Impact of hospital type and treatment on long-term survival among patients with FIGO Stage IIIC epithelial ovarian cancer: follow-up through two recurrences and three treatment lines in search for predictors for survival.

The purpose of this study was to investigate the impact of hospital type determined at primary treatment and find possible predictors of survival in a cohort of patients with advanced epithelial ovarian cancer (EOC) who recurred twice and received three lines of treatment during eight-year follow-up. Using the Norwegian Cancer Registry, the authors identified 174 women with FIGO Stage IIIC EOC diagnosed in 2002. First-line treatment consisted of up-front debulking surgery and chemotherapy, received in either a teaching hospital (TH, n = 84) or a non-teaching hospital (NTH, n = 90). After recurrence all patients in Norway are equally consulted at TH. Survival determined for three time intervals (TI): TI-1, from end date of first-line treatment to first recurrence or death, TI-2, from beginning of second-line treatment until second recurrence or death, and TI-3, from beginning of third-line treatment to death or end of follow-up. Extensive surgery carried out in TH followed by at least six cycles of platinol-taxan chemotherapy resulted in longer survival in the TH group during TI-1. Altogether, the majority of those who receive treatment for recurrences were primary better debulked with following platinol-taxane chemotherapy. Survival in TI-2 was influenced by platinol-sensitivity. During TI-3 the majority (96%) had good performance status and their mean age at primary diagnosis at either hospital type was 57 years. Extensive primary surgery at TH, platinol sensitivity, age, and performance status were predictors of survival in this cohort.

Fertility and gonadal function after adjuvant therapy in women diagnosed with a malignant ovarian germ cell tumor (MOGCT) during the "cisplatin era".

PURPOSE: By self-report and serum levels of anti-Mullerian hormone (AMH) this study aims to assess post-treatment fertility after modern treatment of women with malignant ovarian germ cell tumors (MOGCT). PATIENTS AND METHODS: In 2013 a questionnaire-based survey was performed in 61 MOGCT patients diagnosed at age <40years from 1980-2009. Forty-nine of them also attended the out-patient clinic. The event of first post-treatment pregnancy ("fertility") was documented as cumulative estimates for all 61 patients and within each of 4 treatment groups: Group 1: Surgery only (n=10); Group 2: ≤3cycles of cisplatin-based chemotherapy (CBCT) (n=20); Group 3: >3cycles of CBCT (n=15) and Group 4: other adjuvant treatment (n=16). AMH was determined in 22 women <40years at survey. Statistics were based on Kaplan Meier procedure, log-rank test and a significance level p<0.05. RESULTS: At least one post-treatment pregnancy was reported by 34 of 39 MOGCT survivors who attempted motherhood after treatment. The 15-year cumulative post-treatment fertility estimate was 28% (95% CI: 26-30) for all 61 survivors and was significantly higher in patients treated with 3 or fewer cycles of CBCT (53% [95% CI: 50-55]) than those treated with more than 3cycles (20% [95% CI: 17-22]) (P=0.03). Of 22 AMH levels, two were <3pmol/l, with one women being pregnant at survey. CONCLUSION: After fertility-sparing surgery and modern cisplatin-based chemotherapy, fertility is preserved in most MOGCT survivors though dependent on the number of cycles. AMH's role as a biomarker of gonadal function seems promising but requires further research.

Malignant ovarian germ cell tumors: presentation, survival and second cancer in a population based Norwegian cohort (1953-2009).

PURPOSE: To quantify and compare survival in women with malignant ovarian germ cell tumors (MOGCTs) in Norway before and after the introduction of cisplatin-based chemotherapy (around 1980), and to explore the association between different types of treatment and the development of a second cancer. PATIENTS AND METHODS: We identified 351 patients diagnosed with MOGCTs from 1953 to 2009 in the Cancer Registry of Norway. Ovarian cancer-specific survival was calculated separately for patients diagnosed before and after 1980. Patients were divided into subgroups by histological subtype (pure dysgerminoma, malignant teratoma, other MOGCTs) and extent of disease (localized and metastatic). We estimated the cumulative incidence of a second cancer in 10-year MOGCT survivors. Kaplan-Meier estimates were used, and p<0.05 was considered significant. RESULTS: 20-Year ovarian cancer-specific survival increased from 59% (95% CI 51% to 66%) before 1980 to 88% (95% CI 83%-93%) thereafter. Significant improvement was observed in all subgroups. No second cancer was diagnosed in any of 31 10-year MOGCT survivors treated with surgery only; second cancer was diagnosed in 23 of 139 patients who underwent cytotoxic treatment (98 radiotherapy ± chemotherapy, 41 chemotherapy only; p=0.08). Patients aged >50 years had a significantly poorer ovarian cancer-specific survival than younger patients (HR=5.98, 95% CI 3.39-10.57) after adjustment for histological subtype and stage at presentation. Our results favor the treatment of patients with metastatic MOGCTs at large cancer centers. CONCLUSION: Today women with MOGCTs have an excellent prognosis if treated according to modern therapeutic principles.

Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients.

BACKGROUND: The CALYPSO phase III trial compared CD (carboplatin-pegylated liposomal doxorubicin (PLD)) with CP (carboplatin-paclitaxel) in patients with platinum-sensitive recurrent ovarian cancer (ROC). Overall survival (OS) data are now mature. METHODS: Women with ROC relapsing > 6 months after first- or second-line therapy were randomised to CD or CP for six cycles in this international, open-label, non-inferiority trial. The primary endpoint was progression-free survival. The OS analysis is presented here. RESULTS: A total of 976 patients were randomised (467 to CD and 509 to CP). With a median follow-up of 49 months, no statistically significant difference was observed between arms in OS (hazard ratio = 0.99 (95% confidence interval 0.85, 1.16); log-rank P = 0.94). Median survival times were 30.7 months (CD) and 33.0 months (CP). No statistically significant difference in OS was observed between arms in predetermined subgroups according to age, body mass index, treatment-free interval, measurable disease, number of lines of prior chemotherapy, or performance status. Post-study cross-over was imbalanced between arms, with a greater proportion of patients randomised to CP receiving post-study PLD (68%) than patients randomised to CD receiving post-study paclitaxel (43%; P < 0.001). CONCLUSION: Carboplatin-PLD led to delayed progression and similar OS compared with carboplatin-paclitaxel in platinum-sensitive ROC.

First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)--a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG.

BACKGROUND: The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel. PATIENTS AND METHODS: We carried out a prospectively randomized phase III study comparing carboplatin plus paclitaxel (TC; area under the curve 5 and 175 mg/m(2)) with the same combination and epirubicin (TEC; 75 mg/m(2) i.v.). Between March 1999 and August 2001, 887 patients with epithelial ovarian, tubal or peritoneal cancer International Federation of Gynecology and Obstetrics stages IIB-IV were randomized to receive either TC (442 patients) or TEC (445 patients). RESULTS: Median time to progression was 16.4 months in the TEC arm and 16.0 months in the TC arm (hazard ratio 0.99; 95% confidence interval [CI]: 0.9-1.2). Median overall survival time was 42.4 months for the TEC arm and 40.2 for the TC arm (hazard ratio 0.96; 95% CI: 0.8-1.1). Grade 3/4 hematologic toxic effects and most grade 3/4 non-hematologic toxic effects were more frequent in the TEC arm. Accordingly, a quality-of-life analysis showed inferiority of TEC versus TC. CONCLUSION: The addition of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer.

Improved 5-year disease-free survival for FIGO stage I epithelial ovarian cancer patients without tumor rupture during surgery.

OBJECTIVE: To investigate the impact of perioperative capsule rupture on disease-free survival (DFS) and cancer-specific survival (CSS) in patients with FIGO stage I epithelial ovarian cancer (EOC I). METHODS: This prospective population-based study enrolled all 279 patients with EOC I diagnosed in Norway between 2002 and 2004. All patients underwent primary surgery. The data were collected from notification reports to the Norwegian Cancer Registry and included medical, surgical and histopathological records. Kaplan-Meier plots were used to show differences in DFS and CSS. Cox regression analyses were used to show the effect of prognostic factors on survival, expressed as hazard ratios (HRs). RESULTS: Significantly more patients in the capsule rupture group (Cr group) had clear cell tumors (28%) than in the FIGO stage IA and IB (AB group: 14%) groups, and the FIGO stage IC (C group: 17%; p<0.05) group. Despite adjuvant chemotherapy (AC), these patients had a poor 5-year DFS, 94% in the non-AC group and 81% in the AC group (p<0.01). After five years of follow-up, there was a lower DFS among patients in the Cr group (79%) and the C group (81%), compared with patients in the AB group (91%; p<0.05). Independent prognostic factors at the time of diagnosis were grade, histological type, ascites, adhesions, performance status, CA125 and DNA ploidy. After correcting for the four most important prognostic factors (grade, histological type, ascites, and DNA ploidy), the HR for recurrence was 4.0 (95% CI 1.3-12.7; p<0.05) for the Cr group and 1.8 (95% CI 0.5-6.1; p=0.3) for the C group, compared with the AB group. CONCLUSIONS: Improvement was observed in the 5-year DFS for EOC I patients without tumor rupture during surgery compared with those with tumor rupture. Since AC did not improve the long-term DFS and CSS rates, it is of utmost importance that surgeons avoid tumor rupture during surgery.

Diagnosis and treatment of borderline ovarian neoplasms "the state of the art".

The 5-year survival for women with Stage-I borderline tumours (BOT) is favourable, about 95-97%, but the 10-year survival is only between 70 and 95%, caused by late recurrence. The 5-year survival for Stage II-III patients is 65-87%. Standard primary surgery includes bilateral SOEB, omentectomy, peritoneal washing and multiple biopsies. Second cytoreductive surgery is recommended for patients with recurrent disease. Adjuvant postoperative therapy is not indicated in Stage-I diploid tumors. Occasional responses to chemotherapy have been reported in advanced BOTs but no study has shown improved survival. Recently a new theory has been developed describing a subset of S-ovarian cyst adenomas that evolve through S-BOT to low-grade carcinoma. A more correct staging procedure, classification of true serous implants and agreement on the contribution to stage of the presence of gelatinous ascites in mucinous tumours may in the future change the distribution of stage and survival data by stage for women with BOT. Independent prognostic factors in patients with epithelial ovarian BOT without residual tumour after primary surgery are DNA-ploidy, international FIGO-stage, histologic type and patient age. Studies on other molecular markers have not yet uncovered a reliable prediction of biologic behaviour, however, there is hope that future studies of genetics and molecular biology of these tumours will lead to useful laboratory tests. Future questions to be addressed in this review include the following: Have patients with borderline tumours in general been over-treated and how should these patients be treated? How to define the high-risk patients? In which group of patients is fertility-sparing surgery advisable and, do patients with borderline tumours benefit from adjuvant treatment?

Expression of matrix metalloproteinase-2 in serous borderline ovarian tumors is associated with noninvasive implant formation.

OBJECTIVE: To investigate matrix metalloproteinase (MMP) proteolytic and vascular endothelial growth factor (VEGF) and receptor (VEGFR-1, VEGFR-2) angiogenetic capacity in serous borderline ovarian tumors (S-BOTs) for women with and without noninvasive implants. METHODS: The population was made up of 99 patients with S-BOTs as the primary diagnosis between 1985 and 1995, 44 of whom had noninvasive implants and 55 without implants. MMP-2, MMP-14, the type-2 tissue inhibitor of MMPs (TIMP-2), and VEGF and receptors (VEGFR-1, VEGFR-2) were examined by immunhistochemistry. RESULTS: Strong positive (+++) MMP-2 staining was found more frequently in women with primary S-BOTs and noninvasive implants (76%) than in those without implants (53%; p < 0.05). In contrast, staining for MMP-14 and TIMP-2 was not significantly different in the two groups. Furthermore, expression of MMP-2, MMP-14, and TIMP-2 was similar in primary tumors and in their noninvasive implants. Most tumors in both groups had no VEGF expression (84% in the noninvasive implant group and 82% in the group without implants), while moderate (++) to strong (+++) expression of VEGFR-1 and VEGFR-2 was detected in 79% and 94% of the two tumor groups, with no significant difference between the groups. CONCLUSIONS: Enhanced MMP-2 was seen in primary S-BOT with noninvasive implants. The presence of noninvasive implants was prognostic for disease-free survival.

Primary surgery for ovarian cancer.

AIM: Review studies on survival outcomes for all survival treatment methods of primary ovarian cancer. METHODS: This presentation is based on systematic literature search in Pubmed, Medline, Cochrane and Internet addresses for treatment protocols. RESULTS: Major controversies still exist on what constitutes optimal surgical staging in a patient with early-stage ovarian cancer and what is optimal surgical management for high-risk patients. Several large retrospective studies consistently identify the size of the largest residual disease after primary cytoreductive surgery as an independent determinant of prognosis, but the size limit of residual disease that needs to be fulfilled for cytoreduction to have effect on survival is not identified. The effect of neoadjuvant chemotherapy in advanced ovarian cancer is uncertain. A large prospective randomized study is initiated for assessing the role of neoadjuvant chemotherapy. The survival rate is better for patients treated at teaching hospitals compared with non-teaching hospitals. CONCLUSION: This systematic review demonstrates the need for more studies on survival outcomes for all surgical treatment methods of primary ovarian cancer assessed in this report.

Improved short-term survival for advanced ovarian, tubal, and peritoneal cancer patients operated at teaching hospitals.

The aim of this study was to study the impact of hospital level and surgical skill on short-term survival of advanced ovarian, tubal, and peritoneal cancer patients in a prospective population-based study. All 198 women with a diagnosis of advanced epithelial invasive ovarian, tubal, and peritoneal cancer in Norway who underwent surgery during 2002 were included in this study. The data were derived from notifications to the Norwegian Cancer Registry and from medical, surgical, and histopathologic records. The hospitals were grouped into teaching and nonteaching hospitals (NTH), and the operating physicians were classified according to specialty (specialist gynecologist, gynecologist, and surgeon). The follow-up period was from 455 to 820 days. The short-term survival at 450 days was 79% for women operated at teaching hospitals (TH) and 62% at NTH (P= 0.02). After simultaneous adjustment for seven prognostic factors and residual disease, the risk of death within 600 days at NTH was unchanged compared to TH, hazard ratio 1.83. The women operated on by specialist compared to general gynecologists had a 20% increased short-term survival (P < 0.0001). TH and specialist gynecologists achieved better short-term survival of patients operated for advanced ovarian, tubal, and peritoneal cancer. Centralization and specialization of ovarian cancer surgery might improve the outcome for this patient group.

Prognostic factors in ovarian carcinoma stage III patients. Can biomarkers improve the prediction of short- and long-term survivors?

The aim of the study was to determine if biomarker expression could help discriminate between short-term and long-term survivors in women with advanced ovarian cancer. Fifty-one patients with stage III ovarian cancer were selected for the study, which included 28 short-term survivors (death from ovarian cancer within 18 months) and 23 long-term survivors (alive for more than 5 years). There was no difference between the two groups with respect to FIGO substage, age, World Health Organization score, and first-line platinum therapy. Classic clinical pathologic parameters were examined together with p53, Bcl-2, Ki-67, PDGFRalpha, P-glycoprotein, BRCA1, and DNA ploidy. Immunohistochemistry was used for scoring biomarker expression and image cytometry for DNA ploidy. All patients had primary debulking surgery followed by first-line platinum therapy. On multivariate analysis, the presence of ascites, debulking surgery and repeat laparotomy, clear-cell histology, elevated CA125, and high Ki-67 score were all found to be of prognostic importance. The long-term survivors were characterized by primary optimal cytoreduction surgery (<1 cm residual disease), attempt at maximal tumor debulking by experienced gynecological oncologic surgeons, and the absence of ascites. Normal CA125 level before platinum therapy and negative Ki-67 expression also predicted a more favorable prognosis.

Symptoms and referral of women with epithelial ovarian tumors.

OBJECTIVE: To study referral to hospital units and the clinical characteristics of women with epithelial ovarian tumors in a prospective, population-based study. METHODS: Clinical information on all women diagnosed with epithelial invasive (n=486) and borderline ovarian tumors (n=137) in Norway during 2002 was derived from notifications to the Cancer Registry of Norway and medical, surgical and histopathological records. RESULTS: Sixty-one percent of women with invasive ovarian tumors were initially referred to gynecology units. The 38% of women referred to surgical and medical units were more likely to have symptoms as 'bowel irregularity', 'pain outside the abdominal cavity', 'persisting fatigue' and 'respiratory difficulties'. These women were older, had lower performance status and had a delay in treatment of 20 and 24 days respectively compared to 11 at gynecology units. CONCLUSION: Greater awareness of the symptoms of ovarian cancer might lead to earlier diagnosis and treatment and thus possibly improve survival.

Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer.

Two independent and consecutive randomized clinical trials, conducted by the American Gynecological Oncology Group and by an European-Canadian Intergroup, have shown superiority, in clinical response rate, progression-free survival, and overall survival, of a cisplatin-paclitaxel regimen over cisplatin-cyclophosphamide given as first-line chemotherapy for women with advanced epithelial ovarian cancer. The results of these studies, published with a median follow-up of about 3 years, have been updated with a 6.5-year follow-up: In each case, an 11% absolute gain in survival favoring the paclitaxel arm is shown; this advantage remains both statistically and clinically significant and supports a role for paclitaxel in frontline chemotherapy for advanced ovarian cancer.

First-line treatment of ovarian cancer FIGO stages IIb-IV with paclitaxel/epirubicin/carboplatin versus paclitaxel/carboplatin.

The objective of this study was to compare the safety and efficacy of carboplatin plus epirubicin and paclitaxel (TEC) to carboplatin and paclitaxel (TC), in the treatment of epithelial ovarian, peritoneal, or tubal carcinoma. Between March 1999 and August 2001, 887 patients were randomized to receive six to nine cycles of paclitaxel (175 mg/m2, 3 h intravenously) followed by carboplatin (AUC 5, Calvert formula) with or without epirubicin (75 mg/m2 intravenously prior to paclitaxel), on a 3-weekly schedule. The primary endpoint was progression-free survival. Demographic information: Residual disease <1 cm was reported on 41% of patients. At the end of treatment, 65% in the TEC and 55% in the TC arm had achieved a clinical complete response, and 18 and 25% a clinical partial response resulting in an overall response rate of 83% in the TEC and 80% in the TC arm, whereas 7 and 9% had progressive disease, respectively. The three-drug combination produced a markedly higher myelotoxicity, resulting in a higher frequency of febrile neutropenia (12.5% of the TEC and 1.5% of the TC patients) and a higher number of dose reductions and treatment delays. Cycle prolongation above seven days was seen in 7 and 5% of cycles in the TEC and TC arm, respectively. Stomatitis > or = grade 3 was also higher with TEC (4% TEC and 0.5% TC). Reductions in left ventricular ejection fraction of more than 15% after six courses were slightly more common with the TEC regimen (3% versus 1.5%), but the difference was not statistically significant (P = 0.2). In conclusion, treatment with the TEC combination produced a higher rate of complete responses than treatment with the TC combination. Toxicity was manageable. Long-term survival data are awaited.

Large-scale genomic instability predicts long-term outcome for women with invasive stage I ovarian cancer.

BACKGROUND: The objective was to evaluate the value of DNA ploidy using high-resolution image cytometry in predicting long-term survival of patients with early ovarian cancer. PATIENTS AND METHODS: A retrospective analysis of 284 cases with FIGO stage I ovarian carcinoma treated during the period 1982-1989 was performed. Clinical follow-up information was available for all patients. RESULTS: Patients with diploid and tetraploid tumors had a 10-year relapse-free survival of 95% and 89%, respectively, compared with 70% and 29% for polyploid and aneuploid tumors, respectively. DNA ploidy analysis was the strongest predictor of survival in multivariate analysis (diploid/tetraploid versus polyploid/aneuploid; relative hazard 9.0) followed by histological grade, including clear cell tumors in the group of poorly differentiated tumors (grade 1-2 versus grade 3 or clear cell; relative hazard 2.7), and FIGO stage (Ib/Ic versus Ia; relative hazard 2.0). In a stratified Kaplan-Meier analysis, patients with grade 1-2, diploid or tetraploid tumors had a 10-year relapse-free survival of 95%, forming a low-risk group. Patients with grade 3 or clear cell, diploid or tetraploid tumors had 10-year relapse-free survival of 86%, forming an intermediate-risk group, while all patients with aneuploid/polyploid tumors formed a high-risk group, with 10-year relapse-free survival of 34%. CONCLUSIONS: This study points to the importance of including DNA ploidy analysis by image cytometry when selecting patients with early ovarian cancer for adjuvant treatment after surgery.

Gestational trophoblastic tumors in Norway, 1968-1997: patient characteristics, treatment, and prognosis.

OBJECTIVES: The aim of this study was to give an overview of the Norwegian population of gestational trophoblastic tumors (GTT), diagnosed during 1968-1997 and treated with chemotherapy at the Norwegian Radium Hospital (NRH), with regard to patient characteristics, treatment, and prognosis. METHODS: The cases were grouped according to a modified version of the WHO scoring system. Staging was performed retrospectively according to the systems adopted by FIGO. Survival estimates were calculated by the method described by Kaplan and Meier. Cox regression models were used to find the best classification system with regard to prognosis (disease-free survival). RESULTS: A total of 141 cases, 106 invasive moles (IM) and 35 choriocarcinomas (CC), were diagnosed in Norway and treated with chemotherapy at the NRH in the period 1968-1997. Altogether, 56% of the patients were assigned to the low-risk category, 20% to the medium-risk category, and 15% to the high-risk category. Most cases were classified into the clinical stages I (69%) and III (23%). The overall 5-year survival rate was 96%. A more favorable prognosis was seen in patients diagnosed in the 1980s and 1990s compared with those diagnosed in the 1970s (P = 0.04). Five patients had progressive disease and died from the disease. Nine patients relapsed. The prognosis (disease-free survival) was more favorable for IM compared with CC (P < 0.01). The FIGO classification system seemed to be a better predictor of disease-free survival than the WHO scoring system. CONCLUSIONS: This study showed that the prognosis of patients with GTT improved in the 1980s and 1990s in Norway, and that the FIGO system might be the best predictor of disease-free survival.

A phase II study of weekly paclitaxel in platinum and paclitaxel-resistant ovarian cancer patients.

OBJECTIVE: In platinum-resistant ovarian cancer weekly paclitaxel has shown an equal efficiency and better toxicity profile compared to three-weekly paclitaxel in platinum-resistant ovarian cancer. We wanted to study response rate, response duration and toxicity in platinum-resistant tumors with emphasis on tumors also resistant to three-weekly paclitaxel. MATERIAL AND METHODS: Fifty-seven patients with platinum-resistant disease, treated with weekly paclitaxel 80 mg/m2, 1-hour infusion, were evaluable for response and toxicity (Group A). Of these, 39 patients (Group B) had tumors resistant to paclitaxel as well. RESULTS: Overall response rate was 56% (12% CR, 44% PR, 19% SD, 25% PD) and 49% in group B: 5% CR, 44% PR, 23% SD, 28% PD. Median progression-free survival was 5.0 months and 4.0 months in group A and B, respectively. Median survival was 13.7 months in both groups. Toxicity was mild. Only two patients had grade 2 neutropenia and no neutropenic fever was recorded. No worsening in pre-existing neurotoxicity or hypersensitivity reactions was observed. CONCLUSION: Weekly administration of paclitaxel is associated with promising response rates in patients with platinum- and paclitaxel-resistant ovarian cancer. The treatment is well tolerated with non-cumulative hematologic and non-hematologic toxicity.

[Examination, treatment and follow-up of ovarian cancer in Norway]. / Utredning, behandling og etterkontroll av eggstokkreft i Norge.

BACKGROUND: In order to improve our knowledge about the medical examination, treatment and follow of cancer patients, suggestions have been put forward for a system for quality assurance of clinical data on cancer in Norway (Government White Paper 20: 1997). MATERIAL AND METHODS: In spring 2000, a questionnaire was sent to 41 gynaecological departments with focus on ovarian cancer patients. Four of the departments were regional cancer centres. RESULTS: All gynaecological departments answered the questionnaire. Standard gynaecological examination, vaginal ultrasonography and CA-125 determination were included in the diagnostic procedures in all departments. Some differences were detected: Cytological examination of pleural effusions as part of the staging procedure was not performed by all hospitals. In one health region, hospitals used a Risk of Malignancy Index for referring women with suspected malignant pelvic masses to a centralised gynaecologic oncology unit for primary surgery. Sixteen hospitals out of 37 operated on patients with FIGO stage I disease without performing lympadenectomy. When operating on suspected FIGO stage II-IV disease, three out of 22 local hospitals never performed surgery of the intestines in order to achieve optimal tumour reduction. All regional hospitals gave adjuvant chemotherapy to high-risk FIGO stage I patients. Standard treatment in advanced stages was paclitaxel/carboplatinum. Some hospitals participated in randomized trials on chemotherapy. Third-line treatment depended on the patient's condition, earlier toxicity and response. One regional centre preferred not to give any third-line chemotherapy. Only a few hospitals recorded the patient's performance status (WHO or Karnofsky's grading table) during the treatment and follow-up. Most of the gynaecological departments referred the patients to the regional hospital at the time of recurrence. About half of the outpatient departments gave a written report to the regional hospital. INTERPRETATION: There are differences between the hospitals in how they handle ovarian cancer patients. One cannot, however, determine from this inquiry what kind of medical examination, treatment and follow-up is best. An extended registration of ovarian cancer organised by the Cancer Registry of Norway will be started with the aim of providing reliable population-based data (the OVANOR project).

Long-term results from a phase II study of paclitaxel combined with doxorubicin in recurrent platinum refractory ovarian cancer.

BACKGROUND: There is still a need for newer non-cross-resistant agents and combinations to be tried in cases of failure after first line platinum-based therapy. Several agents have demonstrated activity after failure of platinum-containing regimens. Response rate in true platinum refractory disease up to 20% but with poor long-term survival, has been reported by single drug paclitaxel. In an effort to improve response rate and survival duration obtainable with single drug paclitaxel, we have combined paclitaxel with doxorubicin for the treatment of patients refractory to cisplatin-cyclophosphamide. PATIENTS AND METHODS: Between October 1994 and November 1996, 23 patients whereof 21 refractory to cisplatin-cyclophosphamide were enrolled for toxicity and survival analysis after receiving the combination doxorubicin 50 mg/m2 and paclitaxel 135 mg/m2 every third week for four courses. Responding patients continued on single drug paclitaxel 175 mg/m2 every third week until unacceptable toxicity or tumor progression occurred. RESULTS: The objective response rate (CR + PR) was 33%, 95% CI (14.6-57). The median duration of response was 8.5 months (range 4.0-62.5+) and the median overall survival was 15.5 months (range 4.0-63.5+). No serious toxicity was registered. CONCLUSION: Doxorubicin combined with paclitaxel could safely be administered using this schedule. This study shows that some patients obtaining CR can be rendered disease-free for a substantial period of time, sometimes five years or more. A median overall survival of 15.5 months with a 5-year survival probability of 15% is impressive. However, although responses can be induced in a significant number of patients, the survival figures remain poor.

Prognostic importance of degree of differentiation and cyst rupture in stage I invasive epithelial ovarian carcinoma.

BACKGROUND: Previous studies on prognostic factors in stage I invasive epithelial ovarian carcinoma have been too small for robust conclusions to be reached. We undertook a retrospective study in a large international database to identify the most important prognostic variables. METHODS: 1545 patients with invasive epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] stage I) were included. The records of these patients were examined and data extracted for univariate and multivariate analysis of disease-free survival in relation to various clinical and pathological variables. FINDINGS: The multivariate analyses identified degree of differentiation as the most powerful prognostic indicator of disease-free survival (moderately vs well differentiated hazard ratio 3.13 [95% CI 1.68-5.85], poorly vs well differentiated 8.89 [4.96-15.9]), followed by rupture before surgery (2.65 [1.53-4.56]), rupture during surgery (1.64 [1.07-2.51]), FIGO 1973 stage Ib vs Ia 1.70 [1.01-2.85]) and age (per year 1.02 [1.00-1.03]). When the effects of these factors were accounted for, none of the following were of prognostic value: histological type, dense adhesions, extracapsular growth, ascites, FIGO stage 1988, and size of tumour. INTERPRETATION: Degree of differentiation, the most powerful prognostic indicator in stage I ovarian cancer, should be used in decisions on therapy in clinical practice and in the FIGO classification of stage I ovarian cancer. Rupture should be avoided during primary surgery of malignant ovarian tumours confined to the ovaries.