Trends in the use of radiation and chemotherapy in the initial management of patients with carcinoma of the uterine cervix.

PURPOSE: The Commission on Cancer of the American College of Surgeons conducts Patient Care Evaluation studies to describe practice patterns and trends in disease management. This report surveys changing strategies in the initial treatment of patients with invasive cancer of the uterine cervix. METHODS AND MATERIALS: Using a standard data collection form designed by a multidisciplinary committee of specialists, cancer registrars at 703 hospitals submitted anonymous data on 11,721 total cervical cancer patients diagnosed in 1984 and 1990. RESULTS: Between the two study years, the use of radiation as all, or a component, of the initial course of therapy declined from 70 to 60.3%, coincident with a 32.3% increase in the use of hysterectomy alone and a 33.7% reduction in the use of radiation alone. The percentage of all patients receiving combined hysterectomy and radiation (preoperative or postoperative) remained virtually unchanged--10.2% in 1984, and 9.3% in 1990. However, women who were treated by hysterectomy in 1990 were less likely to receive radiation as part of their treatment than patients treated by hysterectomy in 1984. Among patients treated by radiation without hysterectomy, the use of intracavitary brachytherapy techniques substantially exceeded interstitial brachytherapy techniques in both study years. Among patients treated by local radiation without hysterectomy, the frequency of adjunctive chemotherapy use increased from 6.9% in 1984 to 24.8% in 1990, with chemotherapy and radiation increasingly administered concurrently rather than sequentially. Although differences based on age, histology, race/ethnicity, and insurance status were observed, these general management trends were seen in all groups. CONCLUSIONS: Changes in the utilization of radiation and surgery may reflect the increasing surgical involvement of gynecologic oncologists in the management of early stage cervical cancer, rather than significant alterations in the demographics of the disease. Although brachytherapy is recognized as an important component of radiation treatment, some patients may not receive the potential benefit of this modality. Despite controversy concerning its efficacy, the use of adjuvant systemic chemotherapy to supplement local treatment modalities appears to be increasing rapidly.

The National Cancer Data Base report on endometrial carcinoma in African-American women.

BACKGROUND: Although the incidence of uterine carcinoma is lower among African-American women compared with white women, the mortality rates are higher for African-American patients. This report is part of an ongoing series on gynecologic malignancies in African-American women. METHODS: Hospital registry reports collected by the National Cancer Data Base were used to describe some of the differences in case presentation and management characteristics of endometrial carcinoma in these two groups. The cases represented 52,307 Non-Hispanic white and 3226 African-American women diagnosed with primary carcinoma of the endometrium between 1988-1994. RESULTS: More African-American patients were diagnosed with less favorable histologies than white patients, at more advanced stages of disease, and with less tumor differentiation. Income had no effect on stage or grade. African-American patients were treated less often for their tumor at every stage of diagnosis compared with white women. Income generally had no effect on whether treatment was provided, but limited income was associated with a lack of treatment in African-American patients with American Joint Committee on Cancer Stage IV tumors. African-American women were less frequently treated surgically and, among surgically treated patients at advanced stages of disease, they received adjuvant radiotherapy less often and chemotherapy more often than white patients. Five-year survival was poorer for African-American women, even for patients with the more favorable Stage I adenocarcinoma who were treated surgically. CONCLUSIONS: All patients, regardless of race, should be treated appropriately as dictated by medical and prognostic factors and not by race. Although no screening methods currently exist for endometrial carcinoma, the development of procedures for identifying patients at risk for the prognostic factors that lead to a poor outcome should be a primary focus.

The National Cancer Data Base report on malignant epithelial ovarian carcinoma in African-American women.

BACKGROUND: Epithelial ovarian carcinoma is the fifth most common cause of cancer death among African-American women. Although the incidence rate of ovarian carcinoma for whites is higher than that for African Americans, the relative survival rate for African Americans is poorer. METHODS: Data were cases submitted to the National Cancer Data Base for invasive epithelial tumors of the ovary diagnosed between 1985-1988 and 1990-1993. African-American women with epithelial ovarian carcinoma were compared with non-Hispanic white women with the same disease. The groups of white women with which African-American women were compared were classified as "White-same facility" and "White-other facility." "White-same facility" were white patients from hospitals that contributed a substantial proportion of African-American patients. "White-other facility" were white patients from hospitals that contributed few or no African-American patients. No patient had a history of prior cancer. RESULTS: African-American women with advanced invasive epithelial ovarian carcinoma were less often treated with combined surgery and chemotherapy and more often treated with chemotherapy only. African-American women were twice as likely as white women not to receive appropriate treatment. African-American women had poorer survival rates than white women from the same or different hospitals, regardless of income. Among staged cases, African-American women were more often diagnosed with Stage IV disease than either group of white women. CONCLUSIONS: The current study findings show that African-American women with advanced epithelial ovarian carcinoma received less aggressive treatment than white women and had a poorer prognosis.

Diagnostic assessments in patients with invasive cancer of the cervix: a national patterns of care study of the American College of Surgeons.

Using a standard collection form designed by a multidisciplinary committee of specialists, cancer registrars at 703 hospitals submitted anonymous data on 11,721 patients with cervical cancer diagnosed during 2 study years, 1984 and 1990. Information concerning the initial use of diagnostic assessments was analyzed with respect to the potential influences of clinical stage, patient age, race/ethnicity, insurance status, and modalities of therapy employed. Estimates of the yield of diagnostic information for each test were correlated with clinical stage and patient age. Judged by the number of procedures performed, the intensity of pretreatment assessment declined between 1984 and 1990. Substantially increased use of the newer body imaging modalities (computerized axial tomography and magnetic resonance imaging) with high probabilities of revealing abnormalities attributed to cancer, balanced major declines in utilization of procedures historically important in staging and assessment (cystoscopy, proctoscopy, barium enema, excretory urography (intravenous pyelogram), bone scintography, and lymphangiography). Race/ethnicity and insurance status had no discernible independent impact on the intensity of diagnostic evaluation. Patients with more advanced clinical stages underwent more extensive testing, as did patients treated initially with radiation compared to surgery. Periodic review of assessment strategies would seem prudent to avoid widening discrepancies between sanctioned staging formalisms with endorsed and authorized appraisals and actual clinical practice.

Hysterectomy in invasive cervical cancer: a national patterns of care study of the American College of Surgeons.

BACKGROUND: As the use of Papanicolaou cytologic screening became widespread in the United States of America, there was a shift toward diagnosis of earlier clinical stages in patients with carcinoma of the cervix. This increase in early stage disease has also resulted in increased use of surgery as the primary treatment. Thus, it seems appropriate to investigate the role of hysterectomy in the modern treatment of patients with invasive carcinoma of the cervix, including survival rates and the role of the gynecologic oncologist. STUDY DESIGN: Approximately 1,800 hospitals were sent invitations to submit data on a standard collection form designed by a multidisciplinary committee of specialists. Cancer registrars at 703 hospitals submitted anonymous data on 11,721 patients with carcinoma of the cervix who were diagnosed or treated, or both, in 1984 and 1990. RESULTS: There were 6,570 (56.1 percent) women who had major operations. An operation with curative intent, either total hysterectomy (TAH) or radical type II or III hysterectomy with pelvic node dissection PND (RHPND), was carried out in 5,105 (43.6 percent) women, constituting 38.9 percent of the patients in 1984, and 48.2 percent of the patients in 1990. Overall (both years), 66.5 percent of patients had squamous cell carcinomas and 21.1 percent had adenocarcinomas. The type of operation performed was judged appropriate in 95.6 percent of the patients who underwent RHPND, but in only 80.0 percent of the patients who underwent TAH. Gynecologic oncologists performed 46.8 percent of the hysterectomies in 1984, and 63.8 percent in 1990. Recurrence and long-term survival data are available for the 1984 patients; five-year survival rates for women who underwent TAH (n = 1,013) and RHPND (n = 1,279) were 89 and 85 percent, respectively. A RHPND with negative nodes resulted in a 90 percent five-year survival rate (n = 916) as compared to 70 percent in those with positive nodes (n = 194). CONCLUSIONS: The use of hysterectomy as definitive therapy increased markedly from 1984 to 1990 and was associated with low complication and high five-year survival rates. Gynecologic oncologists now perform the majority of hysterectomies for this type of carcinoma, with general gynecologists playing a lesser role than in the earlier study year. Guidelines should be developed for the use of TAH in patients with invasive carcinoma of the cervix.

Treatment of cervical dysplasia with large loop excision of the transformation zone: is endocervical curettage necessary?

Endocervical curettage (ECC) is done during most colposcopic examinations. To evaluate the need for routine ECC, we reviewed the records of all new patients seen in the colposcopy clinic at our institution from July 15, 1992, to April 15, 1993. During the study period, ECC was done in 341 patients with an adequate colposcopy. Only one case of mild dysplasia was discovered after ECC in the 123 patients referred for evaluation of cervical intraepithelial neoplasia (CIN) I or atypia seen on Pap smear. ECC specimens were positive for dysplastic cells in only 3 of 203 patients (1.4%) in whom biopsy revealed CIN I or atypia, and Pap smears for all 3 patients were suggestive of more severe lesions. Routine ECC during the initial colposcopic examination adds expense and may cause significant patient discomfort. ECC can be safely omitted in patients with CIN I on referral Pap smear and before large loop excision of the transformation zone for treatment of more severe lesions.

Cervical carcinoma and pregnancy. A national patterns of care study of the American College of Surgeons.

BACKGROUND: The American College of Surgeons conducted a national patient care and evaluation study of invasive cervical carcinoma in pregnant patients. METHODS: Invasive cervical carcinoma was diagnosed in 161 patients who were pregnant at the time of diagnosis. A long term study of 78 patients diagnosed in 1984 was compared with a short term study of 83 patients diagnosed in 1990. RESULTS: The mean age of the patients was 31.8 years. Clinical stages were: IA (29%); IB (54%); IIA (6%); IIB (4%); IIIA (0%); IIIB (3%); IV (1%; AND IVB 3%). Thirty-one percent of patient were diagnosed in the first trimester, 34% in the second, and 35% in the third. A tumor size of 4 cm or larger in diameter was found in 36% of the patients diagnosed in the first trimester, 40% of the patients diagnosed in the second, and 38% of the patients diagnosed in the third. Patients were treated with surgery alone (86), radiotherapy alone (30), or with combination therapy (45). The overall 5-year survival rate for patients diagnosed in 1984 was 82%. In this group, the 5-year survival rate for patients diagnosed in the first trimester was 94.6%, in the second, 76.9%, and in the third, 68.9%. Comparing the two time periods, surgical therapy was performed more often by gynecologic oncologists in 1990 (69% vs. 42%), and a greater percentage of patients were diagnosed with a tumor size of 4 cm or larger in diameter (43% vs. 26%) as well as with stage IIB-IVB disease (15% vs. 6.7%). CONCLUSIONS: The prognosis of pregnant patients with invasive cervical carcinoma is similar to that for nonpregnant patients. The significant number of patients diagnosed in the second and third trimesters and the frequent finding of large tumors in all trimesters emphasize the need for patient education and early prenatal evaluation, including cervical cytology and biopsy of any clinically abnormal cervix.

The National Cancer Data Base report on endometrial cancer.

BACKGROUND: Previous Commission on Cancer data from the National Cancer Data Base (NCDB) have examined time trends in stage of disease, treatment patterns, and survival for selected cancers. The most current (1992) data for endometrial cancer are described here. METHODS: Four calls for data have yielded a total of 560,455 cancer cases diagnosed in 1986-1987, and 599,597 cancer cases diagnosed in 1992, from hospital cancer registries across the United States. RESULTS: Data were received for 36,341 endometrial cancer patients. No significant change in stage distribution for patients who were staged was noted with time, however, markedly fewer patients were reported with unknown stage in 1992 (15.6%) compared with 1986-1987 (45.1%). Blacks and low income groups were more likely to present with advanced stage disease. A 12.6% increase in patients undergoing nodal dissection as part of their surgical treatment occurred during this time period. More patients received surgery only as part of their treatment in 1992 (53.8%) vs. 42.6%). Advancing age, minority status, low income, and increasing grade all had a negative impact on survival. Blacks experienced a 25% reduction in survival compared to non-Hispanic Whites and Hispanics. CONCLUSIONS: Lack of improvement in detecting early disease indicates the lack of acceptable screening methodology for this disease. Blacks present with more advanced disease and subsequently have a decreased survival compared to non-Hispanic Whites. Time trends indicate that nodal dissection is becoming a more common surgical practice in this disease, and that radiation therapy is utilized less often. The current American Joint Committee on Cancer staging accurately reflects differences in prognosis by stage.

Squamous cell carcinoma of the uterine cervix. Patterns of thoracic metastases.

RATIONALE AND OBJECTIVES: Distant metastasis of cervical cancer, once considered rather uncommon, has become more common in recent years because of longer survival of the patients. The purpose of this study is to evaluate the radiographic patterns of its thoracic metastases correlating with the pathways of metastatic tumor spread. METHODS: The conventional radiographs (62 cases), thoracic computed tomography images (20 cases), and medical records of 62 patients with advanced squamous cell carcinoma of the uterine cervix with thoracic metastases who died of extensive disease and its complications during a recent 5-year period were reviewed retrospectively. RESULTS AND CONCLUSIONS: In addition to the most typical pattern of multiple pulmonary nodules (71%), mediastinal and hilar lymphadenopathy (32%) and pleural metastases (27%) were frequently observed. Rare findings included bone metastases (6%), endobronchial obstruction (5%), and lymphangitic carcinomatosis (3%). The mechanisms of metastasis in relation to the above manifestations are proposed.

Patterns of care for invasive cervical cancer. Results of a national survey of 1984 and 1990.

BACKGROUND: The American College of Surgeons conducted a national patient care and evaluation study of invasive cervical cancer to measure any changes in patterns of care for the years 1984 and 1990. METHODS: Hospitals with cancer programs were invited to submit data on up to 25 consecutive patients with newly diagnosed invasive cervical cancer for each of the two study years. Data were obtained from 684 hospitals on 5904 patients diagnosed in 1984 and from 700 hospitals on 5817 patients diagnosed in 1990. A long term study of patients diagnosed in 1984 was compared with a short term study of patients diagnosed in 1990. Survival data were described only for patients diagnosed in 1984. RESULTS: Of a total of 11,721 patients, 59.4% were diagnosed and treated at the reporting institution in 1984 and 54.8% in 1990. The remaining patients were referred for treatment after diagnosis elsewhere. The diagnosis was established by cervical biopsy for 69.8% of patients, by conization alone for 9.3%, and by both procedures for 11.8%. The histopathologic diagnoses were squamous cell carcinoma (79.8%), adenocarcinoma (15.8%), and other (4.4%). The stage distributions were as follows: IA, 15.9%; IB, 36.8%; IIA, 8.2%; IIB, 15.5%; IIIA, 2.5%; IIIB, 13.3%; IVA, 2.6%; and IVB, 5.2%. The stage was listed as unknown for 20.3% of patients. Patients were treated with surgery alone (29.2%), radiation alone (40.7%), chemotherapy alone (0.7%), or combination therapy (21.5%), and 7.9% received no treatment at the reporting institution. The overall survival for patients diagnosed in 1984 was 68.3%. Survival by stage in this group was as follows: IA, 93.7%; IB, 80.0%; IIA, 67.2%; IIB, 64.7%; III, 37.9%; and IV, 11.3%. CONCLUSIONS: These data indicate that invasive cervical cancer is highly curable when diagnosed early. During the 5-year period, stage distributions were similar, the use of extended hysterectomy increased, and gynecologic oncologists were more often the primary surgeons. The use of radiation alone decreased.

Is there really a difference in survival of women with squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma of the cervix?

BACKGROUND: The authors' aim was to assess whether there is a difference in biologic behavior and survival in comparing adenocarcinoma (AdCA), squamous cell carcinoma (SCC), and adenosquamous carcinoma (Ad/SC) of the cervix. METHODS: Cancer registrars at 703 hospitals submitted anonymous data on 11,157 patients with cervical cancer diagnosed and/or treated in 1984 and 1990 for a Patient Care Evaluation Study of the American College of Surgeons. Among these patients, 9351 (83.8%) had SCC; 1405 (12.6%), AdCA; and 401 (3.6%), Ad/SC cancers. There were no significant changes in percentages of the different histologic types between the study years 1984 and 1990, nor was the patient distribution different regarding age, race/ethnicity, and socioeconomic background for each histologic group. Furthermore, the distribution of patients who had had a hysterectomy did not change between 1984 and 1990. RESULTS: A larger percent of patients with SCC (63.8%) than those with Ad/SC (59.8%) or AdCA (50.2%) had tumors larger than 3 cm at greatest dimension. Early stage patients (IA, IB, IIA) often were treated by hysterectomy alone (45.5%) or combined with radiation (21.1%). The remaining patients (21.9%) received radiation alone. Of the patients with clinical stage I disease, 7.6% of Ad/CA patients, 15.5% of Ad/SC patients and 12.6% of SCC patients had positive nodes. Although patients with SCC had higher survival rates for all four clinical stages (I-IV), the differences were only significant for Stage II patients. Patients with clinical stage IB SCC and AdCA treated by surgery alone were found to have significantly better survival rates (93.1% and 94.6% at 5 years, respectively) than women treated by either radiation alone or a combination of surgery and radiation (P < 0.001, both histologic comparisons). For women with Ad/SC tumors, however, the 5-year survival rate was 87.3% for those receiving combined treatment compared with those receiving surgery alone (69.2%) or radiation alone (79.2%). However, these survival curves were not significantly different (P = 0.496). One hundred six patients with positive nodes were available for analysis. The 5-year survival rate of patients with SCC and positive nodes was 76.1%. Surprisingly, patients with Ad/SC and positive nodes had the highest 5-year survival rate (85.7%), whereas, women with AdCA and positive nodes had a sharply reduced 5-year survival rate (33.3%). The curves were significantly different (P < 0.01). For patients with clinical stage I, the risk factors for age, tumor size, nodal status, histologic features, and treatment were analyzed with Cox's multivariate regression. In this analysis, subset IB, greater tumor size, age 80 or older, and positive nodal status were each independently significant for poorer survival. Patients who were treated by surgery alone had a significantly better survival than patients who had other types of treatment or no treatment. Histologic characteristics had no significant effect on survival. In the analysis of patients with pathologic stage I disease, those with SCC had significantly poorer survival and those with Ad/SC had significantly better survival than patients with Ad/CA. Positive nodes had no significant independent effect on survival. In another analysis, tissue type was not found to be an important factor in recurrence time. CONCLUSIONS: 1. Ad/CA and Ad/SC tumors were found to represent 12.6% and 3.6%, respectively, of a large series (N = 11,157) of cervical cancers diagnosed in 1984 and 1990 and reported to the Commission on Cancer of the American College of Surgeons. 2. Two thirds of women with early clinical stage disease (IA, IB, IIA) had hysterectomy as all or part of their primary therapy. 3. No significant differences were found in 5-year survival among the three tissue types in any clinical stage except American Joint Committee on Cancer stage II.

T lymphocytes infiltrating advanced grades of cervical neoplasia. CD8-positive cells are recruited to invasion.

BACKGROUND: Impaired cellular immunity appears to be a risk factor for progression of cervical neoplasia, but the immunobiology of neoplastic progression is poorly understood. The objective of this study was to characterize the subpopulations of T lymphocytes that infiltrate various grades of cervical neoplasia including metaplasia to invasive cancer in immunocompetent women. METHOD: In 65 patients with a spectrum of cervical disease ranging from normal cytology to carcinoma, the relative proportions of total T lymphocytes and CD4- or CD8-expressing (helper or cytotoxic) T lymphocyte subsets were determined by immunohistochemistry. RESULTS: When the invasive carcinoma stromal infiltrate was compared with the infiltrate of preinvasive lesions, the numbers of total T cells and the CD8-positive subset increased significantly in the invasive cancers (P < 0.005). Although immunocyte infiltrates were highly concentrated in focal clusters beneath the preinvasive squamous lesions, the CD8-positive immunocytes diffusely infiltrated the invading tumor. CONCLUSIONS: The CD8-positive T cell infiltrate far exceeded the CD4-positive cells in the invasive, but not in the preinvasive lesions, a finding that suggests that CD8 cells are recruited preferentially to cervical lesions with progression to invasion.

The current status of the Papanicolaou smear.

Since its introduction as a screen for cervical cancer in the late 1940s, the Pap smear has become one of the most widely accepted screening procedures for cancer. Numerous scientific studies have now attested to its effectiveness. However, important issues related to the Pap smear, including cytologic nomenclature, accuracy, regulatory procedures, and screening guidelines, are still being evaluated and debated. This article provides an overview of important issues related to the Pap smear.

Adenocarcinoma of the endometrium: survival comparisons of patients with and without pelvic node sampling.

From 1969 to 1990, 649 patients with adenocarcinoma of the endometrium were surgically managed by gynecologic oncologists from the University of Alabama at Birmingham. All patients underwent TAH-BSO and washings. Two hundred twelve patients had multiple-site pelvic node sampling (mean number of nodes, 11), 205 patients had limited site pelvic node sampling (mean number of nodes, 4), and in 208 patients, nodes were not sampled. Historical prognostic features, including tumor grade, depth of invasion, adnexal metastasis, cervical involvement, and positive cytology, were equally distributed in the three groups. Mean follow-up was 3 years. Patients undergoing multiple-site pelvic node sampling had significantly better survival than patients without node sampling (P = 0.0002). When patients were categorized as low risk (disease confined to the corpus) or as high risk (disease in the cervix, adnexa, uterine serosa, or washings) multiple-site pelvic node sampling again provided a significant survival advantage compared to patients without node sampling (high risk, P = 0.0006; low risk, P = 0.026). In a comparison of patients receiving whole pelvic radiation for grade III lesions or deep myometrial invasion, patients with multiple-site pelvic node sampling had better survival than those in whom nodes were not sampled (P = 0.0027). The significant survival advantage for patients having multiple-site node sampling, overall and in high- and low-risk groups, strongly suggests a therapeutic benefit. Additionally, adjuvant therapy may be more appropriate directed in these patients.

LLETZ is an acceptable alternative to diagnostic cold-knife conization.

Large loop excision of the transformation zone (LLETZ) provides a pathologic specimen similar to a cold-knife cone (CKC) biopsy of the cervix. One hundred twenty women with indications for a cone biopsy were evaluated with LLETZ to determine if this procedure is an acceptable alternative to traditional cold-knife conization of the cervix. All patients had LLETZ performed in the clinic under local anesthesia. An average of 2.1 slices was required to remove the transformation zone. Coagulation artifact interfered with histologic diagnosis in only 1.8% of specimens. The number of slices taken during the LLETZ procedure significantly correlated with the amount of heat artifact in the pathology specimen (P = 0.02) and interfered with the ability of the pathologist to determine complete excision of dysplasia (P = 0.03). LLETZ is an acceptable alternative to diagnostic CKC and can offer a substantial cost savings. To facilitate histopathologic interpretation, every effort should be made to minimize the number of slices and to maintain orientation of the LLETZ specimen. Endocervical curettage performed after LLETZ can identify a group of patients who are at high risk for CIN recurrence.

Prospective randomized trial of LLETZ versus laser ablation in patients with cervical intraepithelial neoplasia.

Three hundred seventy-five patients with CIN on referral Pap and with a distinct cervical lesion on colposcopy were prospectively randomized to treatment with LLETZ or to standard colposcopic evaluation with directed cervical biopsies, endocervical curettage, and laser ablation of the transformation zone for biopsy proven CIN. Of the 195 patients that randomized to treatment with LLETZ, 32.5% had no evidence of dysplasia, 26.5% had CIN 1, 17.3% had CIN 2, 22.7% had CIN 3, and 0.5% had microinvasive carcinoma on final histologic evaluation. Of the 180 patients randomized to laser ablation, initial cervical biopsies demonstrated no evidence of dysplasia in 52.8% of patients, CIN 1 in 22.0%, CIN 2 in 18.3%, and CIN 3 in 5.7%. Only 114 (63.3%) of the women in the laser group required therapy. Complications were comparable for each treatment arm. Only 6.7% of patients randomized to LLETZ and 4.4% with laser ablation had persistent CIN on follow-up Pap. LLETZ appears to be effective, well tolerated, and less expensive, but the cost savings advantage of LLETZ over laser ablation may not apply to patients with CIN 1 on referral Pap smear since many do not require treatment.