Small cell neuroendocrine carcinoma of the cervix: analysis of the prognosis and role of radiation therapy for 43 cases

Objective: To explore the outcomes and pattern of recurrence in patients with small cell neuroendocrine carcinoma of the cervix (SCNEC), and to determine the effects of adjuvant radiation therapy on survival in patients with early-stage disease. Methods: A retrospective analysis of 43 patients with SCNEC was carried out at Zhejiang Provincial Tumor Hospital between January 1985 and August 2007. All pathological specimens were examined and definitively diagnosed by two independent pathologists. The radiotherapeutic efficacy and prognosis of SCNEC were explored. Patient survival status was analyzed with the Kaplan-Meier method and survival rate was compared with the log-rank test; p < 0.05 was considered statistically significant. Results: Of 43 patients, 32 were early-stage and 11 were advance-stage. The median age was 45 years (range 25-85 years). There were 21 cases of metastasis or progression occurring in the lungs, retroperitoneal lymph node and brain within two years. In early-stage patients, distant metastasis or progression occurred in 13 cases within two years. The estimated 5-year survival rate for the entire group was 29%. Median overall survival for patients with early-stage disease was 89.6 months and 34.4 months for patients with advance-stage disease (p = 0.001). The 3-year survival for early-stage patients who received postoperative adjuvant chemotherapy was 57.1% compared with 56.4% for those who underwent adjuvant chemoradiotherapy, and their median survival periods were 84.7 and 89.1 months, respectively (p = 0.671). Conclusion: We confirmed the unfavorable prognosis related to early nodal and hematogenous metastasis in SCNEC, resulting in a relatively poor prognosis; clinical staging was an important prognostic factor. Chemoradiotherapy may be provided for advance-stage patients. For early-stage patients, the efficacy and site of postoperative adjuvant radiotherapy need further evaluation.

Small cell carcinoma; Neuroendocrine; Uterine cervix; Prognosis treatment outcome radiation

[1] Chung H.H., Jang M.J., Jung K.W., Won Y.J., Shin H.R., Kim J.W., Lee H.P.: “Cervical cancer incidence and survival in Korea: 1993-2002”. Int. J. Gynecol. Cancer, 2006, 16, 1833.

[2] Crowder S., Tuller E.: “Small cell carcinoma of th female genital tract”. Semin. Oncol., 2007, 34, 57.

[3] Tsunoda S., Jobo T., Arai M., Imai M., Kanai T., Tamura T. et al.: “Small cell carcinoma of the uterine cervix: a clinicopathologic study of 11 cases”. Int. J. Gynecol. Cancer, 2005, 15, 295.

[4] McCusker M.E., Coté T.R., Clegg L.X., Tavassoli F.J.: “Endocrine tumors of the uterine cervix: incidence, demographics, and survival with comparison to squamous cell carcinoma”. Gynecol. Oncol., 2003, 88, 333.

[5] Viswanathan A.N., Deavers M.T., Jhingran A., Ramirez P.T., Levenback C., Patricial J., Eifel P.: “Small cell neuroendocrine carcinoma of the cervix: outcome and patterns of recurrence”. J. Gynecol. Oncol., 2004, 93, 27.

[6] Chan J.K., Loizzi V., Burger R.A., Rutgers J., Monk B.J.: “Prognostic factors in neuroendocrine small cell cervical carcinoma: a multivariate analysis”. J. Cancer, 2003, 97, 568.

[7] Boruta II D.M., Schorge J.O., Duska L.A., Crum C.P., Castrillon D.H., Sheets E.E. et al.: “Multimodality therapy in early-stage neuroendocrine carcinoma of the uterine cervix”. Gynecol. Oncol., 2001, 81, 82.

[8] Zivanovic O., Leitao M.M., Park K.J., Zhao H., Diaz J.P., Konner J. et al.: “Small cell neuroendocrine carcinoma of the cervix: Analysis of outcome, recurrence pattern and the impact of platinum-based combination chemotherapy”. Gynecol. Oncol., 2009, 112, 590.

[9] Lee J.M., Lee K.B., Nam J.H., Ryu S.Y., Bae D.S., Park J.T. et al.: “Prognostic factors in FIGO Stage IB-IIA small cell neuroendocrine carcinoma of the uterine cervix treated surgically: results of a multi-center retrospective Korean study”. Ann. Oncol., 2008, 19, 321.

[10] Cohen J., Kapp D.S., Shin J.Y., Urban R., Sherman A.E., Chen L.M. et al.: “Small cell carcinoma of the cervix: treatment and survival outcomes of 188 patients”. Am. J. Obstet. Gynecol., 2010, 203, 347e1.

[11] Yang D.H., Kim J.K., Kim K.W., Bae S.J.: “MRI of small cell Carcinoma of the uterine cervix with pathologic correlation”. J. AJR, 2004, 182, 1255.

[12] Hoskins P.J., Swenerton K.D., Pike J.A., Lim P., Parsons C.A., Wong F., Lee N.: “Small-cell carcinoma of the cervix: fourteen years of experience at a single institution using a combinedmodality regimen of involved-field irradiation and platinum-based combination chemotherapy”. J. Clin. Oncol., 2003, 21, 3495.

[13] Lee S.W., Nam J.H., Kim D.Y., Kim J.H., Kim K.R., Kim Y.M., Kim Y.T.: “Unfavorable prognosis of small cell neuroendocrine carcinoma of the uterine cervix: a retrospective matched casecontrol study”. Int. J. Gynecol. Cancer, 2010, 20, 411.

[14] Kasamatsu T., Sasajima Y., Onda T., Sawada M., Kato T., Tanikawa M.: “Surgical treatment for neuroendocrine carcinoma of the uterine cervix”. Int. Fed. Gynecol. Obstet., 2007, 99, 225.

[15] Kapp D.S., Cohen J., Shin J.Y., Urban R., Sherman A.E., Chen L.M. et al.: “The prognostic factors responsible for survival of women with neuroendocrine small-cell cervical carcinoma-A study of 188 women”. J. Am. Soc. Clin. Oncol., 2007, 25 (18S), 5539.

[16] Huang C.Y., Chen Y.L., Chu T.C., Cheng W.F., Hsieh C.Y., Lin M.C.: “Prognostic factors in women with early-stage small cell carcinoma of the uterine cervix”. Oncol. Res., 2009, 18, 279.

[17] Bermu´dez A., Vighi S., Garcı´a A.: “Neuroendocrine cervical carcinoma: a diagnostic and therapeutic challenge”. Gynecol. Oncol., 2001, 82, 32.

[18] Sevin B.U., Method M.W., Nadji M., Lu Y., Averette H.A.: “Efficacy of radical hysterectomy as treatment for patients with small cell carcinoma of the cervix”. J. Cancer, 1996, 77, 1489.

[19] Pijls-Johannesma M., Ruysscher De, Vansteenkiste J., Kester A., Rutten I., Lambin P: “Timing of chest radiotherapy in patients with limited stage small cell lung cancer: a systematic review and meta-analysis of randomised controlled trials”. Cancer Treat. Rev., 2007, 33, 461.

[20] van Loon J., Offermann C., Bosmans G., Wanders R., Dekker A., Borger J.: “18FDG-PET based radiation planning of mediastinal lymph nodes in limited disease small cell lung cancer changes radiotherapy fields: a planning study”. Radiother. Oncol., 2008, 87, 49.

[21] Simon G.R., Turrisi A.: “Management of small cell lung cancer:ACCP evidence-based clinical practice guidelines (2nd edition)”. Chest, 2007, 132, 324S.

[22] Vines E.F., Le Pechoux C., Arriagada R.: “Prophylactic cranial irradiation for patients with small cell lung cancer in complete remission”. N. Engl. J. Med., 2003, 341, 476.

[23] Slotman B., Faivre-Finn C., Kramer G., Rankin E., Snee M., Hatton M. et al.: “Prophylactic cranial irradiation in extensive small cell lung cancer”. N. Engl. J. Med., 2007, 357, 664.

[24] Brennan S.M., Gregory D.L., Stillie A., Herschtal A., Manus M.M., Ball D.L.: “Should extrapulmonary small cell cancer be managed like small cell lung cancer”. Cancer, 2010, 116, 888.

[25] Chen J., Macdonald O.K., Gaffney D.K.: “Incidence, mortality, and prognostic factors of small cell carcinoma of the cervix”. Obstet. Gynecol., 2008, 111, 1394.

[26] Weed J.C. Jr., Graff A.T., Shoup B., Tawfik O.: “Small cell undifferentitiated (neuroendocrine) carcinoma of the uterine cervix”. J. Am. Coll. Surg., 2003, 197, 44.