Different Patterns of Disease Spread between Advanced-Stage Type I and II Epithelial Ovarian Cancer.

BACKGROUND AND AIMS: Two types of epithelial ovarian carcinoma (EOC) have been recently distinguished. Type I comprises low-grade serous, endometrioid and clear-cell tumors. High-grade endometrioid and serous tumors belong to type II. The aim of this study was to compare patterns of disease spread in advanced-stage type I and II EOCs at primary surgery. METHODS: Surgical and pathological data of 233 patients with advanced-stage EOCs were collected, 42 with type I and 191 with type II. The two groups were compared for tumor localization at primary surgery. Intraoperative mapping of ovarian cancer (IMO) was used to assess tumor dissemination. RESULTS: Tumor involvement was significantly higher in the type II group for the following: peritoneum (68.1 vs. 40.5%, p < 0.001), pouch of Douglas (60.2 vs. 40.5%, p = 0.06), vesicouterine ligament (40.8 vs. 19%, p = 0.027), diaphragm (45.0 vs. 11.9%, p < 0.001), serosa of liver (17.2 vs. 4.8%, p = 0.05), omentum (81.1 vs. 59.5%, p = 0.007), mesentery (42.9 vs. 16.7%, p = 0.005), pleural effusions (19.4 vs. 4.6%, p = 0.01) and ascites (60.7 vs. 21.4%, p < 0.001). IMO levels were different between the two groups (p = 0.001). CONCLUSIONS: This study provides clinical evidence in favor of the dualistic model of carcinogenesis, since types I and II are characterized by different findings at primary surgery.

Management of bilateral malignant ovarian germ cell tumors: a MITO-9 retrospective study.

OBJECTIVES: Bilaterality is rare in malignant ovarian germ cell tumors (MOGTs). The bilateral ovarian involvement represents a critical issue when diagnosed in young women desiring to preserve fertility. The aim of this study was to evaluate clinical characteristic and management of patients bilateral MOGTs. METHODS: Patients affected by bilateral MOGT and treated at MITO group centers were reviewed. RESULTS: In 145 patients with MOGTs, 5.5% were bilateral. Three patients were affected by dysgerminoma (associated with bilateral gonadoblastoma in 1), 2 by immature teratoma, 2 by mixed germ cell tumors, and 1 by embryonal carcinoma. International Federation of Gynecology and Obstetrics stage was 3 IB, 1 IC, 3 IIIC, and 1 IV. Three patients received radical surgery, and the patient with dysgerminoma associated with gonadoblastoma received bilateral adnexectomy. Four patients received fertility-sparing surgery; 2 patients received unilateral salpingo-oophorectomy and contralateral cystectomy; in 2 patients, the ovaries were completely transformed in neoplastic tissue; suspecting a contralateral dysgerminoma histology, a unilateral salpingo-oophorectomy and contralateral biopsy were performed, and the contralateral neoplastic ovary was left unresected. Six patients received adjuvant chemotherapy. Seven patients are disease free after a median follow-up of 54 months. The patient affected by embryonal carcinoma died of disease. Two patients resumed menstruation, and one had a pregnancy. A compromised ovarian function was found in 2 patients, and they were addressed to oocyte cryopreservation. CONCLUSIONS: Bilateral MOGTs have a good prognosis. In dysgerminoma histology, residual disease could be left to spare fertility. An oncological and reproductive function follow-up is recommended.

A multicentric trial (Olympia-MITO 13) on the accuracy of laparoscopy to assess peritoneal spread in ovarian cancer.

OBJECTIVE: The objective of the study was to prospectively evaluate the accuracy of laparoscopy performed in satellite centers (SCs) to describe intraabdominal diffusion of advanced ovarian cancer (AOC). STUDY DESIGN: Patients with a clinical/radiological suspicion of AOC were included in the protocol. SCs were selected among those surgeons, spending a short intensive training period at the coordinator center (CC) to learn the application of staging laparoscopy (S-LPS) in AOC. All women underwent S-LPS at the SCs, and the surgical procedure was recorded and blindly reviewed at the CC. Calculating specificity, positive and negative predictive values, and the accuracy for each parameter with respect to the CC assessed the diagnostic performance of S-LPS. The Cohen's kappa was used to test the interobserver agreement of each parameter. RESULTS: One hundred sixty-eight cases were considered eligible for the study. A per-protocol analysis was performed on 120 cases. The worst laparoscopic assessable feature was mesenteric retraction, whereas the remaining variables ranged from 99.2% (peritoneal carcinomatosis) to 90% (bowel infiltration). All but 1 SC (SC number 4) reached an accuracy rate of 80% or greater for both single parameters and overall score. The Cohen's kappa and the P value for overall predicitive index value were 0.685 and .01, respectively, but improved to 0.773 and .388 after removing the SC number 4 from the analysis. CONCLUSION: S-LPS allows an accurate and reliable assessment of intraperitoneal diffusion of disease in AOC patients in trained gynecological oncology centers.

Clear cell and papillary serous endometrial carcinomas: survival in a series of 128 cases.

PURPOSE: Clear cell (CC) and papillary serous carcinoma (PS) are histotypes at high risk of recurrence. We analyse patients' survival in a retrospective series of 128 CC and PS endometrial cancer cases. METHODS: All women with a histologically confirmed CC and PS endometrial cancer who underwent primary surgery in five institutions in Lombardy, Italy, were eligible for this study. A total of 77 (60.2 %) were PS endometrial cancer cases, 45 (35.2 %) CC cases and 6 (4.6 %) cases had mixed CC and PS histotype. RESULTS: 54 (42 %) cases were diagnosed at stage I, 10 (8 %) at stage II, 47 (37 %) at stage III and 17 (13 %) at stage IV. Recurrence was observed in 49 cases (38.3 %). The median time at recurrence was 12 months (interquartile range 7-18). The rate of recurrence was 20.3 % in cases at stage I-lI and 56.2 % in cases at stage III-IV (p < 0.0001). With regard to the site of recurrence 24 recurrences were in and 52 outside the pelvis. Finally, the rate of recurrence was 32.6 % (14 cases) in CC cases, 43.1 % (31 cases) in PS cases and 66.7 % (4 cases) in cases with mixed histotype. The 5-year progression-free survival was 59.5 % (67.4 % for CC cases, 55.1 % for PS and mixed cases). CONCLUSION: In this study including CC and PS endometrial cancers, the 5-year survival from surgery was 72.7 % and the 5-year progression-free survival was 59.5 %.

Uterine papillary serous, clear cell, and poorly differentiated endometrioid carcinomas: a comparative study.

INTRODUCTION: Uterine papillary serous and clear cell carcinomas (UPSCs/CCs) show a different spreading from that of poorly differentiated endometrioid carcinomas (PDECs) and are usually thought to be prognostically more aggressive than PDECs. On the contrary, it has been recently claimed that UPSC/CC and PDEC have a similar prognosis. In this retrospective study on 2 institutional databases, the surgical-pathological data and survival have been compared in patients with UPSC/CC and PDEC. METHODS: A total of 139 surgically staged consecutive patients, 63 with UPSC/CC (37 UPSC; 26 CC) and 76 with PDEC clinically limited to the uterine corpus, have been compared for nuclear ploidy, myometrial invasion, (occult) cervical extension, peritoneal, and lymph node metastasis. Prognostic factors have been correlated through multivariate analysis with survival (disease-specific [DSS] and disease-free [DFS]). RESULTS: Peritoneal metastases and aneuploidy were found to be the only parameters significantly different in the 2 groups: peritoneal metastases 28.6% in UPSC/CC (extrapelvic 19%) and 7.9% in PDEC (extrapelvic 2.6%) (P = 0.001), aneuploidy 48.6% in UPSC/CC and 30.6% in PDEC (P = 0.05). Five-year DSS was 57.9% versus 75.2% (P = 0.02), and DFS was 52.3% versus 71.4% (P = 0.04) for UPSC/CC and PDEC, respectively. All but cervical and lymph node involvement were significant predictors of survival. After multivariate analysis, histotype (DSS: hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.02-3.86; P = 0.04; DFS: HR, 1.94; 95% CI, 1.04-3.63; P = 0.04), stage (DSS: HR, 2.26; 95% CI, 1.10-4.65; P = 0.03; DFS: HR, 2.21; 95% CI, 1.12-4.38; P = 0.02), and myometrial invasion (DSS: HR, 2.86; 95% CI, 1.22-6.69; P = 0.01; DFS: HR, 3.96; 95% CI, 1.63-9.62; P = 0.002) were independent risk factors for survival. CONCLUSIONS: Uterine papillary serous and clear cell carcinomas spread to abdominal peritoneum more frequently than PDEC; multivariate analysis confirms UPSC/CC as an independent, unfavorable predictor of outcome.

Adjuvant treatment with concomitant radiotherapy and chemotherapy in high-risk endometrial cancer: a clinical experience.

OBJECTIVE: The concurrent use of radiotherapy (RT) and chemotherapy (CT) as adjuvant treatment after surgery in high-risk endometrial cancer has been generally considered cautiously. Recently some of us have reported preliminary data on the efficacy and tolerability of concomitant CT and RT. In this paper, we update our experience. METHODS: A total of 47 patients aged >18 years and <80 years with histological diagnosis of high-risk endometrial endometrioid carcinomas entered the study. Inclusion criteria were stages IC G3, IIB, IIIA (patients with positive washing without other unfavourable prognostic factors were omitted), IIIB and IIIC. The radiation plan consisted of a total dose of 50.4 Gy, given in five fractions per week (1.8 Gy: daily dose) for 6 weeks. Paclitaxel (P) at a dose of 60 mg/m(2) was infused intravenously in 250 mL of normal saline for 1 h once weekly during RT for 5 weeks. Three further cycles of Paclitaxel, at a dose of 80 mg/m(2), have been given weekly at the end of RT. RESULTS: There was no life-threatening toxicity. The overall 5-year relapse-free survival was 81.8% (95% CI, 65.2-90.9). The 5-year percent overall disease-specific survival was 88.4% (95% CI, 71.1-95.6). CONCLUSIONS: These results, based on a larger series, support our previous data: Paclitaxel plus RT may represent an effective and well-tolerated treatment in high-risk endometrial cancer patients.

Management of locally advanced cervical cancer in pregnancy: a case report.

BACKGROUND: Carcinoma of the cervix is the most common malignancy associated with pregnancy. In the first and second trimesters patients should receive the same treatment as is used in nonpregnant women and termination is advised. In selected cases neoadjuvant chemotherapy (NACT) could be proposed but only a few cases have been reported. CASE: A 27-year-old woman, gravida 1 para 0, at 15 weeks' gestation, was diagnosed with FIGO stage IB2 squamous cervical cancer. After refusing to terminate pregnancy, she was treated with neoadjuvant chemotherapy (cisplatin) starting at 18 weeks. A cesarean section with radical surgery was performed at 32 weeks and a healthy baby delivered. Four weeks later the patient started chemoradiation therapy. She relapsed 1 year after surgery and died when her child was 2 years old. CONCLUSION: NACT followed by radical surgery was an unsuccessful treatment in our patient; platinum-based chemotherapy was harmless to the child up to the last follow-up.

Paclitaxel and concomitant radiotherapy in high-risk endometrial cancer patients: preliminary findings.

BACKGROUND: There is still much debate about the best adjuvant therapy after surgery for endometrial cancer (EC) and there are no current guidelines. Radiotherapy (RT) alone does not seem to improve overall survival. We investigated whether concomitant Paclitaxel (P) and RT gave better clinical results. METHODS: Twenty-three patients with high-risk EC (stage IIB, IIIA, IIIC or IC G3 without lymphadenectomy or with aneuploid tumor) underwent primary surgery and were then referred for adjuvant therapy. P was given at a dose of 60 mg/m2 once weekly for five weeks during RT, which consisted of a total radiation dose of 50.4 Gy. Three further weekly cycles of P at a dose of 80 mg/m2 were given at the end of RT. Overall survival and disease-free survival were calculated from the time of surgery. Patterns of failure were recorded by the sites of failure. RESULTS: A total of 157 cycles of P were administered both during radiotherapy and consolidation chemotherapy. Relapses occurred in five patients (21.7%). Median time to recurrence was 18.6 months (range 3-28). Survival rate for all the patients was 78.2%. Overall survival for the patients who completed chemo-radiation was of 81%. In this group median time to recurrence was 19.2 months (range 3-28). All recurrences were outside the radiation field. Mortality rate was 14.2%. CONCLUSION: This small series demonstrates pelvic radiotherapy in combination with weakly P followed by three consolidation chemotherapy cycles as an effective combined approach in high risk endometrial carcinoma patients.

Tension-free vaginal tape (TVT) and intravaginal slingplasty (IVS) for stress urinary incontinence: a multicenter randomized trial.

OBJECTIVE: This study was undertaken to compare the efficacy and morbidity of 2 minimally invasive procedures for stress urinary incontinence. STUDY DESIGN: This was a prospective randomized multicenter trial; 190 women with primary urodynamic stress incontinence were randomly assigned to tension-free vaginal tape (TVT) (n = 95) or intravaginal slingplasty (IVS) (n = 95). The primary and secondary outcome measures were rates of success and complications. SPSS software was used for data analysis. RESULTS: At 2 years 92 and 87 patients were available in the TVT and IVS group for outcomes analysis. Subjectively, 80 (87%) and 68 (78%) women were cured, respectively. Objectively, a 1-hour pad test was negative in 78 (85%) and 63 (72%) patients. Eight of the patients assigned to IVS (9%) had vaginal erosion/infection, compared with none in the TVT group (P < .01). CONCLUSION: Both procedures were effective for stress incontinence, but 9% of women treated with the IVS required removal of the tape for erosions.

Investigational therapies currently in Phase II clinical trials for the treatment of pelvic serous carcinomas.

INTRODUCTION: Pelvic serous carcinomas (PSCs) are a controversial entity, which mostly comprise fallopian tube carcinoma (FTC), primary peritoneal carcinoma (PPC) and serous ovarian carcinoma (OC). Despite incremental attention towards understanding pelvic serous carcinogenesis, the gold standard treatment and survival rates have not substantially changed in these last decades. AREAS COVERED: This review summarizes and gives a critical overview of the ongoing Phase II trials investigating therapies for PSC. EXPERT OPINION: Several novel molecules have been developed and are currently under investigation for the treatment of PSC, including FTC, PPC and serous OC. The trend of novel targeted agents is one towards individualized, tailored therapy, based on the molecular and biological differences that characterize tumors that seem similar based solely on histological analysis. The task of developing new molecules is particularly difficult for PSC, given the recurrent development of new patterns of drug resistance. However, even if current research is focused towards identifying the best treatments for each woman with a molecularly defined disease, a deeper knowledge of the molecular biology and genetics underlying FTC and its relation as a precursor of PSC is needed.

Surgical treatment of elderly patients with endometrial cancer (≥ 65 years).

OBJECTIVES: To analyze operability, short-term morbidity and mortality in women aged 65 and older with endometrial cancer. MATERIALS AND METHODS: The study cohort consisted of 124 elderly patients, aged 65 and older, with endometrioid endometrial cancer. Patients' clinical data included age at diagnosis, body mass index, ASA (American Society of Anesthesiologists) status and comorbidities, surgical procedures, FIGO (International Federation of Gynecology and Obstetrics) stage, histologic type, occurrence of operative and postoperative complications, and long-term disease-specific survival. Patients were divided into two groups according to age: those < 75 years and those ≥ 75 years. The analysis was repeated for patients older than 80 years who represent the category most at risk for perioperative morbidities. RESULTS: All patients were referred to primary surgery (abdominal versus vaginal) with the exception of 3 patients. Factors affecting significantly the choice of intervention were age, body mass index, and the presence of comorbidities. No women died during the perioperative period. The rate of perioperative complications was significantly higher for the older group. In a logistic regression model, aged ≥ 75 years (but not aged ≥ 80 years), chronic lung disease and performing lymphadenectomy correlated with a higher probability of perioperative morbidities. Long-term disease-specific survival was significantly shorter only for women aged ≥ 80. CONCLUSION: Geriatric patients should not be denied surgical treatment because of perceived risks associated with chronologic age, since the removal of the uterus confers a survival benefit.

Surgery in advanced borderline tumors.

Our retrospective study evaluates the role of conservative surgery, performed in 10 of 22 patients affected by advanced stage serous borderline ovarian tumor. Although patients who underwent conservative surgery had a higher recurrence rate (60% after conservative surgery and 8% after radical surgery), all patients are alive without evidence of disease.

High-grade endometrial cancer: value of [(18)F]FDG PET/CT in preoperative staging.

OBJECTIVE: The purpose of this study was to assess the value of 2-[F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([F]FDG PET/CT) in the primary staging of high-risk endometrial cancer patients. METHODS: This retrospective study was conducted on 32 consecutive patients with histological diagnosis of primary high-risk endometrial cancer, who underwent PET/CT with [F]FDG in addition to conventional clinical and instrumental staging procedures. After surgery, [F]FDG PET/CT findings were correlated with pathological findings on a patient-by-patient basis. The diagnostic accuracy of [F]FDG PET/CT for primary cancer detection, lymph nodal involvement and distant metastases was assessed. RESULTS: [F]FDG PET/CT could correctly detect primary tumor in 29 of the 32 high-risk patients, with a sensitivity of 90.6%. The overall [F]FDG PET/CT patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 57.1, 100.0, 100.0, 86.4, and 88.5%, respectively, for revealing lymph nodal neoplastic involvement, and 100.0, 96.0, 87.5, 100.0, 96.9%, respectively, for detecting distant metastases. In particular, while the suspicion of distant metastases was documented by conventional imaging in only two patients, [F]FDG PET/CT correctly identified metastatic lesions in seven patients (21.9% of cases). CONCLUSION: The major benefit provided in high-grade tumor patients by the use of [F]FDG PET/CT in the primary staging of endometrial cancer is its ability to accurately detect distant metastases in the abdomen and extra-abdominal regions. [F]FDG PET/CT adds relevant information that may influence patient management.

Integrated FDG PET/CT in patients with persistent ovarian cancer: correlation with histologic findings.

PURPOSE: To prospectively evaluate the accuracy of integrated positron emission tomography (PET) and computed tomography (CT) for depiction of persistent ovarian carcinoma after first-line treatment, with use of histologic findings as the reference standard. MATERIALS AND METHODS: Thirty-one women (mean age, 55.9 years) with ovarian carcinoma treated with primary cytoreductive surgery and followed up with platinum regimen chemotherapy were included. All 31 patients were scheduled for surgical second-look. Before surgical second-look, all patients underwent fluorodeoxyglucose (FDG) PET/CT. At PET/CT, three main categories of persistent disease were considered for data analysis: lymph nodal lesion, peritoneal lesion, and pelvic lesion. In all patients, imaging findings were compared with results of histologic examination after surgical second-look to determine the diagnostic accuracy of PET/CT in the evaluation of disease status. The kappa statistic (Cohen kappa) was used for statistical analysis. RESULTS: Seventeen (55%) of 31 patients had persistent tumor at histologic analysis after surgical second-look, and fourteen (45%) had no histologically proved tumor. The total number of lesions that was positive for tumor cells at histologic analysis was 41 (lymph nodes, n = 16; peritoneal lesions, n = 21; pelvic lesions, n = 4); maximum diameter of these lesions was 0.3-3.2 cm (mean, 1.7 cm). A correlation was found between PET/CT and histologic analysis (kappa = 0.48). The overall lesion-based sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT were 78%, 75%, 77%, 89% and 57%, respectively. In the detection of a tumor, a size threshold could be set at 0.5 cm, as this was the largest diameter of a lesion missed at PET/CT. CONCLUSION: Integrated PET/CT depicts persistent ovarian carcinoma with a high positive predictive value.