Natural History of Stage IV Epithelial Ovarian Cancer

1999 ◽  
Vol 17 (3) ◽  
pp. 767-767 ◽  
Author(s):  
H. Bonnefoi ◽  
R. P. A'Hern ◽  
C. Fisher ◽  
V. Macfarlane ◽  
D. Barton ◽  
...  

PURPOSE: In this report we present the natural history, prognostic factors, and therapeutic implications of stage IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS: We reviewed 192 patients with stage IV EOC as defined in 1985 by the International Federation of Gynecology and Obstetrics. RESULTS: The site of stage IV–defining disease was cytologically positive pleural effusion in 63 patients, liver in 50 patients, lymph nodes in 26 patients, lung in six patients, other sites in 15 patients, and disease at multiple stage IV–defining metastatic sites in 32 patients. Surgery was performed before chemotherapy in 169 patients; 25 patients (14.8%) were left with only microscopic residual disease or less than 2 cm of macroscopic residual disease. The overall response rate to chemotherapy was 56%; the complete response rate was 18%. The median progression-free survival was 7.1 months, and the median overall survival was 13.4 months. The median overall survival of patients with positive pleural effusions only was 13.4 months as compared with 10.5 months for patients with visceral disease only, but this difference was not statistically significant. The 5-year survival rate was 7.6%, with only six patients surviving more than 5 years. Univariate and multivariate analysis showed that two parameters were associated with a shorter survival time: visceral involvement (lung or liver) and diagnosis before 1984. CONCLUSION: Patients with stage IV EOC initially respond to chemotherapy as often as those with less advanced disease, but the long-term prognosis is very poor. The size of residual disease is not a prognostic factor in this group of patients, and, therefore, the role of debulking surgery in these patients needs to be reconsidered.

2018 ◽  
Vol 28 (3) ◽  
pp. 453-458 ◽  
Author(s):  
Parvin Tajik ◽  
Roelien van de Vrie ◽  
Mohammad H. Zafarmand ◽  
Corneel Coens ◽  
Marrije R. Buist ◽  
...  

ObjectiveThe revised version of the International Federation of Gynaecology and Obstetrics (FIGO) staging system (2014) for epithelial ovarian cancer includes a number of changes. One of these is the division of stage IV into 2 subgroups. Data on the prognostic and predictive significance of this classification are scarce. The effect of neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) in relation to the subclassification of FIGO stage IV is also unknown.MethodsWe used data of the EORTC 55971 trial, in which 670 patients with previous stage IIIC or IV epithelial ovarian cancer were randomly assigned to PDS or NACT; 160 patients had previous stage IV. Information on previous FIGO staging and presence of pleural effusion with positive cytology were used to classify tumors as either stage IVA or IVB. We tested the association between stage IVA/IVB and survival to evaluate the prognostic value and interactions between stage, treatment, and survival to evaluate the predictive performance.ResultsAmong the 160 participants with previous stage IV disease, 103 (64%) were categorized as stage IVA and 57 (36%) as stage IVB tumors. Median overall survival was 24 months in FIGO stage IVA and 31 months in stage IVB patients (P = 0.044). Stage IVB patients treated with NACT had 9 months longer median overall survival compared with IVB patients undergoing PDS (P = 0.025), whereas in IVA patients, no significant difference was observed (24 vs 26 months, P = 0.48).ConclusionsThe reclassification of FIGO stage IV into stage IVA or IVB was not prognostic as expected. Compared with stage IVA patients, stage IVB patients have a better overall survival and may benefit more from NACT.


2008 ◽  
Vol 26 (1) ◽  
pp. 83-89 ◽  
Author(s):  
William E. Winter ◽  
G. Larry Maxwell ◽  
Chunqiao Tian ◽  
Michael J. Sundborg ◽  
G. Scott Rose ◽  
...  

Purpose To identify factors predictive of poor prognosis in a similarly treated population of women with stage IV epithelial ovarian cancer (EOC). Patients and Methods A retrospective review of 360 patients with International Federation of Gynecology and Obstetrics stage IV EOC who underwent primary surgery followed by six cycles of intravenous platinum/paclitaxel was performed. A proportional hazards model was used to assess the association of potential prognostic factors with progression-free survival (PFS) and overall survival (OS). Results The median PFS and OS for this group of stage IV ovarian cancer patients was 12 and 29 months, respectively. Multivariate regression analysis revealed that histology, malignant pleural effusion, intraparenchymal liver metastasis, and residual tumor size were significant prognostic variables. Whereas patients with microscopic residual disease had the best outcome, patients with 0.1 to 1.0 cm residual disease and patients with 1.1 to 5.0 cm residual disease had similar PFS and OS. Patients with a residual size more than 5 cm had a diminished PFS and OS when compared with all other groups. Median OS for microscopic, 0.1 to 5.0 cm, and more than 5.0 cm residual disease was 64, 30, and 19 months, respectively. Conclusion Patients with more than 5 cm residual disease have the shortest PFS and OS, whereas patients with 0.1 to 1.0 and 1.1 to 5.0 cm have similar outcome. These findings suggest that ultraradical cytoreductive procedures might be targeted for selected patients in whom microscopic residual disease is achievable. Patients with less than 5.0 cm of disease initially and significant disease and/or comorbidities precluding microscopic cytoreduction may be considered for alternative therapeutic options other than primary cytoreduction.


2016 ◽  
Vol 26 (5) ◽  
pp. 906-911 ◽  
Author(s):  
Luis M. Chiva ◽  
Teresa Castellanos ◽  
Sonsoles Alonso ◽  
Antonio Gonzalez-Martin

ObjectiveThe objective of this review was to try to determine by searching in the literature what is the survival in patients with advanced ovarian cancer after a primary debulking with minimal macroscopic residual disease (MMRD; 0.1–10 mm). Additionally, this review aimed to explore the survival in patients with residual disease from 0.1 to 0.5 cm.MethodsA retrospective search was accomplished in the PubMed database looking for all English-language articles published between January 1, 2007 and December 31, 2014, under the following search strategy: “ovarian cancer and cytoreduction” or “ovarian cancer and phase III trial”. We selected those articles that contain information on both percentage of MMRD (0.1–1 cm) and median overall survival (OS) in this subset of patients with stage III to stage IV ovarian cancer after primary debulking surgery.ResultsThirteen publications were obtained including information of a total 11,999 patients with stage III to stage IV ovarian cancer. Five thousand thirty-seven patients (42%) had MMRD after the primary debulking (0.1–1 cm). Median overall survival in patients with MMRD was 40 months and disease-free survival (DFS) was 16 months. This group of patients obtained an advantage of 10 months in OS (40 vs 30 m) and 4 months in DFS (16 vs 12 m) compared with the group with suboptimal debulking (P < 0.001). Compared with the group of complete resection, patients with minimal macroscopic residuum showed a significant inferior median OS and DFS of 30 months and 14 months, respectively (OS, 70 vs 40 m; DFS, 30 vs 16 m) (P < 0.001). The group of residual disease of 0.1 to 0.5 cm reached a median survival of 53 months.ConclusionsPatients with ovarian cancer with MMRD after primary surgery obtain a modest but significant advantage in survival (10 months) over suboptimal patients. Patients with macroscopic residual disease (0.1–0.5 cm) obtain a better survival (53 months) than those with more than 0.5 to 1 cm. We propose that they should be classified as a different prognostic group.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16512-e16512
Author(s):  
V. Kolev ◽  
S. Mironov ◽  
O. Mironov ◽  
C. Moskowitz ◽  
N. M. Ishill ◽  
...  

e16512 Background: It has been hypothesized and shown in animal studies that the supradiaphragmatic lymph nodes serve as the principal nodes for lymphatic drainage of the entire peritoneal cavity. The purpose of this study was to determine the prognostic significance of enlarged supra-diaphragmatic nodes noted on preoperative computed tomography (CT) scan in patients with advanced epithelial ovarian cancer (EOC). Methods: We performed a retrospective chart review of all patients (pts) with FIGO stage III and IV EOC who had preoperative CT scans of the supradiaphragmatic region and primary cytoreductive surgery at our institution between 1997 and 2004. All scans were retrospectively reviewed by one board-certified radiologist (SM). To evaluate survival, Kaplan-Meier methods were used, with log rank Pvalues for comparisons. Results: A total of 212 eligible pts who underwent attempted primary cytoreduction followed by platinum-based systemic chemotherapy were identified for evaluation. With a median follow-up time of 52 mos, there were 135 deaths and a median overall survival of 48 mos (95% CI: 44–53). Of the 212 pts, 44 (21%) had supradiaphragmatic adenopathy with nodes >1 cm, while 168 (79%) did not have adenopathy in this distribution. None of the 44 pts with adenopathy had the enlarged nodes removed at primary cytoreduction. The median survival was 49 mos for pts with and 48 mos for patients without adenopathy (p = 0.46). In total, 155 (73%) patients underwent optimal cytoreduction (residual disease ≤ 1 cm). In the optimally cytoreduced pts, the median survival for the 125 pts without supradiaphragmatic adenopathy was 52 mos (95%CI: 45–59) compared to 51mos (95%CI: 41–58) for the 30 pts with supradiaphragmatic adenopathy (p = 0.33). Conclusions: Although a previous study has shown that supradiaphragmatic adenopathy was associated with poorer overall survival in EOC patients, our study did not confirm these findings. In our study, enlarged supradiaphragmatic nodes noted on preoperative CT scan did not have significant prognostic impact and therefore their clinical significance remains uncertain. No significant financial relationships to disclose.


2012 ◽  
Vol 22 (6) ◽  
pp. 987-992 ◽  
Author(s):  
Augusto Pereira ◽  
Tirso Pérez-Medina ◽  
Javier F. Magrina ◽  
Paul M. Magtibay ◽  
Isabel Millan ◽  
...  

ObjectiveTo evaluate the therapeutic role of pelvic and aortic lymphadenectomy in patients with epithelial ovarian cancer (EOC) and positive nodes (stages IIIC and IV).MethodsRetrospective chart review. Data from all consecutive patients with EOC and positive retroperitoneal lymph nodes (stage IIIC and IV) in Mayo Clinic from 1996 to 2000 were included. To evaluate the impact of nodal metastases, the extent of lymphadenectomy was compared according to the number of nodes removed and positive nodes resected. Multivariable Cox regression and Kaplan-Meier survival curves were used for analysis.ResultsThe median number of nodes removed was 31 (pelvic, 21.5, and aortic, 10), and the median number of positive nodes was 5. The 5-year overall survival was 44.8%. On multivariate analysis, only the extent of peritoneal metastases before surgery was a significant factor for survival (P = 0.001 for stage IIIC and P = 0.004 for stage IV). Analysis of 83 patients with advanced peritoneal disease more than 2 cm demonstrated before debulking, removal of more than 40 lymph nodes was a significant prognostic factor for overall survival (hazard ratio, 0.52; P = 0.032; 95% confidence interval, 0.29–0.35). In 29 patients with advanced peritoneal disease and no residual disease after debulking, removal of more than 10 positive was a factor for survival.ConclusionsThere was a survival benefit in patients with EOC with advanced peritoneal disease more than 2 cm before debulking when more than 40 lymph nodes were removed. There was an additional survival benefit in those patients with no residual disease after debulking when more than 10 positive nodes were removed.


2020 ◽  
Vol 30 (6) ◽  
pp. 888-892 ◽  
Author(s):  
Simone Koole ◽  
Ruby van Stein ◽  
Karolina Sikorska ◽  
Desmond Barton ◽  
Lewis Perrin ◽  
...  

BackgroundThe addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery improves recurrence-free and overall survival in patients with FIGO stage III ovarian cancer who are ineligible for primary cytoreductive surgery. The effect of HIPEC remains undetermined in patients who are candidates for primary cytoreductive surgery.Primary objectiveThe primary objective is to evaluate the effect of HIPEC on overall survival in patients with FIGO stage III epithelial ovarian cancer who are treated with primary cytoreductive surgery resulting in no residual disease, or residual disease up to 2.5 mm in maximum dimension.Study hypothesisWe hypothesize that the addition of HIPEC to primary cytoreductive surgery improves overall survival in patients with primary FIGO stage III epithelial ovarian cancer.Trial designThis international, randomized, open-label, phase III trial will enroll 538 patients with newly diagnosed FIGO stage III epithelial ovarian cancer. Following complete or near-complete (residual disease ≤2.5 mm) primary cytoreduction, patients are randomly allocated (1:1) to receive HIPEC or no HIPEC. All patients will receive six courses of platinum-paclitaxel chemotherapy, and maintenance PARP-inhibitor or bevacizumab according to current guidelines.Major eligibility criteriaPatients with FIGO stage III primary epithelial ovarian, fallopian tube, or primary peritoneal cancer are eligible after complete or near-complete primary cytoreductive surgery. Patients with resectable umbilical, spleen, or local bowel lesions may be included. Enlarged extra-abdominal lymph nodes should be negative on FDG-PET or fine-needle aspiration/biopsy.Primary endpointThe primary endpoint is overall survival.Sample sizeTo detect a HR of 0.67 in favor of HIPEC, 200 overall survival events are required. With an expected accrual period of 60 months and 12 months additional follow-up, 538 patients need to be randomized.Estimated dates for completing accrual and presenting resultsThe OVHIPEC-2 trial started in January 2020 and primary analyses are anticipated in 2026.Trial registrationClinicalTrials.gov:NCT03772028


2015 ◽  
Vol 25 (2) ◽  
pp. 208-213 ◽  
Author(s):  
Ahmed Numan Alniaimi ◽  
Kristin Demorest-Hayes ◽  
Vinita M. Alexander ◽  
Songwon Seo ◽  
David Yang ◽  
...  

ObjectiveDespite improvements in surgery and chemotherapy, ovarian cancer remains a deadly disease in need of improved therapies. We have previously shown that Notch1 intracellular domain (NICD) is highly expressed in ovarian cancer. We have also shown that NICD inhibition can lead to growth arrest in ovarian cancer cells. The objective of the current study was to delineate whether NICD expression correlates with prognosis of women with ovarian cancer.MethodsAfter the institutional review board approval, patients with a diagnosis of primary ovarian cancer between the years 2001 and 2007 who underwent surgery at our institution were identified. Paraffin blocks from the primary ovarian tumor were analyzed, and core samples were obtained to build a tissue microarray. Cytoplasmic NICD expression was assessed by quantitative immunofluorescent morphometry using the automated quantitative analysis system. These results were correlated with clinical and pathology data retrieved from the patient records.ResultsWe identified 328 patients with primary ovarian cancer during this period. Seventeen percent of patients had stage I, 11% had stage II, 59% had stage III, and 13% had stage IV disease. Most patients (70%) had papillary serous histology, and most (86%) underwent optimal debulking to less than 1 cm of residual disease. High NICD expression was found to correlate strongly with low overall survival (P = 0.001). This effect remained in multivariate analysis (P = 0.023).ConclusionsHigh expression of NICD in the primary tumor of women with ovarian cancer is an independently poor prognostic factor for overall survival. Further research into the therapeutic inhibition of the Notch1 pathway is warranted.


2007 ◽  
Vol 17 (5) ◽  
pp. 986-992 ◽  
Author(s):  
M. O. Nicoletto ◽  
S. Tumolo ◽  
R. Sorio ◽  
G. Cima ◽  
L. Endrizzi ◽  
...  

The purpose of this study was to compare long-term survival in first-line chemotherapy with and without platinum in advanced-stage ovarian cancer. From July 1987 to November 1992, 161 untreated patients with FIGO stage III–IV epithelial ovarian cancer were randomized: 81 patients received no platinum and 80 received platinum combination. Residual disease after surgery was <2 cm in 61 patients without platinum, 59 with platinum. Median age was 58 years in nonplatinum arm and 55 years in platinum arm (range: 15–73). Complete and partial responses were 51% and 10% for nonplatinum arm and 51% and 8% for platinum arm, respectively (P= 0.7960). Stable disease was observed in 18% of patients in nonplatinum arm and 15% of patients in platinum arm and progression in 20% of nonplatinum- and 21% of platinum-treated cases. Ten-year disease-free survival was 37% for therapy without platinum and 31% for platinum combination (P= 0.5679); 10-year overall survival was 23% without platinum and 31% with platinum combination (P= 0.2545). Fifteen-year overall survival showed a trend of short duration in favor of platinum (P= 0.0678). Relapses occurred after 60 months in ten patients (seven with and three without platinum). The overall and disease-free survivals at 5, 10, and 15 years show no statistically significant long-term advantage from the addition of cisplatin; however, there is a slight trend in its favor.


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