Small cell carcinoma of the cervix: treatment and survival outcomes of 188 patients

doi:10.1016/j.ajog.2010.04.019

American Journal of Obstetrics and Gynecology

Volume 203, Issue 4, October 2010, Pages 347.e1-347.e6

https://doi.org/10.1016/j.ajog.2010.04.019 Get rights and content

Objective

To determine the clinicopathologic factors associated with survival in neuroendocrine small cell cervical cancer patients.

Study Design

Patients were identified from a review of literature with an additional 52 patients from four hospitals. Kaplan-Meier and Cox regression methods were used for analyses.

Results

Of 188 patients, 135 had stages I-IIA, 45 stages IIB-IVA, and 8 stage IVB disease. A total of 55.3% underwent surgery, 16.0% had chemoradiation, 12.8% radiation, and 3.2% chemotherapy alone. The 5-year disease-specific survival in stage I-IIA, IIB-IVA, and IVB disease was 36.8%, 9.8%, and 0%, respectively (P < .001). Adjuvant chemotherapy or chemoradiation was associated with improved survival in patients with stages IIB-IVA disease compared with those who did not receive chemotherapy (17.8% vs 6.0%; P = .04). On multivariable analysis, early-stage disease and use of chemotherapy or chemoradiation were independent prognostic factors for improved survival.

Conclusion

Use of adjuvant chemotherapy or chemoradiation was associated with higher survival in small cell cervical cancer patients.

Section snippets

Materials and Methods

Fifty-two patients with neuroendocrine small cell cervical carcinoma who received diagnoses from 1979-2005 were identified from tumor registry databases at 4 hospitals (University of California-San Francisco, Stanford University, University of California-Irvine Medical Center, and Long Beach Memorial Medical Center). After institutional review board approval from these institutions, data were collected from hospital charts, office records, and tumor registry files. The remaining 136 patients

Results

Of 188 patients, 135 had stage I-IIA, 45 had IIB-IVA, and 8 had stage IVB disease.8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 The median age was 42 years (range, 20–87 years). Demographic characteristics of the patients are shown in Table 1. Vaginal bleeding at presentation was noted in 21.8% of patients and 8% had pain and pressure. Of 115 patients with tumor size documented, 80.0% had

Comment

Small cell cervical carcinoma is rare and is associated with a poor prognosis.⁴⁷ The Gynecologic Oncology Group attempted to study small cell cervical carcinoma in protocol 66 between 1982 and 1986, but failed to recruit sufficient numbers of patients. As a result, treatment decisions have been based on these small single institution studies, and have extrapolated treatment approaches from the management of small cell cancer of the lung. With 188 patients in this report, to our knowledge, this

References (52)

S. Tsunoda et al.
Small-cell carcinoma of the uterine cervix: a clinicopathologic study of 11 cases
Int J Gynecol Cancer
(2005)
H.H. Chung et al.
Cervical cancer incidence and survival in Korea: 1993-2002
Int J Gynecol Cancer
(2006)
S. Crowder et al.
Small cell carcinoma of the female genital tract
Semin Oncol
(2007)
M.E. McCusker et al.
Endocrine tumors of the uterine cervix: incidence, demographics, and survival with comparison to squamous cell carcinoma
Gynecol Oncol
(2003)
A.N. Viswanathan et al.
Small cell neuroendocrine carcinoma of the cervix: outcome and patterns of recurrence
Gynecol Oncol
(2004)
J. Albores-Saavedra et al.
Terminology of endocrine tumors of the uterine cervix: results of a workshop sponsored by the College of American Pathologists and the National Cancer Institute
Arch Pathol Lab Med
(1997)
J. Hintze
Number cruncher statistical systems
(2001)
D.J. Gersell
Small-cell undifferentiated carcinoma of the cervix: a clinicopathologic, ultrastructural, and immunocytochemical study of 15 cases
Am J Surg Pathol
(1988)
M. Morris et al.
Treatment of small cell carcinoma of the cervix with cisplatin, doxorubicin, and etoposide
Gynecol Oncol
(1992)
B.U. Sevin et al.
Efficacy of radical hysterectomy as treatment for patients with small cell carcinoma of the cervix
Cancer
(1996)

A.N. Walker et al.

Cervical neuroendocrine carcinoma: a clinical and light microscopic study of 14 cases

Int J Gynecol Pathol

(1988)

G. Ueda et al.

Neuroendocrine carcinoma of the uterus

Curr Top Pathol

(1992)

R. Pazdur et al.

Neuroendocrine carcinoma of the cervix: implications for staging and therapy

Gynecol Oncol

(1981)

M.A. Lojek et al.

Cushing's syndrome with small cell carcinoma of the uterine cervix

Am J Med

(1980)

M.H. Louka et al.

Carcinoid tumors of the uterine cervix: response to combination chemotherapy and radiotherapy

Am J Clin Oncol

(1982)

M. Yamasaki et al.

Argyrophil small cell carcinomas of the uterine cervix

Int J Gynecol Pathol

(1984)

P. Groben et al.

The pathologic spectrum of small cell carcinoma of the cervix

Int J Gynecol Pathol

(1985)

W.A. Turner et al.

Neuroendocrine carcinoma of the uterine cervix complicated by pregnancy: case report and review of the literature

Obstet Gynecol

(1986)

R.J. Barrett et al.

Neuroendocrine features in poorly differentiated and undifferentiated carcinomas of the cervix

Cancer

(1987)

R. Kodousek et al.

[Malignant apudoma (argyrophilie carcinoma) of the uterine cervix in a 24-year-old woman in pregnancy]

Cesk Patol

(1976)

N. Tsukamoto et al.

Carcinoma of the uterine cervix with variegated histological patterns and calcitonin production

Gynecol Oncol

(1989)

E.E. Sheets et al.

Surgically treated, early-stage neuroendocrine small-cell cervical carcinoma

Obstet Gynecol

(1988)

O. Abulafia et al.

Adjuvant chemotherapy in stage IB neuroendocrine small cell carcinoma of the cervix

Acta Obstet Gynecol Scand

(1995)

P.J. Hoskins et al.

Small-cell carcinoma of the cervix: fourteen years of experience at a single institution using a combined-modality regimen of involved-field irradiation and platinum-based combination chemotherapy

J Clin Oncol

(2003)

A.J. Jacobs et al.

Oat cell carcinoma of the uterine cervix in a pregnant woman treated with cis-diamminedichloroplatinum

Gynecol Oncol

(1980)

G.S. Lewandowski et al.

A potential role for intensive chemotherapy in the treatment of small cell neuroendocrine tumors of the cervix

Gynecol Oncol

(1993)

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Clonal Origin and Lineage Ambiguity in Mixed Neuroendocrine Carcinoma of the Uterine Cervix
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Small-cell neuroendocrine carcinoma (SCNEC) of the cervix is a rare disease characterized by a high incidence of mixed tumors with other types of cancer. The mechanism underlying this mixed phenotype is not well understood. This study established a panel of organoid lines from patients with SCNEC of the cervix and ultimately focused on one line, which retained a mixed tumor phenotype, both in vitro and in vivo. Histologically, both organoids and xenograft tumors showed distinct differentiation into either SCNEC or adenocarcinoma in some regions and ambiguous differentiation in others. Tracking single cells indicated the existence of cells with bipotential differentiation toward SCNEC and adenocarcinomas. Single-cell transcriptional analysis identified three distinct clusters: SCNEC-like, adenocarcinoma-like, and a cluster lacking specific differentiation markers. The expression of neuroendocrine markers was enriched in the SCNEC-like cluster but not exclusively. Human papillomavirus 18 E6 was enriched in the SCNEC-like cluster, which showed higher proliferation and lower levels of the p53 pathway. After treatment with anticancer drugs, the expression of adenocarcinoma markers increased, whereas that of SCNEC decreased. Using a reporter system for keratin 19 expression, changes in the differentiation of each cell were shown to be associated with the shift in differentiation induced by drug treatment. These data suggest that mixed SCNEC/cervical tumors have a clonal origin and are characterized by an ambiguous and flexible differentiation state.
Small cell neuroendocrine carcinoma of the cervix: From molecular basis to therapeutic advances
2023, Biomedical Journal
Small cell neuroendocrine carcinoma of the cervix (SCNECC) is an uncommon but aggressive uterine malignancy, the cause of which is generally associated with human papillomavirus (HPV) infection. A lack of clinical trials and evidence-based treatment guidelines poses therapeutic challenges to this rare tumor. At present, published data remain limited to case series and case reports. While clinical management has traditionally followed those of small cell neuroendocrine (SCNE) lung cancer relying on surgery, chemoradiation, and systemic chemotherapy, the prognosis remains dismal. Immune checkpoint inhibitors (ICIs), such as monoclonal antibodies that target programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1), atezolizumab and durvalumab have proven effective in extensive-stage SCNE lung cancer. Moreover, pembrolizumab has also proven beneficial effects when added onto chemotherapy in metastatic and recurrent HPV-associated non-SCNE cervical cancer. It holds promise to use ICIs in combination with chemoradiation to improve the clinical outcomes of patients with SCNECC. Future advances in our understanding of SCNECC biology – associated with the study of its genomic and molecular aberrations as well as knowledge from SCNE of lung and other extrapulmonary sites– would be helpful in discovering new molecular targets for drug development. Collaborative efforts and establishment of a SCNECC-specific biobank will be essential to achieve this goal.
The prognosis of patients with small cell carcinoma of the cervix: a retrospective study of the SEER database and a Chinese multicentre registry
2023, The Lancet Oncology
Small cell carcinoma of the cervix is a rare but poor prognosis pathological type of cervical cancer, for which advice in clinical guidelines is unspecific. We therefore aimed to investigate the factors and treatment methods that affect the prognosis of patients with small cell carcinoma of the cervix.
In this retrospective study, we collected data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries cohort and a Chinese multi-institutional registry. The SEER cohort included females diagnosed with small cell carcinoma of the cervix between Jan 1, 2000, and Dec 31, 2018, whereas the Chinese cohort included women diagnosed between Jun 1, 2006, and April 30, 2022. In both cohorts, eligibility was limited to female patients older than 20 years with a confirmed diagnosis of small cell carcinoma of the cervix. Participants who were lost to follow-up or those for whom small cell carcinoma of the cervix was not the primary malignant tumour were excluded from the multi-institutional registry, and those with an unknown surgery status (in addition to those for whom small cell carcinoma of the cervix was not the primary malignant tumour) were excluded from the SEER data. The primary outcome of this study was overall survival (length of time from the date of first diagnosis until the date of death from any cause, or the last follow-up). Kaplan-Meier analysis, propensity score matching, and Cox-regression analyses were used to assess treatment outcomes and risk factors.
1288 participants were included in the study; 610 in the SEER cohort and 678 in the Chinese cohort. Both univariable and multivariable Cox regression analysis (SEER hazard ratio [HR] 0·65 [95% CI 0·48–0·88], p=0·0058; China HR 0·53 [0·37–0·76], p=0·0005) showed that surgery was associated with a better prognosis. In subgroup analyses, surgery remained a protective factor for patients with locally advanced disease in both cohorts (SEER HR 0·61 [95% CI 0·39–0·94], p=0·024; China HR 0·59 [0·37–0·95]; p=0·029). Furthermore, the protective effect of surgery was observed among patients with locally advanced disease after propensity score matching in the SEER cohort (HR 0·52 [95% CI 0·32–0·84]; p=0·0077). In the China registry, surgery was associated with better outcomes in patients with stage IB3-IIA2 cancer (HR 0·17 [95% CI 0·05–0·50]; p=0·0015).
This study provides evidence that surgery improves outcomes of patients with small cell carcinoma of the cervix. Although guidelines recommend non-surgical methods as first-line treatment, patients with locally advanced disease or stage IB3-IIA2 cancer might benefit from surgery.
The National Key R&D Program of China and the National Natural Science Foundation of China.
The role of postoperative radiation after radical hysterectomy for women with early-stage neuroendocrine carcinoma of the cervix: A meta-analysis
2023, Gynecologic Oncology
Neuroendocrine carcinoma of the cervix (NECC) is an aggressive disease with high rates of nodal disease spread even in seemingly cervix-confined disease. Many providers routinely prescribe postoperative radiation therapy in an effort to reduce recurrences despite a lack of supporting studies. The objective of this study was to determine recurrence and mortality in patients with early-stage NECC who had pelvic radiation after radical hysterectomy compared to those who did not receive radiation.
We performed a meta-analysis of 13 unique studies that reported recurrence and/or mortality for patients with early-stage NECC who underwent radical hysterectomy with or without adjuvant radiation therapy.
In 5 studies that reported overall recurrence rates, 63 (52.5%) of 120 patients who received postoperative radiation recurred compared to 70 (37.8%) of 185 patients who did not (RR 1.21, 95% CI: 0.85–1.70, p = 0.29). In 5 studies that reported pelvic recurrence rates, there were 15 pelvic recurrences (12.5%) in the 120 patients who received postoperative radiation compared to 45 pelvic recurrences (24.3%) in the 185 patients who did not (RR 0.60, 95% CI: 0.34–1.08, p = 0.09). In 13 studies that reported mortality rate, there were 138 deaths (34.8%) in 396 patients who received postoperative radiation therapy compared to 223 (35.2%) in 632 patients who did not (RR 1.08, 95% CI: 0.75–1.56, p = 0.66).
The addition of routine postoperative radiation therapy in all patients with early-stage NECC after radical hysterectomy may reduce pelvic recurrences but does not appear to decrease overall recurrence or death. However, there may still be a role for postoperative radiation therapy in patients with additional high-risk pathologic factors.
High grade neuroendocrine carcinoma of the cervix
2023, Diagnosis and Treatment of Rare Gynecologic Cancers
High grade neuroendocrine carcinoma (NEC) of the cervix consists of small cell, large cell, and undifferentiated NEC. This subtype accounts for only 1%–2% of all cervical cancer cases. Unlike in patients with the more common subtypes of squamous cell and adenocarcinoma, women with high grade NEC have a higher risk of metastatic disease at diagnosis, higher recurrence rates, and decreased survivals. Treatments for newly diagnosed disease often consist of surgery, radiation, and/or chemotherapy. Treatment for recurrence is exceedingly limited with few active agents.
Small cell neuroendocrine carcinoma of the cervix: Analysis of prognostic factors and patterns of metastasis
2022, Gynecologic Oncology Reports
To describe characteristics and outcomes of patients with small cell neuroendocrine carcinoma of the cervix (SCNCC) and determine the staging system most predictive of outcome—the two-tier (limited-stage [LS] vs. extensive-stage [ES]) or International Federation of Gynecology and Obstetrics (FIGO) staging system.
Patients with SCNCC evaluated at our institution from 1/1/1990–6/30/2021 were included. Medical records were reviewed for variables of interest. Appropriate statistical tests were performed to determine associations. Survival curves were created using the Kaplan-Meier method. Concordance probability estimates (CPEs) were calculated to evaluate the prediction probability of the staging systems.
Of 63 patients, 41 had LS and 22 ES SCNCC. Patients with ES disease were significantly older than those with LS disease (median, 54 and 37 years, respectively; p < 0.001). Smoking status, race, and history of HPV were not associated with stage or outcomes. Forty-eight patients had metastatic disease (24 [50%] at initial diagnosis). The most common first sites of metastasis were lung (n = 20/48, 42%), lymph nodes (n = 19/48, 40%), and liver (n = 13/48, 27%). Nine patients had brain metastasis (8 symptomatic at recurrence; 1 asymptomatic at initial diagnosis). Both staging systems were associated with progression-free and overall survival. Adjusted CPE found the FIGO staging system was more predictive of outcomes than the two-tier staging system.
Providers should have a low threshold to obtain brain imaging for patients with SCNCC, especially in the presence of visceral metastases. FIGO staging should be used to classify SCNCC. Further research is necessary to understand prognostic factors of this rare disease.

View all citing articles on Scopus

: Cite this article as: Cohen JG, Kapp DS, Shin JY, et al. Small cell carcinoma of the cervix: treatment and survival outcomes of 188 patients. Am J Obstet Gynecol 2010;203:347.e1-6.

: Reprints not available from the authors.

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ResearchOncologySmall cell carcinoma of the cervix: treatment and survival outcomes of 188 patients

Objective

Study Design

Results

Conclusion

Section snippets

Materials and Methods

Results

Comment

Small-cell carcinoma of the uterine cervix: a clinicopathologic study of 11 cases

Int J Gynecol Cancer

Cervical cancer incidence and survival in Korea: 1993-2002

Int J Gynecol Cancer

Small cell carcinoma of the female genital tract

Semin Oncol

Endocrine tumors of the uterine cervix: incidence, demographics, and survival with comparison to squamous cell carcinoma

Gynecol Oncol

Small cell neuroendocrine carcinoma of the cervix: outcome and patterns of recurrence

Gynecol Oncol

Terminology of endocrine tumors of the uterine cervix: results of a workshop sponsored by the College of American Pathologists and the National Cancer Institute

Arch Pathol Lab Med

Number cruncher statistical systems

Small-cell undifferentiated carcinoma of the cervix: a clinicopathologic, ultrastructural, and immunocytochemical study of 15 cases

Am J Surg Pathol

Treatment of small cell carcinoma of the cervix with cisplatin, doxorubicin, and etoposide

Gynecol Oncol

Efficacy of radical hysterectomy as treatment for patients with small cell carcinoma of the cervix

Cancer

Cervical neuroendocrine carcinoma: a clinical and light microscopic study of 14 cases

Int J Gynecol Pathol

Neuroendocrine carcinoma of the uterus

Curr Top Pathol

Neuroendocrine carcinoma of the cervix: implications for staging and therapy

Gynecol Oncol

Cushing's syndrome with small cell carcinoma of the uterine cervix

Am J Med

Carcinoid tumors of the uterine cervix: response to combination chemotherapy and radiotherapy

Am J Clin Oncol

Argyrophil small cell carcinomas of the uterine cervix

Int J Gynecol Pathol

The pathologic spectrum of small cell carcinoma of the cervix

Int J Gynecol Pathol

Neuroendocrine carcinoma of the uterine cervix complicated by pregnancy: case report and review of the literature

Obstet Gynecol

Neuroendocrine features in poorly differentiated and undifferentiated carcinomas of the cervix

Cancer

[Malignant apudoma (argyrophilie carcinoma) of the uterine cervix in a 24-year-old woman in pregnancy]

Cesk Patol

Carcinoma of the uterine cervix with variegated histological patterns and calcitonin production

Gynecol Oncol

Surgically treated, early-stage neuroendocrine small-cell cervical carcinoma

Obstet Gynecol

Adjuvant chemotherapy in stage IB neuroendocrine small cell carcinoma of the cervix

Acta Obstet Gynecol Scand

Small-cell carcinoma of the cervix: fourteen years of experience at a single institution using a combined-modality regimen of involved-field irradiation and platinum-based combination chemotherapy

J Clin Oncol

Oat cell carcinoma of the uterine cervix in a pregnant woman treated with cis-diamminedichloroplatinum

Gynecol Oncol

A potential role for intensive chemotherapy in the treatment of small cell neuroendocrine tumors of the cervix

Gynecol Oncol

Research
Oncology
Small cell carcinoma of the cervix: treatment and survival outcomes of 188 patients