A randomized trial of adjuvant progestagen in early endometrial cancer.

A randomized, controlled trial was designed to determine whether adjuvant progestagen therapy improves survival in patients with Stage I or Stage II endometrial cancer. After surgery, 1148 patients were randomly assigned to adjuvant treatment with progesterone or were given no additional therapy. The duration of follow-up ranged from 42 to 132 months (median follow-up, 72 months). Crude survival and relapse rates were similar for both groups. Death due to intercurrent disease was higher in the progesterone group (P = 0.04). The median survival of the group of patients with cancer-related death was higher in the progestagen group than in the control group (30 and 22 months, respectively; P = 0.03). In 461 high-risk patients, a tendency towards fewer cancer-related deaths and a better disease-free survival in the treatment group was observed, but crude survival was unchanged. We conclude that there is little to gain from adjuvant progestagen therapy in patients with low-risk endometrial cancer, and that further studies are needed in high-risk patients.

Follow-up study of 232 patients with stage Ia1 and 411 patients with stage Ia2 squamous cell carcinoma of the cervix (microinvasive carcinoma).

This report retrospectively analyzes 643 patients with microinvasive squamous cell carcinoma of the cervix who were followed-up for 3-17 years. The cases were classified according to the FIGO definition adopted in 1985 which includes a subdivision into Stage Ia1 and Stage Ia2. It is concluded that the new FIGO system has definite advantages for the decision of therapy in microinvasive carcinoma. Unnecessary radical treatment can be avoided.

[Cervical intraepithelial neoplasia. Terminology, diagnosis and treatment]. / Cervikal intraepitelial neoplasi. Terminologi, diagnose og behandling.

Today cervical intraepithelial neoplasia (CIN I-III) is the most commonly used term for lesions which in earlier years were called dysplasia and carcinoma in situ. The introduction of cytologic smears in the 1960s resulted in a sharp increase in the number of such lesions reported to the Cancer Registry of Norway. Each year close to 900 new cases are registered. Diagnosis and treatment are strongly dependent on colposcopy and endocervical curettage. Ectocervical lesions may well be treated by destructive methods such as cryosurgery, cold coagulation, electrocoagulation diathermy or laser vaporization. For lesions extending up into the endocervix, conisation is the best method, preferably performed by laser. A series of 171 cases of CIN I-III reported during the years 1953-86 shows that invasive cancer may occur also with free margins on the cone, and as long as 10-20 years after primary treatment. Careful and almost life-long follow-up is therefore essential.

Misonidazole combined with radiotherapy in the treatment of carcinoma of the uterine cervix.

Between April 1979 and January 1982, 331 patients were included in a study to establish whether misonidazole (MISO) had any effect as an adjuvant to radiotherapy in the treatment of squamous cell carcinoma of the uterine cervix (FIGO Stage IIb, III, and IVa). Patients were randomized to receive either MISO (12 g/m2 applied within 6 weeks) or placebo. This was given in conjunction with each institution's normal radiotherapy schedule and thus varied with regard to external and intracavitary irradiation. The analysis was performed based on patients' status at January 1986, with all patients observed for at least 4 years. One hundred and sixty-four patients received MISO and 167 placebo. Compliance to radiotherapy was good and MISO was well tolerated. The overall rates for MISO vs. placebo were as follows: local tumour control, 50 vs. 54%; disease-free survival, 47 vs. 46%, and crude survival, 39 vs. 45%. A similar lack of MISO effect was found in the individual stages. However, patients in all stages with hemoglobin concentrations below 7 mmol/l had a significantly lower local control probability (overall 24 vs. 47%), whereas the incidence of distant metastases was unaffected. We conclude that the addition of MISO did not influence the radiation response in advanced uterine carcinoma. The reasons for this ineffectiveness are yet to be clarified.

[Preserving ovarian function in the treatment of epithelial and special (other) malignant ovarian tumors]. / Erhaltung der Ovarialfunktion in der Behandlung der epithelialen und speziellen (anderen) malignen Ovarialtumoren.

About 90% of malignant tumors of the ovary in Scandinavia develop from the germinal epithelium. There are great differences in the incidence rates between countries in the Western world and in Africa and Asia. The WHO classification of ovarian malignancies is generally used. The epithelial tumors comprise the serous, mucinous, endometrioid, clear cell, undifferentiated and mixed true carcinomas. In addition, borderline lesions of especially the serous and mucinous types are of interest when the question of preservation of ovarian function comes into notice. Conservative surgery, which means removal of only the afflicted ovary should be restricted to young women of the childbearing age who want to preserve the possibility of becoming pregnant. However, certain prerequisites must be fulfilled. The tumor must be located to one ovary only (Stage Ia) and must be either a borderline lesion or a Grade 1 true carcinoma of either the serous, mucinous or endometrioid type. There must be no ascites and peritoneal washings must be negative for cancer cells. Germ cell tumors are usually found in young women. Only the dysgerminomas are regularly bilateral in 10-15% of the cases. All other germ cell tumors are rarely bilateral. But both in borderline lesions, Grade 1 true carcinomas, and in germ cell tumors, a biopsy of the normal looking contralateral ovary should always be performed. Endodermal sinus tumors and immature teratomas may well be treated conservatively by surgery, but modern triple chemotherapy (VAC, PVB) must be added. Granulosa theca cell tumors are bilateral in only about 5% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical (stage III) as compared to subclinical intrapelvic extrauterine tumor spread in endometrial carcinoma: a clinical and histopathological study of 175 patients.

One hundred and seventy-five patients with endometrial cancer, seen in the Norwegian Radium Hospital from 1960 to 1977, had tumor extension outside the uterus but not outside the true pelvis. One hundred and eight of these patients had clinical stage III disease and in 67 patients, originally classified as stage I or stage II, the intrapelvic extrauterine tumor spread was first detected at surgery or at histopathological examination of the operation specimen. The 40% 5-year-actuarial survival of the latter group differed significantly from the 16% found in clinical stage III (P less than 0.001). This must be largely contributed to the fact that radical surgery could only be performed in 13% of the clinical stage III group as compared to 70% in the group of patients with subclinical extrauterine disease. Surgical eradication of all macroscopic tumor was of major prognostic importance for patients with clinical stage III, resulting in an actuarial 5-year survival of 41%, nearly identical to 42% for the group of patients with subclinical extrauterine tumor extension. Adjuvant progestagen therapy seemed to be of some benefit, but the need, however, for a more effective systemic treatment, possibly using cytotoxic drugs, is evident.

Stage IV endometrial carcinoma: a clinical and histopathological study of 83 patients.

From 1960 to 1977, eighty-three patients with stage IV endometrial carcinoma were treated in the Norwegian Radium Hospital. The lung was the main site of extrapelvic tumor extension (36%), followed by "multiple sites" (23%), lymph nodes (inguinal, supraclavicular, axillar; 13%), and bladder (13%). The actuarial 5-year-survival rate was 10%. Complete clinical remission was achieved in 5 patients with lung metastases, in 2 with inguinal lymph node metastases, and in 1 patient with ascites with positive cytology. Control of pelvic disease could be achieved in 20 of 72 patients (28%) by radiotherapy alone or combined with surgery and/or progestagens. Progestational agents proved to be of benefit especially for patients with lung metastases. A complete remission of all visible lesions was observed in 8 out of 26 patients (31%). Patients with well- and moderately differentiated primary adenocarcinoma had a response rate of 83% as opposed to 14% for patients with poorly differentiated adenocarcinomas and adenosquamos carcinomas. Extrapelvic tumor localizations, suitable for radiotherapy, were supraclavicular and axillary lymph nodes and bone metastases.

Recurrent adenocarcinoma of the endometrium: a clinical and histopathological study of 379 patients.

Three hundred and seventy-nine patients with recurrent endometrial cancer were seen in the Norwegian Radium Hospital from 1960 to 1976. Local recurrence was found in 190 patients (50%), distant metastases in 108 patients (28%), and in 81 patients (21%) local recurrence and distant metastases were found simultaneously. Thirty-two percent of all patients had no symptoms at the time of diagnosis of the recurrence. The median time interval between primary treatment and detection of recurrence was 14 months for patients with local recurrence and 19 months for those with distant metastases. Thirty-four percent of all recurrences was detected within 1 year and 76% within three years of primary treatment. In 10% recurrence was diagnosed more than 5 years after primary treatment. Twenty-two of the 190 patients (12%) with local recurrence, 5 of the 108 patients (5%) with distant metastases, and 2 of the 81 patients (2%) with local recurrence together with distant metastases survived and were without evidence of disease at the end of the observation period (3-19 years). Radiotherapy alone or in combination with surgery was given in 24 of the 29 "cured" patients; 16 of them received progestagens in addition. Three of the survivors were treated with progestagens alone. The median survival time for patients with lung metastases only, who were treated with progestagens, was considerably longer when compared to those without treatment (9 vs 2 months). The need for nonhormonal cytotoxic chemotherapy in the treatment of recurrent endometrial carcinoma is stressed.

The effect of surgery and chemotherapy on blood NK cell activity in patients with ovarian cancer.

The cytotoxic activity of NK cells in peripheral blood was studied in 15 patients with ovarian cancer Stage III and IV before and after surgery and ten-week intramuscular therapy with thiotepa. An evident decrease in NK activity was found 24 hours after surgery, with a slow return toward normal values within 7-9 days. No differences between patients with explorative laparotomy and with extirpation of the tumor were observed. The mechanism of the decreased NK cytotoxicity remains unknown but there was a concomitant reduction in the number of blood mononuclears. A second drop in NK activity occurred after chemotherapy. It was most likely due to the drug bone marrow depression. No evident correlation between the reduced NK activity and advancement of the disease could be found.

Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients.

From 1968 to 1974, 540 patients with stage I adenocarcinoma of the corpus uteri entered a prospective clinical trial to evaluate the effect of postoperative external pelvic irradiation. After primary surgery all patients received intravaginal radium irradiation; 6000 rads was delivered to the surface of the vaginal mucosa. At the time vaginal radium was given, randomization was performed: Group A received no further treatment (controls); group B received additional high-voltage irradiation to the pelvic field with a dose of 4000 rads to the pelvic lymph nodes. During the follow-up period of 3 to 10 years a significant reduction in vaginal and pelvic recurrences was found in group B as compared with group A (1.9 versus 6.9%, P < .01). On the other hand, more patients in group B developed distant metastases than those in group A (9.9 versus 5.4%). Thus, the 5-year survival rate was not improved by external irradiation. A more detailed analysis of the series led to the conclusion that only patients with poorly differentiated tumors (grade 3), which infiltrate more than half the myometrial thickness, might benefit from additional external radiotherapy. In almost 20% of 151 consecutive patients, tumor cells were found in endothelial lined spaces. Significantly more deaths and recurrences were found among these patients compared to those without vessel invasion (26.7 versus 9.1%, P < .01).

Stage IB carcinoma of the cervix, the Norwegian Radium Hospital, 1968-1970: results of treatment and major complications. I. Lymphedema.

Different methods of treatment have been debated over the years for Stage IB carcinoma of the cervix, especially in view of the results and complications. We have reviewed the experience of the Norwegian Radium Hospital for carcinoma of the cervix, Stage IB, for the years 1968, 1969, and 1970; most of the patients receive preoperative intrauterine and intravaginal radium, followed by radical hysterectomy and pelvic lymphadenectomy; if the nodes are involved, they also receive external pelvic irradiation. During this period, 437 patients had Stage IB; the 5 year survival was 80.2% (not corrected). We focused our attention on lymphedema following such a method of treatment; of 402 patients operated upon, 23.4% developed lymphedema ranging from mild to moderate to severe; 20 patients (5%) had severe lymphedema; factors involved are analyzed.

Postoperative irradiation and chemotherapy in patients with advanced ovarian cancer.

Two groups of patients with stage III ovarian carcinoma were selected for a randomized clinical trial. The first group consisted of 157 patients who had radical surgery at their first laparotomy, the second group consisted of 145 patients with inoperable disease. The aim of the trial was to compare the results of maximum external megavoltage irradiation, 5 000 rads, to a large abdominal field, with the results of a reduced dose, 3 000 rads, immediately followed by chemotherapy with an alkylating agent (Thio-tepa). In none of the groups, did maximum radiotherapy prove superior to the schedule of a reduced dose combined with chemotherapy. The less costly and time saving combined treatment was better tolerated than irradiation alone. Histological tumour type did not influence the prognosis in these advanced cases where spread was found outside the true pelvis.