William T. Creasman

Surgical pathologic spread patterns of endometrial cancer: A gynecologic oncology group study

The surgical pathologic features of 621 patients with Stage I carcinoma of the endometrium are presented. All patients were treated with primary surgery consisting of total abdominal hysterectomy, bilateral salpingo‐oophorectomy, selective pelvic and paraaortic lymphadenectomy and peritoneal cytology. An appreciable number of patients (144—22%) with Stage I cancers have disease outside of the uterus (lymph node metastasis, adenexal disease, intraperitoneal spread and/or malignant cells in peritoneal washings). Multiple prognostic factors particularly grade and depth of invasion are related to extrauterine disease. This study adds credence to the primary surgical approach with individualized postoperative therapy as indicated.

Effects of long-term estrogen replacement therapy

Two groups of hypoestrogenic women are analyzed by retrospective comparisons. Patients were observed by a single group of physicians for at least five years; 301 patients were treated with replacement estrogen and 309 patients were untreated. Incidence figures for various metabolic diseases present at entry and both during and after estrogen therapy were compared by the usual statistical analysis and by statistical adjustments for certain group differences (Mantel-Haenszel statistic). The long-term administration of estrogen to these relatively young women with hypoestrogenism was associated with significantly lower rates of development of cardiovascular disease, hypertension, osteoporosis, and fractures. Detrimental effects were a higher rate of abnormal uterine bleeding and an increase in the likelihood of developing adenocarcinoma of the endometrium. Effects of estrogen preparation, dosage, method of therapy, duration of therapy, and the addition of synthetic progestins are presented.

A prospective surgical pathological study of stage I squamous carcinoma of the cervix: A Gynecologic Oncology Group study

Thirty-three institutions collaborating in the Gynecologic Oncology Group gathered surgical and pathological data on 1125 patients with primary, previously untreated, histologically confirmed stage I cervical carcinoma with more than 3 mm of invasion who were selected to undergo radical hysterectomy and paraaortic and pelvic lymphadenectomy. Of the 940 eligible, evaluable patients, 732 had squamous carcinoma. Of the study group, 87 (12%) did not undergo radical hysterectomy because of gross disease beyond the uterus or microscopic aortic node involvement documented at exploratory laparotomy. Among the 645 patients undergoing pelvic and paraaortic lymphadenectomy and radical hysterectomy, five risk factors were significantly associated with microscopic pelvic lymph node metastasis: depth of invasion (P = 0.0001), parametrial involvement (P = 0.0001), capillary-lymphatic space invasion (P = 0.0001), tumor grade (P = 0.01), and gross versus occult primary tumor (P = 0.009). The factors identified as independent risk factors for pelvic lymph node metastasis by multivariate analysis were capillary-lymphatic space involvement (P less than 0.0001), depth of invasion (P less than 0.0001), parametrial involvement (P = 0.0005), and age (P = 0.02). The model was used to predict the chance of a patient having nodal metastasis for any combination of risk factors.

A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas

Various drug combinations including Adriamycin have been tested in soft tissue sarcomas, but optimal treatment remains unclear. We have evaluated Adriamycin with and without dimethyl‐triazeno‐imid‐azole‐carboxamide (DTIC) in the treatment of Stage III or IV and recurrent sarcomas of the uterus. Two hundred and forty cases of these rare tumors were evaluable. Of 146 evaluable patients with measurable disease, 13/80 (16.3%) of Adriamycin‐treated patients and 16/66 (24.2%) of patients receiving the combination showed an objective response (P > 0.05). Lung metastases responded more frequently (P = 0.04) to combination therapy, but there was no survival advantage. For patients with nonmeasurable disease the progression‐free interval was similar (10.0 months for Adriamycin and 8.0 months for the combination). Leiomyosarcomas had a significantly longer survival than other cell types (12.1 versus 6.0 months, P < 0.001) but there was no advantage for either regimen. There was a suggestion that heterologous mixed mesodermal sarcomas were more responsive to the combination (27.3 versus 8.7%). The addition of DTIC produced significantly more hematologic and gastrointestinal toxicity. Other Adriamycin combinations should be evaluated in uterine sarcomas.

Results and complications of operative staging in cervical cancer: Experience of the Gynecologic Oncology Group

Abstract A multiinstitutional study by the Gynecologic Oncology Group (GOG) has confirmed that clinical staging often is inaccurate in determining the extent of disease in patients with cervical cancer. The finding of positive paraaortic nodes in 29% of patients with Stage II, III, and IV tumors supports this conclusion. In this series, the incidence of paraaortic nodal metastases could not be correlated with the histologic grade of the tumors . With positive paraaortic nodes, conventional treatment limited to the pelvis can be expected to fail, but it is still not clear how many patients can be salvaged by treatment to extended paraaortic radiation fields . Longer periods of follow-up in patients whose treatment plans were based on surgical staging information will be required.

An alternate approach to early cancer of the vulva.

Early invasive squamous cell carcinoma of the vulva has emerged as a controversial issue in recent literature. Reports illustrating metastatic disease in the inguinal lymph nodes have conflicted with other reports suggesting local treatment only. The morbidity produced by radical vulvectomy to both body image and sexual function make this issue worthy of serious consideration. This report deals with an alternate approach to this disease entity which attempts to preserve vulvar tissue without sacrificing curability where possible metastatic disease exists. The concept is proposed of utilizing the superficial inguinal nodes as sentinel nodes in the treatment planning. The results of 20 patients treated in this manner are presented.

Risk factors and recurrent patterns in Stage I endometrial cancer

Clinical Stage I carcinoma of the endometrium was evaluated in 222 patients. Twenty-five percent of patients were found to have pathologic findings thought to require postoperative external irradiation; of these, 20 of 57 (35%) had recurrence. During the 36- to 72-month follow-up period, only 14 of 165 (8.3%) treated only with operation (68 patients or 31%) or operation plus intracavitary radium (97 patients or 44%) manifested a recurrence. Furthermore, of all recurrences, 27 of the 34 (79%) were outside the pelvis. In these surgically staged cases, the absence of definable, demonstrable extrauterine disease was associated with a 7% recurrence rate versus a 43% recurrence rate if disease was found anywhere outside the uterus. Recurrence and death were correlated with other prognostic factors, which are outlined in this report.

A randomized trial of cyclophosphamide and doxorubicin with or without cisplatin in advanced ovarian carcinoma. A Gynecologic Oncology Group Study.

A randomized clinical trial was conducted in women with bulky (suboptimal) Stage III and Stage IV ovarian carcinoma, using doxorubicin (Adriamycin) and cyclophosphamide with or without cisplatin. There were 440 evaluable cases, of which 227 had measurable disease. One hundred twenty of these latter patients were treated with cyclophosphamide and doxorubicin (CA), while 107 received cyclophosphamide, doxorubicin and cisplatin (CAP). The clinical complete response (CR) rate for CA was 26% (31/120) compared with 51% (55/107) for CAP (P = <0.0001). Of 23 CRs receiving CA who had a second‐look laparotomy, only four were negative; of 39 CRs receiving CAP and a second‐look, 13 were negative (not statistically significant). The response duration for patients with measurable disease (median 14.6 versus 8.8 months), progression‐free interval for all patients (13.1 versus 7.7 months), and survival for patients with measurable disease (19.7 versus 15.7 months) showed a statistically significant advantage for CAP; however, there was no difference in survival of patients with nonmeasurable disease. Toxicity was more severe with CAP but was tolerable. Thus, the addition of cisplatin improves the chemotherapy of advanced ovarian carcinoma.

Treatment of metastatic trophoblastic disease: Good and poor prognosis

Abstract This study reports results of therapy in 91 patients with metastatic gestational trophoblastic disease treated by physicians of the Southeastern Regional Trophoblastic Disease Center. The 91 patients were grouped into good (79 per cent) or poor (19 per cent) prognostic categories. “Poor prognosis” patients were identified by the presence of an initial pretreatment human chorionic gonadotropin (HCG) titer greater than 100,000 I.U. per 24 hours, duration of disease greater than 4 months, or the documentation of cerebral or hepatic metastases. The patients with “good prognosis” metastatic disease were all treated with systemic single agent chemotherapy with methotrexate or actinomycin D. Seventy of these 71 patients were cured. The poor prognosis patients were treated by two treatment protocols. The earlier group of 7 patients in this category were treated with combination chemotherapy only after resistance to conventional single agent methotrexate and actinomycin D had failed to cure the patient. Only one patient surviced. The later group of 10 patients with “poor prognosis” disease were initially treated with combination chemotherapy and 7 were cured. The roles of hysterectomy with chemotherapy, simultaneous liver and/or hepatic irradiation with chemotherapy, and arterially infused chemotherapy are discussed.

Effects of long-term estrogen replacement therapy: II. Neoplasia☆

Abstract Two groups of hypoestrogenic women are analyzed by retrospective comparison. Patients were observed by a single group of physicians for at least five years—301 patients treated with replacement estrogen and 309 untreated patients. Of each group, 207 women had uteri in situ. Incidence figures for neoplasia (gynecologic, breast, and all sites) were compared between the two groups and with the Third National Cancer Survey, yielding a risk ratio for the development of adenocarcinoma of the endometrium among estrogen-treated women of 3.8 and 9.3, respectively. There was no increase among any other malignancies. The addition of synthetic progestin to estrogen therapy provided significant protection against the likelihood of developing endometrial cancer and did not reduce previously reported metabolic benefits of estrogen treatment. Data pertaining to estrogen use and details of the patients with endometrial carcinoma are presented.