
- 3.Bhatla N, Berek JS, Cuello Fredes M, Denny LA, Grenman S, Karunaratne K, Kehoe ST, Konishi I, Olawaiye AB, Prat J, Sankaranarayanan R, Brierley J, Mutch D, Querleu D, Cibula D, Quinn M, Botha H, Sigurd L, Rice L, Ryu H-S, Ngan H, Mäenpää J, Andrijono A, Purwoto G, Maheshwari A, Bafna UD, Plante M, Natarajan J (2019) Revised FIGO staging for carcinoma of the cervix uteri. Int J Gynecol Obstet 145:129–135. https://doi.org/10.1002/ijgo.12749 CrossRefGoogle Scholar
- 4.Tsunoda AT, Marnitz S, Soares Nunes J, de Cunha Andrade CEM, Scapulatempo Neto C, Blohmer J-U, Herrmann J, Kerr LM, Martus P, Schneider A, Favero G, Köhler C (2017) Incidence of histologically proven pelvic and para-aortic lymph node metastases and rate of upstaging in patients with locally advanced cervical cancer: results of a prospective randomized trial. Oncology 92:213–220. https://doi.org/10.1159/000453666 CrossRefPubMedGoogle Scholar
- 5.Köhler C, Mustea A, Marnitz S, Schneider A, Chiantera V, Ulrich U, Scharf J-P, Martus P, Vieira MA, Tsunoda A (2015) Perioperative morbidity and rate of upstaging after laparoscopic staging for patients with locally advanced cervical cancer: results of a prospective randomized trial. Am J Obstet Gynecol 213:503.e1–503.e7. https://doi.org/10.1016/j.ajog.2015.05.026 CrossRefGoogle Scholar
- 6.Ferrandina G, Margariti PA, Smaniotto D, Petrillo M, Salerno MG, Fagotti A, Macchia G, Morganti AG, Cellini N, Scambia G (2010) Long-term analysis of clinical outcome and complications in locally advanced cervical cancer patients administered concomitant chemoradiation followed by radical surgery. Gynecol Oncol 119:404–410. https://doi.org/10.1016/j.ygyno.2010.08.004 CrossRefPubMedGoogle Scholar
- 7.Maggioni A, Benedetti Panici P, Dell’Anna T, Landoni F, Lissoni A, Pellegrino A, Rossi R, Chiari S, Campagnutta E, Greggi S, Angioli R, Manci N, Calcagno M, Scambia G, Fossati R, Floriani I, Torri V, Grassi R, Mangioni C (2006) Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis. Br J Cancer 95:699–704. https://doi.org/10.1038/sj.bjc.6603323 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Marth C, Landoni F, Mahner S, McCormack M, Gonzalez-Martin A, Colombo N (2017) ESMO Guidelines Committee, cervical cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol 28:iv72–iv83. https://doi.org/10.1093/annonc/mdx220 CrossRefGoogle Scholar
- 11.Rotman M, Sedlis A, Piedmonte MR, Bundy B, Lentz SS, Muderspach LI, Zaino RJ (2006) A phase III randomized trial of postoperative pelvic irradiation in stage IB cervical carcinoma with poor prognostic features: follow-up of a gynecologic oncology group study. Int J Radiat Oncol 65:169–176. https://doi.org/10.1016/j.ijrobp.2005.10.019 CrossRefGoogle Scholar
- 12.Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI, Zaino RJ (1999) A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: a Gynecologic Oncology Group Study. Gynecol Oncol 73:177–183. https://doi.org/10.1006/gyno.1999.5387 CrossRefPubMedGoogle Scholar
- 13.Morice P, Piovesan P, Rey A, Atallah D, Haie-Meder C, Pautier P, Sideris L, Pomel C, Duvillard P, Castaigne D (2003) Prognostic value of lymphovascular space invasion determined with hematoxylin-eosin staining in early stage cervical carcinoma: results of a multivariate analysis. Ann Oncol 14:1511–1517. https://doi.org/10.1093/annonc/mdg412 CrossRefPubMedGoogle Scholar
- 14.Monk BJ, Wang J, Im S, Stock RJ, Peters WA, Liu PY, Barrett RJ, Berek JS, Souhami L, Grigsby PW, Gordon W, Alberts DS (2005) Gynecologic oncology group, southwest oncology group, radiation therapy oncology group, rethinking the use of radiation and chemotherapy after radical hysterectomy: a clinical–pathologic analysis of a gynecologic oncology group/southwest oncology group/radiation therapy oncology group trial. Gynecol Oncol 96:721–728. https://doi.org/10.1016/j.ygyno.2004.11.007 CrossRefPubMedGoogle Scholar
- 15.Uno T, Ito H, Isobe K, Kaneyasu Y, Tanaka N, Mitsuhashi A, Suzuka K, Yamazawa K, Shigematsu N, Itami J (2005) Postoperative pelvic radiotherapy for cervical cancer patients with positive parametrial invasion. Gynecol Oncol 96:335–340. https://doi.org/10.1016/j.ygyno.2004.09.061 CrossRefPubMedGoogle Scholar
- 16.Höckel M, Horn L-C, Manthey N, Braumann U-D, Wolf U, Teichmann G, Frauenschläger K, Dornhöfer N, Einenkel J (2009) Resection of the embryologically defined uterovaginal (Müllerian) compartment and pelvic control in patients with cervical cancer: a prospective analysis. Lancet Oncol 10:683–692. https://doi.org/10.1016/S1470-2045(09)70100-7 CrossRefPubMedGoogle Scholar
- 18.Fleming ND, Frumovitz M, Schmeler KM, dos Reis R, Munsell MF, Eifel PJ, Soliman PT, Nick AM, Westin SN, Ramirez PT (2015) Significance of lymph node ratio in defining risk category in node-positive early stage cervical cancer. Gynecol Oncol 136:48–53. https://doi.org/10.1016/j.ygyno.2014.11.010 CrossRefPubMedGoogle Scholar
- 19.Chen Y, Zhang L, Tian J, Fu X, Ren X, Hao Q (2013) Significance of the absolute number and ratio of metastatic lymph nodes in predicting postoperative survival for the international federation of gynecology and obstetrics stage IA2 to IIA cervical cancer. Int J Gynecol Cancer 23:157–163. https://doi.org/10.1097/IGC.0b013e3182778bcf CrossRefPubMedGoogle Scholar
- 20.Kwon J, Eom K-Y, Kim YS, Park W, Chun M, Lee J, Kim YB, Yoon WS, Kim JH, Choi JH, Chang SK, Jeong BK, Lee SH, Cha J (2018) The prognostic impact of the number of metastatic lymph nodes and a new prognostic scoring system for recurrence in early-stage cervical cancer with high risk factors: a multicenter cohort study (KROG 15-04). Cancer Res Treat 50:964–974. https://doi.org/10.4143/crt.2017.346 CrossRefPubMedGoogle Scholar
- 22.Cibula D, Pötter R, Planchamp F, Avall-Lundqvist E, Fischerova D, Haie Meder C, Köhler C, Landoni F, Lax S, Lindegaard JC, Mahantshetty U, Mathevet P, McCluggage WG, McCormack M, Naik R, Nout R, Pignata S, Ponce J, Querleu D, Raspagliesi F, Rodolakis A, Tamussino K, Wimberger P, Raspollini MR (2018) 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. Int J Gynecol Cancer 28:641–655. https://doi.org/10.1097/igc.0000000000001216 CrossRefPubMedGoogle Scholar
- 26.Li X, Yin Y, Sheng X, Han X, Sun L, Lu C, Wang X (2015) Distribution pattern of lymph node metastases and its implication in individualized radiotherapeutic clinical target volume delineation of regional lymph nodes in patients with stage IA to IIA cervical cancer. Radiat Oncol 10:40. https://doi.org/10.1186/s13014-015-0352-5 CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Sakuragi N, Satoh C, Takeda N, Hareyama H, Takeda M, Yamamoto R, Fujimoto T, Oikawa M, Fujino T, Fujimoto S (1999) Incidence and distribution pattern of pelvic and paraaortic lymph node metastasis in patients with stages IB, IIA, and IIB cervical carcinoma treated with radical hysterectomy. Cancer 85:1547–1554CrossRefGoogle Scholar
- 28.Marnitz S, Köhler C, Bongardt S, Braig U, Hertel H, Schneider A (2006) German Association of Gynecologic Oncologists (AGO), topographic distribution of sentinel lymph nodes in patients with cervical cancer. Gynecol Oncol 103:35–44. https://doi.org/10.1016/j.ygyno.2006.01.061 CrossRefPubMedGoogle Scholar
- 31.Takeda N, Sakuragi N, Takeda M, Okamoto K, Kuwabara M, Negishi H, Oikawa M, Yamamoto R, Yamada H, Fujimoto S (2002) Multivariate analysis of histopathologic prognostic factors for invasive cervical cancer treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy. Acta Obstet Gynecol Scand 81:1144–1151CrossRefGoogle Scholar
- 34.Smith B, McCann GA, Phillips G, Backes FJ, O’Malley DM, Cohn DE, Fowler JM, Copeland LJ, Salani R (2017) Less radical surgery for early-stage cervical cancer: can conization specimens help identify patients at low risk for parametrial involvement? Gynecol Oncol 144:290–293. https://doi.org/10.1016/j.ygyno.2016.11.029 CrossRefPubMedGoogle Scholar
- 35.Bidus MA, Caffrey AS, You WB, Amezcua CA, Chernofsky MR, Barner R, Seidman J, Rose GS (2008) Cervical biopsy and excision procedure specimens lack sufficient predictive value for lymph-vascular space invasion seen at hysterectomy for cervical cancer. Am J Obstet Gynecol 199:151.e1–151.e4. https://doi.org/10.1016/j.ajog.2008.02.017 CrossRefGoogle Scholar