ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease.

The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.

Maspin expression in endometrial hyperplasia and carcinoma, and its relation with angiogenesis.

AIM: The purpose of this study was to evaluate the maspin expression in endometrial hyperplasia and cancer, and also to investigate its relation with angiogenesis. MATERIALS AND METHODS: A total of 19 women with complex atypical hyperplasia, 44 patients with simple hyperplasia without atypia, and 67 patients with endometrial carcinoma were included. Maspin expression was assessed by immunohistochemistry (IHC), and tested for possible significant relation with age, FIGO stage, histologic type, grade, depth of myometrial invasion (MI), lymphovascular space involvement (LVSI), lymph node metastasis, and overall survival (OS). Angiogenesis was determined by vascular endothelial growth factor (VEGF) staining. RESULTS: Maspin expression was detected in only three patients with endometrial hyperplasia (5%). In patients with endometrial cancer, cytoplasmic and nuclear maspin expressions were detected in 36 (53.7%) and 18 (26.9%) patients, respectively. No significant relation was noted between staining localizations and prognostic variables. The five-year OS rate for patients with cytoplasmic staining was 91%, compared to 87% for patients without staining (p = 0.31). These values for nuclear expression were 100% and 87%, respectively (p = 0.16). The cytoplasmic and nuclear maspin expressions were found to be significantly correlated with VEGF (r = 0.278, p = 0.02 and r = 0.295, p = 0.01, respectively). DISCUSSION: This is the first study to demonstrate the relation between maspin expression and angiogenesis in endometrial cancer. Although no survival difference was noted for cytoplasmic or nuclear maspin expressions, a tendency was detected for nuclear staining. Further series will clarify the exact prognostic role of maspin expression in gynecological malignancies including endometrial cancer.

The role of frozen section evaluation in the diagnosis of adnexal mass.

The purpose of this study was to evaluate the accuracy of frozen section diagnosis in patients who were subjected to the exploratory laparotomy for pelvic mass. Overall, 207 patients were included in this study and the mean age of the patients was 50.9 +/- 14.9 years (range, 18-84 years). Of these patients, 98 (47%) had benign, 16 (8%) had borderline, and 93 (45%) had malignant histologies at permanent section. The diagnosis at frozen section was deferred for three patients (1.4%) and these patients were excluded from the further analyses. The overall discordance rate was 5.3%. To calculate the sensitivity and specificity values, 2 x 2 contingency tables were constructed in two ways. In the first calculation, borderline histology was considered malignant, and the sensitivity and specificity rates were 97% and 92%, respectively. In the second analysis, it was accepted as benign, and these values were 100% and 98%, respectively. To determine the possible factors related with discordant diagnoses, age, menopausal status, tumoral size, laterality of tumors, and histologic diagnoses were analyzed. Significant association was noted for size and borderline and mucinous histologies. In patients with borderline histology, the discordance rate was 40%. This value for the remaining patients was 3.2% (P < 0.001). The rate of misdiagnosis was 17.4% for mucinous tumors, whereas it was 4.8% for the remaining epithelial tumors (P = 0.03). Frozen section evaluation revealed high sensitivity and specificity values in this study. To increase the accuracy of diagnosis, further diagnostic markers are needed especially for patients with large lesions, borderline tumors, and mucinous histologies.

Topotecan as a second-line therapy in patients with ovarian and primary peritoneal cancer: initial response and long-term follow-up.

The purpose of this study was to evaluate the role of topotecan at a dose of 5-day standard 1.5 mg/m2/day in patients with relapsed ovarian cancer. Two different groups of patients were included. In group 1, 23 patients who had bidemensionally measurable disease were examined, and in group 2, 11 patients were given topotecan after positive second-look laparotomy (SLL) were analyzed. Total number of cycles was 190 with a median value of six cycles. In group 1, three (13%) patients had complete response (CR) and seven (30%) had partial response (PR) with a total response rate of 43%. Six patients (27%) had stable disease (SD), and seven (30%) had progressive disease (PD). Median survival durations for patients with CR, PR, SD, and PD were 35, 14, 15, and two months, respectively. In group 2, two patients had PD during treatment. The remaining nine patients had no measurable disase or marker relapse at the end of treatment period. Median survival duration was 27 months. In conclusion, topotecan had significant antitumor activity as a second-line therapy in relapsed ovarian cancer patients with measurable disease. In a subgroup of patients with positive second-look laparotomy topotecan was also associated with long median survival duration.

Assessment of human papilloma viral load of archival cervical intraepithelial neoplasia by real-time polymerase chain reaction in a Turkish population.

The purpose of this study was to determine the existence, and viral load of human papilloma virus (HPV) subtypes 16 and 18 in paraffinized cervical intraepithelial neoplasia (CIN) samples by real-time polymerase chain reaction (RT-PCR). Overall 94 women were included. Of these patients 47 (50%) had CIN I, 27 (28.8%) had CIN II, and 20 (21.2%) had CIN III. HPV positivity for these three groups were 4.2%, 14.8% and 45%, respectively. HPV positivity in CIN III patients was significantly higher than CIN I (OR = 18.41, 95% CI 3.00-145.73; p < 0.001), and CIN II patients (OR = 4.70, 95% CI 1.00-23.76; p = 0.05). The difference between CIN I and II was not significant (p = 0.18). Viral loads were 10(2), and 10(4) copy/ml for two CIN I patients; 10(2), 10(3), and 10(5) for three CIN II patients; and 10(2), 10(3), 10(4), 10(4), 10(5), 10(5), and 10(6) copy/ml for eight patients with CIN III. Viral load of the remaining one patient could not be assessed. No significant variance was noted among the groups with respect to viral load (p = 0.73). RT-PCR had important advantages of detecting, typing, and quantifying at the same time. Although HPV positivity was increased significantly by the degree of lesions, this relation was not observed for viral load.

Surgical stage III endometrial cancer: analysis of treatment outcomes, prognostic factors and failure patterns.

OBJECTIVE: The purpose of this study was to evaluate the survival estimates of stage III endometrial cancer patients, and also to detect the prognostic factors and failure patterns. MATERIALS AND METHODS: Sixty-eight surgical Stage III endometrial cancer patients treated at Hacettepe University Hospital were included. All patients underwent surgical staging procedures consisting of peritoneal cytology, infracolic omentectomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy and complete pelvic-paraaortic lymphadenectomy. By surgical staging 26 (38%) patients had Stage IIIA and 42 (62%) patients had Stage IIIC disease. The mean resected lymph node number was 26 (median, 25; range, 15-58). RESULTS: The median age was 60 years (range, 38-77), and the median follow-up period was 62 months (range, 36-90 months). The 5-year disease free survival rate was 58% and the 5-year overall survival rate was 64%. These figures for Stage IIIA were 60% and 68%, respectively; and for Stage IIIC they were 57% and 62%, respectively. No significant survival difference was detected between Stage IIIA and IIIC (p = 0.60 for disease-free survival and p = 0.48 for overall survival). High grade and positive peritoneal cytology predicted poor survival in both univariate (p = 0.004 and p = 0.006, respectively) and multivariate (p = 0.05 and p = 0.04, respectively) analysis. Twenty-eight patients (41%) had recurrence with a median time of 23 months (range, 10-54 months). Nine patients (13%) had only local, 13 patients (19%) had only distant and six patients (9%) had both local and distant relapse. CONCLUSION: Surgical staging is important in the management of Stage III endometrial cancer, and the main problem is still distant failure. In multivariate analysis high grade and positive peritoneal cytology predicted poor survival significantly.

Oncologic and reproductive outcome after fertility-saving surgery in ovarian cancer.

The rate of ovarian tumour diagnosis in reproductive age woman has increased parallel to the improvements in diagnostic methods and regular gynaecological visits. Because of this organ saving surgical procedures for the preservation of reproductive and endocrine functions have gained more interest. Conservative surgical approaches for ovarian tumours after surgical staging include cystectomy, unilateral salpingo-oophorectomy and unilateral salpingo-oophorectomy plus contralateral cystectomy. Ovarian tumours diagnosed in young ages tend to be low-stage low-grade malignancies. This not only enables but also necessitates preserving the fertility of women who have not completed their family. In invasive ovarian cancer, fertility saving surgery is confined to early-stage and low-grade disease. But, it also had been reported in advanced stages (up to Stage IIIc). Candidates for those procedures were selected according to the FIGO stage, grade, ploidy state, histological subtypes and patients' desire. Adjuvant chemotherapy is necessary for high-risk patients. The rate of recurrence following conservative and radical surgical procedures in low-stage and low-grade tumours are 9% and 11.6%, respectively; and disease-free and overall survival rates do not differ significantly. Prognosis of borderline ovarian tumours is excellent. Five and 20-year survival rates are 95% and 80%, respectively. Management of borderline tumours has evolved significantly in the last few decades. In contrast to invasive ovarian cancer, borderline tumours can be operated on conservatively at all stages. Chemotherapy is rarely prescribed even in advanced stages. Eighty percent of malignant germ cell tumours are diagnosed less than 30 years of age, and 70-75% of patients have Stage I disease. Conservative surgery is generally used in malignant germ cell tumours even in advanced stages. The relation between ovulation induction and tumour recurrence is not consistent in the literature. Spontaneous pregnancy rates following fertility saving surgery has been reported as 60-88%. Because of this over-treatment of these patients for fertility should be avoided. Briefly, fertility saving surgery can be performed safely in germ cell, borderline and early stage epithelial ovarian tumours in selected cases. Any increment in the rate of tumour recurrence following ovulation induction has not yet been demonstrated. Menstrual irregularities caused by chemotherapy are transient. The congenital malformation rate of ovarian cancer patients is slightly higher than that of the normal population, but no significant difference has been observed between patients who received or did not receive chemotherapy.

Ovarian metastasis of primary biliary and gallbladder carcinomas.

The ovary is a frequent site of metastasis from a wide variety of malignant neoplasias, with the majority originating in the GI tract. The best known tumor of this type is signet ring cell adenocarcinoma (Krukenberg tumor). The gallbladder and bile ducts are rare sources of these metastases. We are reporting two such cases in which the patients presented with no hepatic symptoms and vague gastrointestinal complaints. The gallbladder and bile duct carcinomas were incidental findings during exploratory laparatomy for an ovarian mass.

An extraordinary case of four primary tumors in the same patient, involving the uterine cervix, lung, skin, and rectum.

Four primary cancers in one patient are fairly rare. Here we present a case of four primary tumors in such a patient. These cancers were cervical carcinoma and lung carcinoma, which occurred synchronously, and basal cell carcinoma of the skin and rectal carcinoma which occurred metachronously. A successful resection of two synchronous and two metachronous cancers, which has never previously been reported in this specific combination, is described.

Ascites and epithelial ovarian cancers: a reappraisal with respect to different aspects.

Ascites is a common finding in patients with epithelial ovarian cancer (EOC). Clinico-pathologic correlations with respect to the presence of ascites, positive cytology and prognostic role of ascites, and the impact of ascitic volumes were not previously studied extensively. A total of 372 patients with EOC were retrospectively evaluated with respect to presence and amount of ascites, cytologic findings, and survival. Two groups were compared by using Chi-square, Student's t and Mann-Whitney U, binary logistic regression, Kaplan Meier and Cox-regression analysis tests, where appropriate. Omental metastasis (P < 0.001; OR: 3.21, 95% CI = 1.945-5.297) and mean number of metastatic lymph nodes (P= 0.008; OR: 1.063, 95% CI = 1.016-1.112) were significantly related with presence of ascites. Evaluation of ascitic volume at different thresholds revealed lymphatic-omental metastasis, and also the disease stage to be significantly different among patient groups at lower threshold values and the positive cytology and high-grade diseases at higher threshold values. In conclusion, presence of ascites correlates with both the intraperitoneal and also the retroperitoneal tumor spread. Amount of ascites has different correlations with the clinico-pathologic factors depending on the thresholds chosen. At lower volumes, lymphatic and omental metastasis seems to correlate with the development of ascites. Once ascites develops, tumor grade seems to be important for larger ascites volumes. Neither the presence of ascites or its volume nor the cytologic positivity was an independent predictor of survival.

Does immediate hormone replacement therapy affect the oncologic outcome in endometrial cancer survivors?

The purpose of this study was to evaluate the effect of immediate hormone replacement therapy (HRT) on oncologic outcome of patients with endometrial cancer. The patients were recruited prospectively after extensive discussion of risks and benefits of HRT. Continuous daily regimen of 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate was initiated 4-8 weeks after surgery at first postoperative visit. The patients who had the same characteristics with the HRT group were assigned as a control group. Overall, 50 patients received HRT. There was no significant difference with respect to prognosticators between the HRT users and the control group. Seven patients (14%) stopped the use of HRT. Only two patients stopped the therapy before 24 months, and all the remaining patients used HRT for at least 24 months, with a mean value of 49.1 months. Neither the patients who used HRT nor the ones who left the therapy had recurrence at the time of writing of this article. This prospective case-control study showed that immediate postoperative use of HRT did not increase the recurrence or death rates in endometrial cancer survivors.