Objective
We compared the outcomes of microinvasive squamous cell carcinoma and adenocarcinoma of the cervix and examined the safety of fertility-conserving treatment.
Study Design
The Surveillance, Epidemiology, and End Results database was used to identify all women with stage IA1 and IA2 cervical carcinoma diagnosed from 1988 to 2005. The treatment and outcomes of women with adenocarcinomas were compared with squamous cell carcinomas.
Results
A total of 3987 women including 988 with adenocarcinomas (24.8%) were identified. Women with adenocarcinoma were more often white and were younger ( P < .05 for all). Survival for stage IA1 adenocarcinomas (hazard ratio, 0.79; 95% confidence interval, 0.21–2.94) was similar to that of women with squamous cell tumors. For stage IA2 tumors, survival was similar for squamous cell and adenocarcinomas (hazard ratio, 0.51; 95% confidence interval, 0.18–1.47). For stage IA1 and IA2 adenocarcinomas, survival was similar for conization and hysterectomy.
Conclusion
Survival is similar for microinvasive adenocarcinomas and squamous cell carcinomas. Conization appears to be adequate treatment for microinvasive adenocarcinoma.
The incidence of invasive adenocarcinoma of the cervix is increasing. Population-based estimates now suggest that adenocarcinomas account for more than a quarter of all newly diagnosed cervical cancers in the United States. In certain racial and ethnic groups, adenocarcinomas have increased by nearly 50%. Whether the prognosis for adenocarcinomas differs from that of squamous cell carcinomas has long been debated.
Microinvasive carcinomas of the cervix are tumors with 5 mm or less of stromal invasion and 7.0 mm or less of lateral extension. These neoplasms are associated with an excellent prognosis, and many women with these tumors are candidates for conservative, uterine-preserving treatments.
Traditionally the classification of microinvasive cervical cancer has been limited to squamous cell carcinomas. In 2009, the International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer was revised so that microinvasive adenocarcinomas were staged using the same criteria as microinvasive squamous cell carcinomas.
Although the risk of parametrial spread and nodal metastasis in women with microinvasive adenocarcinomas appears to be low, radical hysterectomy is often considered the treatment of choice for these lesions. This aggressive treatment is in spite of the fact that a number of studies have suggested that survival for women with adenocarcinomas and less than 5 mm of cervical invasion is excellent. In addition to operative morbidity, radical hysterectomy results in loss of fertility that can be particularly problematic because many women with adenocarcinomas are young. To date, there have been few data directly comparing the outcomes of microinvasive adenocarcinomas and squamous cell carcinomas.
Given the uncertainty regarding the behavior of microinvasive adenocarcinoma of the cervix, we performed a population-based analysis to determine the natural history of microinvasive cervical adenocarcinoma. Specifically we compared the outcomes of women with microinvasive squamous cell carcinoma and adenocarcinoma and examined the safety of fertility-conserving treatment.
Materials and Methods
The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database was utilized. SEER is a population-based cancer registry that includes approximately 26% of the US population. SEER is composed of a number of geographically distinct tumor registries. The demographic characteristics of the SEER registries have been previously characterized and reported. Data from SEER 17 registries was utilized. The study received approval from the Columbia University Institutional Review Board.
Women with invasive adenocarcinomas and squamous cell carcinomas treated between 1988 and 2005 were selected. Patients with adenosquamous carcinomas were excluded. Clinical and pathologic data including age at diagnosis (≤40, 41-65, and >65 years of age), race (white, black, other), grade (1, 2, and 3), and marital status (married and single) were examined. Year of diagnosis was stratified as 1988-1993, 1994-2005, and 2000-2005 for analysis.
Patients were categorized based on the geographic area of residence within the United States at the time of diagnosis as: central (Detroit, Iowa, Kentucky, Louisiana, and Utah), eastern (Connecticut; New Jersey; Atlanta, GA; and rural Georgia), and western (Alaska; California; Hawaii; Los Angeles, CA; New Mexico; San Francisco, CA; San Jose, CA; and Seattle, WA).
Each patient’s primary treatment was classified as either conization or hysterectomy (extrafascial and radical). In addition, whether lymph node sampling was performed and the presence of nodal metastasis were recorded for each patient. The extent of disease codes were used to classify each patient’s stage based on the 2009 staging criteria of the FIGO. Patients with stage IA1 tumors had stromal invasion of 3 mm or less and 7 mm or less of lateral spread, whereas those with IA2 tumors had 3-5 mm of stromal invasion and 7 mm or less of lateral spread. The vital status of each patient was recorded.
Frequency distributions between categorical variables were compared using χ 2 tests. Cox proportional hazards models were developed to examine stage-specific survival. In the Cox proportional hazards analyses, we modeled the cancer-specific hazard ratios while controlling for other prognostic variables. The effect of histology on survival was also examined using Kaplan-Meier analysis and compared using the log-rank test. All analyses were performed with SAS version 9.2 (SAS Institute Inc, Cary, NC).
Results
A total of 3987 women including 988 with adenocarcinomas (24.8%) and 2999 with squamous cell carcinomas with microinvasive disease (75.2%) were identified. The demographic and clinical variables of the cohort are displayed in Table 1 . Stage IA1 tumors were noted in 554 of the women with adenocarcinomas (56.1%) and in 1610 of those with squamous neoplasms (53.7%), whereas 43.9% of women with adenocarcinomas and 46.3% of those with squamous cell carcinomas had stage IA2 tumors ( P = .19). Women with adenocarcinoma were more often white (85.6% vs 78.1%), were younger at diagnosis, and were more likely to be married ( P < .05 for all). Conization was the primary treatment in 26.1% of women with squamous cell carcinomas and in 18.4% of patients with adenocarcinomas ( P < .0001).
| Characteristic | Squamous cell (n = 2999) | Adenocarcinoma (n = 988) | P value | ||
|---|---|---|---|---|---|
| n | % | n | % | ||
| Age at diagnosis, y | .05 | ||||
| ≤40 | 1428 | (47.6) | 493 | (49.9) | |
| 41-65 | 1319 | (44.0) | 435 | (44.0) | |
| >65 | 252 | (8.4) | 60 | (6.1) | |
| Race | < .0001 | ||||
| White | 2341 | (78.1) | 846 | (85.6) | |
| Black | 359 | (12.0) | 43 | (4.4) | |
| Other | 299 | (10.0) | 99 | (10.0) | |
| Year of diagnosis | .41 | ||||
| 1988-1993 | 487 | (16.2) | 146 | (14.8) | |
| 1994-1999 | 869 | (29.0) | 279 | (28.2) | |
| 2000-2005 | 1643 | (54.8) | 563 | (57.0) | |
| SEER registry | .05 | ||||
| West | 1502 | (50.1) | 539 | (54.6) | |
| Central | 759 | (25.3) | 229 | (23.2) | |
| East | 738 | (24.6) | 220 | (22.3) | |
| Marital status | < .0001 | ||||
| Married | 1466 | (48.9) | 613 | (62.0) | |
| Single | 1347 | (44.9) | 341 | (34.5) | |
| Unknown | 186 | (6.2) | 34 | (3.4) | |
| Tumor grade | < .0001 | ||||
| 1 | 266 | (8.9) | 297 | (30.1) | |
| 2 | 545 | (18.2) | 216 | (21.9) | |
| 3 | 285 | (9.5) | 65 | (6.6) | |
| Unknown | 1903 | (63.5) | 410 | (41.5) | |
| Stage | .19 | ||||
| IA1 | 1610 | (53.7) | 554 | (56.1) | |
| IA2 | 1389 | (46.3) | 434 | (43.9) | |
| Treatment | < .0001 | ||||
| Conization | 784 | (26.1) | 182 | (18.4) | |
| Hysterectomy | 2215 | (73.9) | 806 | (81.6) | |
| Lymphadenectomy | < .0001 | ||||
| Yes | 913 | (30.4) | 535 | (54.2) | |
| No | 2086 | (69.6) | 453 | (45.9) | |
| Radiation | 1.00 | ||||
| Yes | 176 | (5.9) | 58 | (5.9) | |
| No | 2823 | (94.1) | 930 | (94.1) | |
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