Fertility, pregnancy and cancer.

Results of clinical and experimental research into various aspects of cancer and pregnancy are reported. These investigations have been proceeding for many years. 845 cases of pregnancy with concomitant malignant tumor at various localization are reported here. Diagnostic methods and results of treating cervical and breast cancer during pregnancy are described. Also discussed is the influence of pregnancy on the clinical course of cancer and survival. Fertility after recovery from cancer accomplished by means of organ-preserving surgery is commented on.

PIP: This study describes the patterns of cervical and breast cancer among pregnant mothers who were treated at the NN Petrov Institute of Oncology in Russia during 1960-94. The sample included 476 patients admitted with invasive cervical cancer that was diagnosed during pregnancy or after birth or abortion. Findings were compared to a control group of 640 invasive cervical cancer patients and 240 breast cancer patients of reproductive age. 95.3% of cancers were malignant. 60.9% were tumors of the cervix, breast, and ovaries. The percentage of cervical cancer cases was 23.5% of reproductive age women. In 69% of the cervical cancer patients, the depth of tumor growth into the stroma exceeded 1 cm compared to only 32% in the control group. Cervical stage I cancer during pregnancy spread to the regional lymph nodes twice as frequently as in the control group. Lymphatic metastases were greatest in patients with regional metastases during the second and third trimester or after birth. 21.4% of pregnant patients and 15.5% of nonpregnant patients had stage III cervical cancer. 5-year survival rates after prompt treatment was 58.4% compared to 78.8% for controls. 2% of breast cancer patients were pregnant at the time of diagnosis, and most had the lobular form. Regional metastases were 1.5-2.0 times higher for breast cancer cases diagnosed during pregnancy compared to nonpregnant cases. The cancers diagnosed in the last two trimesters or during breast feeding tend to be aggravated. The 5-year survival rate is poor. The prognosis for the fetus is better if diagnosed in the third trimester, but better for the mother if diagnosed in the first trimester. Pregnancy does not increase the risk of malignant tumors and is not likely to accelerate tumor growth. IUD contraception should be used by breast cancer patients post-treatment. Cervical cancer patients should begin contraceptive use about 2 years after favorable prognosis.

[Effectiveness of radical therapy in vulvar carcinoma. An analysis of 148 cases]. / Zur Effektivität der radikalen Therapie des Vulvakarzinoms. Eine Analyse von 148 Fällen.

148 patients with primary squamous cell carcinoma of the vulva were treated by surgery at the N. N. Petrov-Cancer Research Institute St. Petersburg. There were 73 unilateral lesions confined to the labium majus or labium minus, 17 to labium majus and minus, 41 to the clitoris and 17 lesions to other structures. 28 patients had FIGO I lesion, 58 a FIGO II, and 62 patients had a FIGO III tumor. In 41 cases the depth of infiltration was 1-5 mm, in 83 cases 6-10 mm, and in 24 cases the depth of infiltration was greater than 11 mm. Radical vulvectomy with inguinal lymphadenectomy was performed in 115 cases, a simple vulvectomy in 33 cases (Nx). In 53 patients lymph nodes were positive and in 62 negative. The patients were followed for at least 60 month and none have been lost to follow-up. The stage dependent 5-year-survival rate was 96.4% (FIGO I), 87.7% (FIGO II), 62% (FIGO III), and 79.2% (overall). The 5-year-survival rate of lesions of the labium minus was 94.6%, of the labium majus was 83.1%, of the clitoris--82.2%. A poor prognosis was found in the cases of a tumor involvement in labium majus and minus and/or other vulvar structures (60% and 59.9%). Increasing depth of invasion was associated with decreasing 5-year-survival rate: 97.5% ($ 5 mm), 72.4% (6-10 mm) and 65.4% (> 11 mm). In patients with lymph node involvement the prognosis was significantly better than in those with negative lymph nodes (61.6% vs. 86%). On the other hand, the prognosis of patients with a solitary lymph node metastasis was significantly better than in patients with two or more lymph node metastasis (79.6% vs. 51.6%). Tumor localization, tumor size, lymph node status and especially the depth of invasion are the important prognostic factors in vulvar cancer.

Geographic peculiarities of endometrial and cervical cancer incidence in five continents (review).

The review of references and data on endometrial and cervical cancer incidence in five continents (1970, 1976, 1982, 1987) are presented. The increase in cervical cancer rates in the developing countries of Asia, Africa and Latin America has been recorded. The hormonedependent tumours (endometrial, breast cancer) prevail in the economically developed countries of Europe and North America. They have shown a tendency to increase since the end of the 70's. The possible causes of peculiarities in oncogynecological incidence have been discussed.

Treatment of patients with sarcoma of the uterus.

In the present series of 156 patients with sarcomas of the uterus the therapeutic modalities employed were evaluated. The 5-year survival rate of 51.3% was obtained for this series including 41.2% for leiomyosarcomas, 57.1% for endometrial stromal sarcomas, 50.0% for mixed mesodermal tumors and 40.0% for carcinosarcomas. The prognostic significance of the extent of disease, histological type and the age of patients is emphasised. Clinical features of uterine sarcomas specific for different histological types were shown: leiomyosarcomas were characterized by a rapid tumor growth while uterine bleeding in the background of neuroendocrine disturbances similar to those observed in endometrial carcinomas were related to endometrial stromal sarcomas and mixed mesodermal tumors. In respect to early diagnosis of sarcomas an ultrasonic pelvic examination and studies of aspirate specimens taken from the uterine cavity are recommended to be performed for the groups at high risk. An individual treatment policy was developed for each sarcoma patient depending on the histological type, the stage of disease and general condition of the patient. Surgical approach varied ranging from a total hysterectomy and adnexectomy, done for leiomyosarcomas, to an extended hysterectomy and pelvic lymphadenectomy for mixed mesodermal tumors and endometrial stromal sarcomas. Postoperative distant and/or endovaginal radiation are indicated for all histological types of sarcomas excepting leiomyosarcomas. Application of adjuvant chemotherapy with carminomycin or adriamycin improves the results of treatment.

Individualization of indications for postoperative irradiation in stage I endometrial cancer.

The results of the treatment of 550 Stages I-III endometrial cancer patients are analysed. The postoperative radiation therapy was employed in 311 (56.5 +/- 2.8%) patients. In the pathological Stage I 235 (50.5 +/- 3.2%) out of 465 women were irradiated postoperatively, but the distant irradiation was used in only 93 (20.6%), the others began prophylactic irradiation of vagina. With the aim of regression the nonparametric Cox model it was stated, that some factors, such as hormonosensitivity of the tumor, pathogenic type, histology, stage and mode of operation have a significant influence on survival, and the postoperative irradiation has not. The comparison of the results of treatment in Stage I revealed a slight tendency to increased survival in prognostically unfavourable subgroups with the aim of postoperative irradiation. The 5-year survival in Stage I 90.3%. The individualized indications for postoperative radiation therapy in Stage I endometrial cancer are elaborated deep myometrial invasion, lowering of differentiation of the tumors, hormonoresistence.

Effect of oxyprogesterone caproate, tamoxifen and their combination on the level of steroid hormone receptors in the tumor, and some parameters of the reproductive system in patients with endometrial cancer.

The results of preoperative use of oxyprogesterone caproate (OPC), Tamoxifen and their combination in 165 patients suffering from primary endometrial carcinoma are presented. It was shown that Tamoxifen was able to increase concentrations cytoplasmatic receptors to progesterone in the tumor. The incidence of specific hormonal pathomorphosis in the tissue of the tumor in patients who received a combination of OPC and Tamoxifen was significantly higher (80% of cases) as compared to the separate use of OPC (60%) or Tamoxifen (57%).

Study of sequences of DNA of the human papilloma virus genotypes 6 and 16 in patients with cancer of vulva and cervix uteri.

Puntaction hybridization method was used to determine the incidence of the human papilloma virus infection in cases with the squamous cell cancer of the vulva and cervix uteri. The presence of sequences of DNA of the HPV genotype and 16 was found in 74.2% of cases, which points to a suspicion for the involvement of the above viruses in etiology of cervix uteri cancer, as well as vulva cancer.

Treatment planning in vulvar cancer patients.

Peculiarities of metastatic spread, recurrences and treatment results were studied in 148 vulva cancer patients, indications to adequate treatment were specified with respect to age, local and regional tumour spread. Efforts to apply on a wider scale preventive and therapeutic removal of inguinofemoral lymph nodes, to make vulvectomy and lymphadenectomy more radical, employment of radiotherapy with fast electrons lead to a substantial improvement of prognosis.

Cervix uteri cancer and pregnancy.

It has been showed effectiveness of cytological screening among 4230 pregnant women for revealing early forms of the cervical cancer. It has been revealed that since the half of gravidity a prognosis of cervical cancer was getting worse. Variants for treatment of patients with combination gravidity and cervical carcinoma are regarded.

Can primary endometrial carcinoma stage I be cured without surgery and radiation therapy?

The data on 19 cases of primary endometrial carcinoma, stage I (mean age 28.0 years), cured by the administration of hydroxyprogesterone caproate without surgery and radiation therapy are presented. Clinical recovery in 15 cases was confirmed by repeated cytological and histological examinations of the endometrium. Hydroxyprogesterone caproate dose per course ranged within 25.0-83.0 g. In 4 patients with moderately differentiated cancer (G2), hormonal treatment was carried out in combination with chemotherapy. When tumor regression was confirmed histologically, steroid contraceptives were administered to induce an artificial menstrual cycle. At the closing stage of therapy clomiphene citrates were given in succession to restore the ovulatory cycle. Perspectives of administration of progestogens in young women with stage I endometrial carcinoma as a separate method of therapy are discussed.

Two pathogenetic types of endometrial carcinoma.

The author presents a hypothesis that the complex of endocrine and metabolic disturbances arising long before the development of endometrial carcinoma determines the biological peculiarities of the tumor, its clinical course, and the prognosis of the disease. On the basis of a prospective study of 366 patients with endometrial carcinoma, the author postulates that there are two different pathogenetic types of endometrial carcinoma. The first pathogenetic type of the disease arises in women with obesity, hyperlipidemia, and signs of hyperestrogenism: anovulatory uterine bleeding, infertility, late onset of the menopause, and hyperplasia of the stroma of the ovaries and endometrium. The second pathogenetic type of the disease arises in women who have no signs stated above or these signs are not clearly defined. The frequency of the first pathogenetic type in the studied group of women was 65%, whereas the frequency of the second type was 35%. The peculiarities outlined above which are characteristic of the first pathogenetic type of the disease determine the development of highly and moderately differentiated tumors (82.3% G1 and G2), superficial invasion of the myometrium (69.4%), high sensitivity to progestogens (80.2%), and favorable prognosis (85.6% 5-year survival rate). In patients who have the second pathogenetic type of endometrial cancer when endocrine and metabolic disturbances are absent or occult, poorly differentiated tumors arise (62.5% G3), a tendency to deep invasion of tumor into the myometrium is observed (65.7%); high frequency of metastatic spread into the pelvic lymph nodes (27.8%); decrease of sensitivity to progestogens (42.5%); and doubtful prognosis (58.8% 5-year survival rate) are noted.