[Update on current care guidelines: ovarian cancer]. / Munasarjasyöpä.

Ovarian cancer is the most lethal gynaecological cancer. It appears that seemingly ovarian or primary peritoneal carcinomas, in fact, originate from fimbriae. BRCA1/2 mutation carriers are recommended for the removal of ovaries and fimbriae, to reduce the risk of cancer. Treatment of epithelial ovarian cancer is based on the combination of surgery and chemotherapy. The residual tumour volume at the primary operation is the most important predictive factor of survival. The best response at the primary treatment is observed with combination chemotherapy with taxane and platinum. Adding bevacitzumab to first line chemotherapy may improve survival.

The effect of hospital operative volume, residual tumor and first-line chemotherapy on survival of ovarian cancer - a prospective nation-wide study in Finland.

OBJECTIVE: Our recent prospective, nation-wide study indicated better surgical outcome in ovarian cancer patients operated at university hospitals compared to other hospitals. Here we report how this is reflected in 5-year cancer-specific survival (CSS). METHODS: Detailed 5-year follow-up data were obtained on 275 patients by using a special questionnaire, and the data were verified from the Finnish Cancer Registry data. The hospitals were categorized to university and other hospitals and by the number of operations performed in 1999 (<10, 10-20, or >20 operations). Data were analyzed using the Cox's proportional hazards regression analysis. RESULTS: The study population covered 90% of the epithelial ovarian cancer patients operated in 1999, in Finland. Eighty-two percent of the patients received platinum-based chemotherapy. The percentage of patients treated with a platinum-taxane combination was higher in university hospitals (63% vs. 49%, P=0.037). The 5-year CSS was 56% and the median disease-free survival (DFS) was 33 months. In multivariate analysis prognostic factors for CSS were stage (P=0.0027), residual tumor (P=0.0001), and primary chemotherapy (P<0.0001). Hospital operative volume was associated with residual tumor (P=0.027). When hospital operative volume increased with ten patients per year, the odds ratio for no residual disease was 1.203 (95% CI 1.022-1.417). CONCLUSION: FIGO stage, residual tumor, and primary chemotherapy are significant prognostic factors for ovarian cancer. Hospital volume is associated with residual tumor. The results favor performance of ovarian cancer surgery in hospitals with higher operative volumes.

Surgically staged high-risk endometrial cancer: randomized study of adjuvant radiotherapy alone vs. sequential chemo-radiotherapy.

OBJECTIVE: Our purpose was to establish whether platinum-based chemotherapy combined with standard surgery and radiotherapy will improve overall and disease-free survival and lower the recurrence rate in patients with high-risk endometrial cancer. STUDY DESIGN: A total of 156 patients with Stage IA-B Grade 3 (n=28), or Stage IC-IIIA Grade 1-3 (n=128) were postoperatively randomized to receive radiotherapy (56 Gy) only (Group A, n=72) or radiotherapy combined with three courses of cisplatin (50 mg/m(2)), epirubicin (60 mg/m(2)) and cyclophosphamide (500 mg/m(2)) (Group B, n=84). RESULTS: The disease-specific overall five-year survival was in Group A 84.7% vs. 82.1% in Group B (p=0.148). The median disease-free survival in A was 18 (range 9-36) months and 25 (range 12-49) months in B (p=0.134), respectively. During a five-year follow-up 32 patients relapsed. Of the recurrences 5 were local and 20 distant, while 7 were combined. As calculated from the operation, the median time to recurrence was 15 (range 6-37) months in Group A, and 20 (range 8-60) months in Group B, respectively (p=0.170). Twenty-six patients died of the disease during the five-year follow-up, 11 in A and 15 in B. The patients succumbing in A lived a median 23 (range 15-44) months as compared to 37 (range 13-50) months in B (p=0.148). Chemotherapy was associated with an acceptable rate of acute toxicity. Less than 8% of the patients complained of Grade 3/4 nausea. The rate of Grade 3/4 leucopenia was at the highest at 16.6% during the third cycle but only 6.2% of the patients had Grade 3 infection. A total of 10 patients developed intestinal complications demanding surgery, 2 in Group A (2.7%) and 8 (9.5%) in Group B, respectively. CONCLUSION: Adjuvant chemotherapy with cisplatin, epirubicin and cyclophosphamide failed to improve overall survival or lower the recurrence rate in patients operated on and radiated for high-risk endometrial carcinoma. Chemotherapy was associated with a low rate of acute toxicity but appeared to increase the risk of bowel complications.

Surgical treatment of ovarian cancer in different hospital categories--a prospective nation-wide study in Finland.

This prospective nation-wide study was performed to evaluate the effect of hospital category and subspeciality training on surgical treatment of ovarian cancer. Data were obtained from a questionnaire filled in by the operating unit, and from the surgical and histopathology reports. The survey included 307 patients. Half of them were operated in the university hospitals where gynaecologic oncologists performed 72% of the operations. This was the case in only 4% and 19% in the central and district hospitals, respectively. In university hospitals, pelvic lymphadenectomy was performed in 88%, and para-aortic lymphadenectomy in 73%, of the patients with stage I disease. The corresponding figures ranged from 11% to 21% in central and district hospitals. For stage III patients operated by gynaecologic oncologists, the estimated odds ratio for no macroscopic tumour was 3.0 times higher (95% CI 1.2-7.5) than for those operated by general gynaecologists. These results favour centralisation of surgical treatment of ovarian cancer.

A randomised phase III study comparing high-dose chemotherapy to conventionally dosed chemotherapy for stage III ovarian cancer: the Finnish Ovarian Cancer (FINOVA) study.

Women with stage III ovarian cancer and with < or = 2 cm residual tumour were randomly assigned to receive either conventionally dosed chemotherapy (group A) or HDCT (group B). Patients allocated to group A received 6 cycles of paclitaxel (T) 135 mg/m2 and cisplatin (P) 75 mg/m2 every 3 weeks, and those allocated to HDCT received 3 TP cycles followed by peripheral blood stem cell mobilisation with cyclophosphamide (C) 3000 mg/m2 and T 175 mg/m2, and subsequently HDCT with carboplatin 1500 mg/m2, C 120 mg/kg, and mitoxantrone 75 mg/m2. The trial was closed early after 42 patients were entered due to slow accrual. The median follow-up time of patients who were alive was 81 months. The median progression-free survival time was 15.9 and 16.6 months (hazard ratio, HR 0.83; 95% CI 0.41-1.69, P = 0.61) and the median overall survival time was 43.7 and 64.3 months (HR, 0.74; 95% CI 0.34-1.61, P = 0.44) in groups A and B, respectively. Although one patient died of HDCT-related toxicity, the regimen was otherwise relatively well tolerated. We conclude that the HDCT regimen used was feasible, but did not result in significantly improved survival in this prematurely closed trial. A clinically important survival benefit cannot be excluded due to the small sample size.

Surgical staging, treatment, and follow-up of borderline tumors in different hospital categories: a prospective nationwide survey in Finland.

BACKGROUND: Surgical treatment and staging of ovarian borderline tumors have been reported to be often suboptimal and differ considerably. We evaluated the extent of surgical treatment of these tumors in different hospital categories. MATERIAL AND METHODS: A prospective survey performed in 1999 included 65 patients operated on for borderline ovarian tumors and covered 78% of such patients reported to the Finnish Cancer Registry. Detailed information of demographic data and surgical treatment was reported by the responsible physicians using a special questionnaire after confirmation of histopathology. RESULTS: Fifty-eight patients (89%) had stage I tumor, only two patients (3%) had stage II disease and five patients (8%) had stage III disease with peritoneal implants. The majority of the patients underwent bilateral salpingo-oophorectomy (66%) and hysterectomy (58%). Unilateral salpingo-oophorectomy was performed for 21 (32%) and omentectomy for 22 (34%) patients. Ten out of the 16 women under 40 years of age had fertility-sparing surgery. Peritoneal biopsies were taken in 16 (25%) women and lymphadenectomy was performed for 9 (14%) patients with clinical suspicion of invasive ovarian carcinoma. Frozen section was taken in half of the patients and the histology remained the same in 72% of the final pathology reports. No clear differences of the extent of surgical treatment were detected between different hospital categories. Overall cumulative 5-year relative survival rate was 96%. CONCLUSIONS: Bilateral salpingo-oophorectomy and hysterectomy was performed for the majority of patients with borderline ovarian tumor. More attention should be paid to adequate staging of borderline tumors in all hospital categories.

Sentinel node and vulvar cancer: a series of 47 patients.

BACKGROUND: There is growing interest to apply the sentinel node technique in the treatment of vulvar cancer. METHODS: All charts of the patients operated on for vulvar cancer at Tampere University Hospital from January 1, 2001 through June 30, 2005 were retrospectively reviewed. Demographic, clinical, and histopathological information was collected from each patient. The sentinel lymph node mapping was done intraoperatively either with a combination of the radioisotope and dye techniques (40 patients) or with the dye technique alone (7 patients). The sentinel lymph node was dissected separately for histopathological evaluation, and then a routine inguinal lymphadenectomy was performed. RESULTS: The final FIGO surgical Stage distribution was: Stage I, 11 (23%); Stage II, 14 (30%); Stage III, 21 (45%); and Stage IV, 1 (2%). Sentinel lymph node was identified in 46 (98%) women with either one or both of the methods. In Stage I-II, the sentinel lymph node identification rate was 25/25 (100%) with the combined method. The only patient with unidentified sentinel lymph node had lymphatic spread beyond inguinal area or Stage IV disease. Eighteen of the sentinel lymph nodes (39%) were positive for tumor cells, and in 5 cases additional metastatic nodes were found. One patient with macroscopically enlarged metastatic inguinal nodes and Stage III disease had a negative sentinel lymph node. In the 25 patients with Stage I-II disease, the false-negative rate of the sentinel lymph node method was 0/4, giving a negative predictive value of 1.00. CONCLUSIONS: A sentinel node identification rate of 98% with a false-negative rate of 0% in the patients with Stage I-II disease is an encouraging finding.

Sequential gemcitabine-carboplatin followed by paclitaxel-carboplatin in the first-line treatment of advanced ovarian cancer: A phase II study.

OBJECTIVE: To determine the feasibility and efficacy of sequential gemcitabine-carboplatin followed by paclitaxel-carboplatin in the first-line treatment of advanced epithelial ovarian cancer, with the response rate as the primary endpoint. METHODS: After primary laparotomy, 56 patients with FIGO Stages III-IV disease were given 4 cycles of gemcitabine 1000 mg/m2 d1,8 and carboplatin AUC5 (44 patients) or AUC6 (12 patients) d1 q3wk followed by 4 cycles of paclitaxel 175 mg/m2 d1 and carboplatin AUC5/6 q3wk. Of the tumors, 43 were serous, 6 clear cell, 4 endometrioid, and 3 anaplastic type. Thirty-seven (66.1%) of the patients were suboptimally debulked. RESULTS: Forty-seven patients were evaluable for response by CA-125 criteria, and 46 (98%) responded. Thirty patients (after gemcitabine-carboplatin) and 24 (after paclitaxel-carboplatin) were evaluable for response by CT (RECIST criteria), respectively. After the four gemcitabine-carboplatin cycles, the objective response rate was 83% (6 CR, 19 PR). Following completion of the whole sequential regimen, 7 patients showed a CR and 15 a PR, respectively, giving a response rate of 92%. The median progression-free survival was 12.8 months after a median follow-up of 19 months (range 7-35 months). The median overall survival has not been reached yet. The main toxicity was neutropenia as 139/221 (62.9%) of the gemcitabine-carboplatin cycles and 92/181 (50.8%) of the paclitaxel-carboplatin cycles, respectively, were associated with Grades 3-4 neutropenia. Neutropenia was reported as a serious adverse event in 5.7% of the cycles, and G-CSF support was needed in 18.4% of the cycles. Only the gemcitabine-carboplatin cycles were associated with a marked thrombocytopenia (32.1% Grades 3-4). Of the other side effects, marked allergy occurred in 14/52 (27%) exposed to paclitaxel. A total of 14 patients discontinued the treatment prematurely: 3 due to lack of efficacy, 1 due to protocol violation, and 10 due to toxicity (4 allergic reactions to paclitaxel, 3 complicated neutropenias, 1 fever, and 2 unspecified toxicities). The mean relative dose intensities were: gemcitabine 84.0%, paclitaxel 85.4%, and carboplatin 96.5%. Of the gemcitabine-carboplatin cycles and paclitaxel-carboplatin cycles, 32% and 38% were delayed, respectively. Gemcitabine d8 dose had to be omitted in 8% of the cycles. CONCLUSION: The sequential regimen of gemcitabine-carboplatin followed by paclitaxel-carboplatin is feasible in chemotherapy-naive ovarian cancer. Although its use is associated with a marked neutropenia, the neutropenia is manageable.

Clinical outcome and complications of laparoscopic surgery compared with traditional surgery in women with endometrial cancer.

INTRODUCTION: The purpose of this study was to evaluate the feasibility, clinical outcome and complications of laparoscopic surgery in women with endometrial cancer and to compare surgical outcome and postoperative early and late complications with results of traditional laparotomy. METHODS: Forty women with endometrial cancer underwent laparoscopic hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Each patient operated by laparoscopy was matched by age, preoperative clinical stage and histology of the endometrial cancer with a patient treated by the same operation but using traditional laparotomy. Half of these patients underwent total pelvic lymphadenectomy and half had pelvic lymph node sampling. The groups were compared in clinical characteristics, surgical outcomes, recoveries and early and late postoperative complications. RESULTS: The patients in the laparoscopy group had less blood loss, more lymph nodes removed, shorter hospital stay but longer operation time than those treated by laparotomy. Only one (2.5%) laparoscopy was converted to laparotomy due to pelvic adhesions. There were no intraoperative complications in either group. Postoperative complications were more common (55.0%) in the laparotomy than in the laparoscopy group (37.5%). Only one major complication (2.5%) occurred among patients undergoing laparoscopy as compared with three (7.5%) major complications in the laparotomy group. Superficial wound infection was the most common (20%) infection in laparotomy patients while vaginal cuff cellulitis occurred in 10% of laparoscopy patients. Late (>42 days) postoperative complications were almost equally frequent (20.0 and 22.5%) in both groups. Lower extremity lymph edema or pelvic lymph cyst was found in 12.5% of all cases. As a result of surgical staging the disease of 6 women (15%) in both groups was upgraded. CONCLUSIONS: Laparoscopic surgery is a viable alternative to traditional surgery in the management of endometrial cancer. The surgical outcome is similar in both cases. In laparoscopic procedures the operation time is longer but the postoperative recovery time shorter than in laparotomy. Severe complications were limited in both groups, while wound infections can be avoided using laparoscopy.