Endometrial carcinoma recurrence according to race and ethnicity: An NRG Oncology/Gynecologic Oncology Group 210 Study.

Non-Hispanic black (NHB) women are more likely to experience an endometrial carcinoma (EC) recurrence compared to non-Hispanic white (NHW) women. The extent to which tumor characteristics, socioeconomic status (SES) and treatment contribute to this observation is not well defined. In the NRG Oncology/Gynecology Oncology Group (GOG) 210 Study we evaluated associations between race/ethnicity and EC recurrence according to tumor characteristics with adjustment for potential confounders. Our analysis included 3,199 NHW, 532 NHB and 232 Hispanic women with EC. Recurrence was documented during follow-up. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between race/ethnicity and EC recurrence in models stratified by histologic subtype (low-grade endometrioid, high-grade endometrioid, serous, mixed cell, carcinosarcoma, clear cell) or stage (I, II, III) and adjusted for age, SES, body mass index, smoking status and treatment. In histologic subtype-stratified models, higher EC recurrence was noted in NHB women with low-grade endometrioid (HR = 1.94, 95% CI = 1.21-3.10) or carcinosarcomas (HR = 1.66, 95% CI = 0.99-2.79) compared to NHWs. In stage-stratified models, higher EC recurrence was noted among NHB women with stage I (HR = 1.48, 95% CI = 1.06-2.05) and Hispanic women with stage III disease (HR = 1.81, 95% CI = 1.11-2.95). Our observations of higher EC recurrence risk among NHB and Hispanic women, as compared to NHW women, were not explained by tumor characteristics, SES, treatment or other confounders. Other factors, such as racial differences in tumor biology or other patient factors, should be explored as contributors to racial disparities in EC recurrence.

Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors.

A monoclonal antibody to human estrogen receptor protein (H222 Sp gamma), amplified via immunoperoxidase techniques, was used in the analysis of estrogen receptor in 452 breast carcinomas, 100 endometrial carcinomas, and 15 melanomas. Immunohistochemical evaluation incorporated both intensity and distribution of staining (HSCORE). Quantitative estrogen receptor content was determined by dextran-coated charcoal analysis and sucrose density gradient analysis. In all cases H222 Sp gamma localized in the nucleus of target cells. A semiquantitative correlation existed between HSCORE and biochemical assays for breast and endometrial tissues. The sensitivities and specificities for HSCORE as compared to the biochemical assays ranged from 80 to 95% and from 74 to 94%, respectively. HSCORE correlated with tumor grade for breast and endometrial carcinoma. Immunohistochemical evaluation showed no specific staining in melanomas. The data suggest that immunohistochemical receptor localization provides information complementary to standard biochemical assays in the tissues studied.

Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody.

Immunohistochemical localization of estrogen receptor (ER) using specific monoclonal anti-human estrogen receptor antibody, H222, with an immunoperoxidase technique was performed on fresh frozen tissue derived from 100 endometrial adenocarcinomas. Immunohistochemical evaluation incorporated both intensity and distribution of staining. In all cases, H222 localized in the nucleus of target cells. A significant quantitative relationship was shown between histological score (H-Score) and the biochemical analysis of ER content in tissue homogenates (r = 0.65, P = 0.00001). Excellent sensitivity (92%) and specificity (93%) were observed for the comparison of H-Score to the biochemical assay. Significant ER localization was present in stromal and myometrial elements, component H-Score of which correlated weakly with component H-Scores of malignant epithelial elements. Divergent receptor localization in stromal and myometrial versus malignant epithelial elements suggests that biochemical assays of endometrial carcinoma specimens may not reflect cancer-relevant receptor content. The data presented here suggest that the immunoassay of ER using H222 monoclonal antibody provides additional histochemical information to complement conventional analyses of endometrial adenocarcinomas.

Ovarian cancer screening.

PURPOSE: To review potential screening tools of early ovarian cancer and the associated risk factors for the development of ovarian carcinoma. DESIGN AND RESULTS: A review of pertinent literature was conducted, restricted to English-language published reports, book chapters, and articles. The value of serum tumor markers, particularly CA 125, ultrasound, transabdominal and transvaginal ultrasonography, and transvaginal color Doppler imaging as screening tools for ovarian cancer was assessed. CONCLUSION: Based on the literature, a large-scale long-term study that compares the mortality rates of a screened versus unscreened patient population is required before the efficacy of any screening method can be determined definitively.

Hydroxyurea versus misonidazole with radiation in cervical carcinoma: long-term follow-up of a Gynecologic Oncology Group trial.

PURPOSE: Long-term follow-up data of a randomized trial that compared hydroxyurea and the hypoxic-cell radiosensitizer to misonidazole as adjuncts to standard radiation therapy in locally advanced carcinoma of the cervix are reported. PATIENTS AND METHODS: Three hundred eight women were entered, and all 294 eligible patients are assessable as randomized. Eighty-one percent of patients have been monitored for 5 years or to death. RESULTS: There was an advantage for hydroxyurea in progression-free interval and survival (P = .05 and P = .066, respectively). There was no significant difference in the distribution of sites of failure between the regimens. For the 39% of patients with stages III to IVA disease, the advantage in progression-free interval for hydroxyurea was significant (47.8% v 33.6%). More leukopenia occurred on the hydroxyurea regimen than on the misonidazole regimen. CONCLUSION: In summary, these data provide stronger evidence than our previous analysis that hydroxyurea is superior to misonidazole as an adjunct to radiation therapy. For patients with locally advanced carcinoma of the cervix, hydroxyurea continues to be the adjunct of choice with radiation.

Assessment of dose-intensive therapy in suboptimally debulked ovarian cancer: a Gynecologic Oncology Group study.

PURPOSE: We report a prospective randomized trial in women with advanced ovarian cancer to evaluate the importance of chemotherapy dose-intensity on survival, progression-free survival (PFS), and response. PATIENTS AND METHODS: A total of 485 patients with epithelial ovarian cancer and residual masses more than 1 cm following surgery (stage III presentation) or any stage IV presentation were randomly assigned to receive either standard therapy (cyclophosphamide 500 mg/m2 and cisplatin 50 mg/m2 intravenously every 3 weeks for eight courses) or intense therapy (cyclophosphamide 1,000 mg/m2 and cisplatin 100 mg/m2 intravenously every 3 weeks for four courses). Dose modification was rigidly controlled to maintain intensity. Clinical and pathologic responses were assessed, when appropriate, as well as PFS interval and survival. RESULTS: A total of 458 patients met all eligibility criteria and were assessed for survival and PFS. The dose-intensive group received the same total dose of cyclophosphamide and cisplatin, but 1.97 times greater dose-intensity than the standard group. Clinical and pathologic response rates; response duration, and survival were similar in both groups of patients. Hematologic, gastrointestinal, febrile episodes, septic events, and renal toxicities were significantly more common and severe in the dose-intensive group. CONCLUSION: A doubling of the dose-intensity in the treatment of bulky ovarian epithelial cancers led to no discernible improvement in patient outcome and was associated with more severe toxicity. This study provides no evidence to support the hypothesis that modest increases in dose-intensity without increasing total dose are associated with significant improvement in overall survival or PFS.

A randomized comparative trial of carboplatin and iproplatin in advanced squamous carcinoma of the uterine cervix: a Gynecologic Oncology Group study.

A total of 394 patients with advanced, measurable squamous carcinoma of the uterine cervix and no prior chemotherapy were randomized to therapy with either carboplatin or iproplatin. There were 23 patients ineligible for the study and 10 patients who were not evaluable; the remaining 361 patients were evaluable for response and adverse effects. Randomization was well balanced for age, performance status, and prior therapy. Both platinum analogs were given every 28 days with starting doses of 400 mg/m2 for carboplatin (340 mg/m2 if the patient underwent prior radiation) and 270 mg/m2 for iproplatin (230 mg/m2 if the patient underwent prior radiation). These doses are equivalent to cisplatin doses of 75 to 100 mg/m2. Hematologic toxicity was dose-limiting, among which thrombocytopenia was slightly more common than leukopenia. Gastrointestinal toxicity was also prominent with both agents; however, iproplatin was significantly more toxic than carboplatin (P less than .001). Renal, otic, and peripheral nervous system toxicities were absent or infrequent with both analogs. No electrolyte abnormalities were observed. The percentage of planned dosages that were actually administered was 100% of carboplatin doses and 85% of iproplatin doses (P less than .0001). The reduction in iproplatin dose was apparently due to gastrointestinal toxicity. Response rates were similar for both agents (15% for carboplatin, 11% for iproplatin) and appear to be inferior to those noted with the parent compound, cisplatin.

Endometrial cancer: incidence, prognostic factors, diagnosis, and treatment.

Endometrial cancer is the most common gynecologic malignancy seen in the United States. Risk factors include unopposed estrogen (both endogenous and exogenous). Since tamoxifen is said to have weak estrogen activity, it has been suggested that tamoxifen may cause endometrial cancers. Of the 15 studies reported (clinical trials, prevalence, cross-sectional, and case control), 12 showed no relationship, two noted an increased incidence of endometrial cancer, and one noted a decreased incidence. When one considers the increased incidence of endometrial cancer in breast cancer patients, potential surveillance and ascertainment bias, latency, and occult endometrial cancers, it appears that there is a very small, if any, association of tamoxifen and endometrial cancer. In the asymptomatic patient on tamoxifen, routine yearly gynecologic examinations are recommended. Special studies to evaluate the endometrium do not appear to be indicated in the asymptomatic patient.

Cancer and pregnancy.

Carcinoma of the cervix is the most frequently diagnosed cancer in pregnancy. Still, it is an unusual situation. An abnormal Pap smear during pregnancy is a much more common occurrence and fortunately one that can be managed conservatively. Although definitive treatment for intraepithelial disease can be delayed until the postpartum period, diagnostic evaluation should be done when the abnormal Pap smear is present. Invasive cancer management is dependent on gestational age of the fetus. Pregnancy affords an excellent opportunity to screen for cervical neoplasia.

Estrogen replacement therapy: is previously treated cancer a contraindication?

The benefits of estrogen replacement therapy in preventing vasomotor symptoms, osteoporosis, and cardiovascular disease are well documented. Although estrogen is said to be contraindicated in patients successfully treated for endometrial and breast cancer, there are no data to substantiate this admonition. Experience suggests that it can be used safely in patients treated previously for endometrial cancer. Although there is little or no experience with estrogen use in the woman treated previously for breast cancer, circumstantial evidence suggests that it is not contraindicated in all such cases. Informed consent, patient desires, and risk-benefit considerations must enter into the decision to use estrogen in these patients.

Cryotherapy in the treatment of cervical intraepithelial neoplasia.

More than ten years of experience has now accumulated relating to the treatment of cervical intraepithelial neoplasia (CIN) by cryocautery. Cryotherapy has been established as an acceptable and effective therapeutic approach to CIN. Careful safeguards must be defined and respected to avoid the failure of diagnosing invasive carcinoma at the outset and to detect and manage persistent disease during follow-up. A treatment failure rate must be anticipated, but this failure rate does not appear excessive and is indeed comparable to that realized with other conservative forms of therapy. Presently, there appears to be no valid reason for proscribing or limiting the use of cryocautery in the treatment of CIN.

Diagnosis of deep venous thrombosis in obstetrics and gynecology by impedance phlebography.

The accurate diagnosis of deep venous thrombosis is fundamental in reducing the morbidity and mortality from thromboembolism in obstetrics and gynecology. This is the first report of the use of a noninvasive diagnostic technique, occlusive cuff impedance phlebography (IPG), on an obstetric and gynecologic service. One hundred sixteen patients were examined by IPG with an overall diagnostic accuracy of 95.6% (sensitivity, 87.5%; specificity, 93.8%). Ninety-one patients had symptoms suggestive of deep venous thrombosis, but this diagnosis was confirmed in only 26.3%. The use of IPG to screen high-risk patients prospectively and evaluate patients with pulmonary emboli is discussed. IPG is ideally suited as a diagnostic method in obstetrics and gynecology because it is accurate, noninvasive, and nonradiologic, and it may be performed at the patient's bedside.

Papanicolaou smear history of patients developing cervical cancer: an assessment of screening protocols.

The American Cancer Society recently has suggested changes in the frequency of Papanicolaou smear screening which, if followed, would alter current practice considerably. This study assessed the impact of the Papanicolaou smear screening interval on the prevention of advanced disease. Between July 1, 1980 and June 30, 1984, 264 women were evaluated and treated for primary epithelial carcinoma of the cervix (64% had stage I disease). Ninety-seven women (37%) had had a normal Papanicolaou smear within three years of diagnosis, including 48 women (18%) whose last normal Papanicolaou smear was within a year of diagnosis. The cytologic history was unavailable for 81 women (31%). Patients with a screening interval of greater than six years were more likely to be older, of lower socioeconomic status, and black, as compared with patients in the more frequently screened groups. Patients with a screening interval of 36 months or less were similar to those with a 37- to 72-month interval with respect to age, racial characteristics, and socioeconomic status. In this similar group of patients, a screening interval of 37-72 months was associated with a significantly larger proportion of advanced stage disease than found in more frequently screened patients. A policy of screening more frequently than every three years may therefore lead to increased survival among women who develop cervical cancer despite cytologic screening.

Estrogen replacement therapy in the patient treated for endometrial cancer.

Adenocarcinoma of the endometrium is considered to be an estrogen-dependent neoplasia and as such, hormone replacement therapy is said to be contraindicated. The authors are unaware of any data to substantiate that statement. Patients, who had completed their therapy for stage I carcinoma of the endometrium, were placed on estrogen hormone replacement therapy in a nonrandomized fashion. Between 1975 and 1980, 221 patients with stage I adenocarcinoma of the endometrium were managed at the Duke University Medical Center. Forty-seven patients received estrogen after their cancer therapy, whereas 174 patients did not. Risk factors for recurrence were similar between the two groups. After controlling for these known risk factors, the estimated distributions of time to recurrence for the two groups were significantly different (P less than .05), with the estrogen group experiencing longer disease-free survival. The history of endometrial cancer does not appear to be a contraindication to hormone replacement therapy in patients with stage I disease.

Thromboembolism complicating surgery for cervical and uterine malignancy: incidence, risk factors, and prophylaxis.

Venous thromboembolism is a leading cause of death and morbidity after extended surgery for early malignancies of the cervix and uterus. Two hundred eighty-one patients who underwent such surgery were retrospectively evaluated for associated risk factors, the incidence of clinically significant thromboembolic complications, and prophylactic value of low-dose heparin and antiembolism stockings. Significant thromboemboli were encountered in 7.8% of patients postoperatively and accounted for the only 4 postoperative deaths. Forty-five percent of patients who developed thromboemboli did so after discharge from the hospital. The preoperative risk factors found to be associated with thromboembolism, in order of statistical significance, were weight in excess of 85.5 kg, advanced clinical stage of malignancy, and radiation therapy within 6 weeks of the operative procedure. Low-dose heparin therapy and the use of antiembolism stockings as preventative measures did not appear to reduce the incidence of thromboembolic complications. A prospective study will be necessary to evaluate definitely the effectiveness of various therapeutic modalities on thromboembolism in gynecologic oncology patients.

Cytopathology and the management of early invasive cancer of the uterine cervix.

This study was designed to review the effectiveness of cytopathology as it entered into the evaluation of patients with possible microinvasive or early occult carcinoma of the uterine cervix. During the 7-year period of 1971 to 1977, 39 consecutive patients were found for whom either a cytopathologic diagnosis of early invasive carcinoma had been made or suggested, or a histopathologic diagnosis of early invasive carcinoma had been made. After review, 35 patients had an ample number of cytopathologic and histopathologic materials and clinical records to be included in the study. The results of these studies have shown that when cytopathology on review predicted a lesion more severe than carcinoma in situ, it was confirmed by histopathology in more than 78% of patients (22 of 28 cases). In those patients shown by histopathology to have microinvasive or occult invasive carcinoma, the cytopathology reflected it in 87% of patients (27 of 31 cases). In the cases of histologically proved microinvasive carcinoma, the corresponding genital smears either diagnosed or suggested invasive carcinoma in 81% of cases and carcinoma in situ in 19%. From these studies it has been concluded that diagnostic cytopathology is potentially a highly reliable tool when used in conjunction with other modern diagnostic modalities to aid the decision-making in cases of probable early cancer of the uterine cervix.

Pyometra. A complication of cervical cryosurgery.

PIP: In a series of 300 patients at the Duke University Medical Center cryosurgery was performed in cases of abnormal cytology indicative of preinvasis cervical disease. Colposcopy and biopsies were done before freezing. Only minor complications had followed until recently 2 patients developed pyometra within 72 hours after cryosurgery. Both had a previous history of pelvic inflammatory disease. Each had an intrauterine device (IUD) in place. In 20 other patients with IUDs no complications had occurred. An additional 4 patients had an acute exacerbation of pelvic infections during the 1st week after cryosurgery. None were wearing an IUD. Patients with a history of repeated gonococcal infections had residual mixed anaerobic infections are not considered suitable for cryosurgery. Pelvic inflammatory disease may be aggravated by this technique. Pyometra as a side effect may result.^ieng

Cryosurgery in the management of cervical intraepithelial neoplasia.

Cryosurgery is an outpatient modality capable of destroying cervical intraepithelial neoplasia (CIN). Among 770 patients treated with cryosurgery who had at least two follow-up Papanicolaou smears, a persistence of CIN was noted in 10%. It was more difficult to destroy CIN III disease and large lesions (more than 50% of the cervix involved), although grade appeared to be more important than size of the lesion. Many patients with a persistent lesion were retreated as outpatients; as a result, in more than 96% of the 770 patients the lesion was eradicated.

Epithelial ovarian tumors of low malignant potential.

The records of 31 women with ovarian tumors of low malignant potential were retrospectively reviewed to identify factors that determine the prognosis. Median follow-up was 51 months. Eighteen women had stage I disease. Twenty-three women (74%) had serous tumors, of which 46% were bilateral. Nine patients (29%) had concomitant endometriosis or endosalpingiosis. Two patients died of disease; both had mucinous tumors with extraovarian metastases at initial operation and inadequate pathologic sampling of their tumors. These results were combined with those of 970 women identified in previous reports to show that the rate of recurrence or persistence of ovarian tumors rises from 2% for women with stage I disease to 14% for those with stage III or IV disease, while mortality rises from 2 to 5%. Careful staging and pathologic sampling are important for establishing the prognosis. Testing of adjuvant therapy should be limited to patients with extraovarian disease.